Journal articles on the topic 'Four step technique to be free from addiction'

Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus–action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian–instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.

We introduce here a new two-step derivate-free inverse simultaneous iterative method for estimating all roots of nonlinear equation. It is proved that convergence order of the newly constructed method is four. Lower bound of the convergence order is determined using Mathematica and verified with theoretical local convergence order of the method introduced. Some nonlinear models which are taken from physical and engineering sciences as numerical test examples to demonstrate the performance and efficiency of the newly constructed modified inverse simultaneous methods as compared to classical methods existing in literature are presented. Dynamical planes and residual graphs are drawn using MATLAB to elaborate efficiency, robustness, and authentication in its domain.

This descriptive cross sectional study was conducted to identify the teachers’ & students’ views according to extracurricular activities influencing academic performance of undergraduate medical students. The study period was July 2017 to June 2018.The study was carried out among four phases of undergraduate medical students & teachers of basic science, para clinical & clinical subjects of four (04) government & four (04) non-government selected medical colleges of Dhaka & outside Dhaka. Medical colleges were selected purposively & convenience sampling technique was adopted for data collection. A self-administered semi-structured questionnaire using five points Likert scale were administered on 58 teachers & 1020 students to collect data & an interview schedule was used to conduct in-depth interviews with 15 medical teachers. Study revealed that according to views of the medical students, factors like drug addiction 922(90.6%) & student politics 835(82.0%) were negatively influencing academic performance of undergraduate medical students. On the other hand, factors like indoor-outdoor games 791(77.7%), cultural activities 611(60.0%) & social activities 658(64.7%) were positively influencing on their academic performance. Findings of the students’ views were consistent with the teachers’ views. In-depth interview of the teachers revealed that students should take part in extra-curricular activities alongside their study. But it should be in a balanced way so that they do not hamper their study. Teachers should encourage students to participate in extra-curricular activities. Study recommended that medical campus should be kept free from the unhealthy student politics. Study also recommended to prevent drug addiction, the parents should be aware & the college authority should have adequate monitoring in the student hostels & should strictly implement any measure if required. Bangladesh Journal of Medical Education Vol.11(1) 2020: 32-42

The derivation of Runge–Kutta pairs of orders five and four that effectively uses six stages per step is considered. The coefficients provided by such a method are 27 and have to satisfy a system of 25 nonlinear equations. Traditionally, various solutions have been tried. Each of these solutions makes use of some simplified assumptions and offers different families of methods. Here, we make use of the most celebrated family to appear in the literature, where we may use as the last stage the first function evaluation from the next step (FSAL property). The family under consideration has the advantage of being solved explicitly. Actually, we arrive at a subsystem where all the coefficients are found with respect to five free parameters. These free parameters are adjusted (trained) in order to deliver a pair that outperforms other similar pairs of orders 5(4) in Keplerian type orbits, e.g., Kepler, perturbed Kepler, Arenstorf orbit or Pleiades. The training uses differential evolution technique. The finally proposed pair has a remarkable performance and offers on average more than a digit of accuracy in a variety of orbits.

A number of viruses cause considerable yield loss and quality deterioration in garlic. Root meristems of virus infected plants are known to be free from detectable viruses. This potentiality could be exploited to obtain virus free clones at a high frequency by culturing excised root meristems in vitro. We have developed efficient methods of direct and somatic embryo derived shoot regeneration from root meristems of garlic. The objectives of this work were to detect viruses infecting Bangladeshi and Japanese garlic clones and find an easy and efficient method of eliminating the viruses for the improvement of both yield and quality of garlic. At first, we confirmed the presence of detectable viruses in three Bangladeshi and one Japanese clones. The clones were infected with four different types of viruses: Garlic viruses (GarVs), Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), and Garlic common latent virus (GCLV). To eliminate those viruses, as per our previous method, root meristems were cultured on MS medium supplemented with 1.0 µM NAA and 10.0 µM BA. Shoot primordia developed from the cultured explants within 1 month. The regenerated individual shoot buds (2-5 mm) were separated from the mother explants and transferred to growth regulators free medium. RT-PCR confirmed that the viruses present in the mother garlic plants were absent in the shoots found after two-step culture. The regenerated shoots were rooted on growth regulator free medium and transferred to pots. Results indicated that the plants remained free from LYSV. Virus elimination through root meristem culture emerged as an efficient novel technique for the eradication of multiple viruses as confirmed by RT-PCR in this study. This technique has the potential for the production and supply of virus free propagules (plants/bulblets) for the yield and quality improvement of garlic.Progressive Agriculture 28 (2): 55-63, 2017

Numerov-type methods using four stages per step and sharing sixth algebraic order are considered. The coefficients of such methods are depended on two free parameters. For addressing problems with oscillatory solutions, we traditionally try to satisfy some specific properties such as reduce the phase-lag error, extend the interval of periodicity or even nullify the amplification. All of these latter properties come from a test problem that poses as a solution to an ideal trigonometric orbit. Here, we propose the training of the coefficients of the selected family of methods in a wide set of relevant problems. After performing this training using the differential evolution technique, we arrive at a certain method that outperforms the other ones from this family in an even wider set of oscillatory problems.

e15044 Background: Circulating tumor DNA (ctDNA), a cell-free DNA (cfDNA) present in the plasma of cancer patients, originates from cancer cells and serves as a crucial biomarker during cancer treatment. Despite its importance, the current limit of detection (LoD) of conventional ctDNA assays is suboptimal (0.01%; 10-4) for detecting ctDNA from microscopic residual and recurrent cancer tissues. To address this, we integrated two cutting-edge techniques: whole-genome sequencing (WGS) of primary cancer tissue (a mutation capture step) and duplex DNA sequencing-based cfDNA sequencing (mutation recapture steps). Methods: Thirteen colorectal cancer patients participated in this study. Primary tumor tissues and matched normal blood tissues were collected for WGS in the mutation capture step, while plasma samples for cfDNA sequencing in the mutation recapture steps were obtained just prior to colorectal cancer surgery and 1-month post-surgery follow-up. Tumor DNA and germline DNA were analyzed using CancerVision, a CLIA-certified clinical-grade cancer WGS platform, in the mutation capture step. In the mutation recapture steps, somatically acquired mutations from the previous step were tracked in cfDNA samples using the Concatenating Original Duplex for Error Correction (CODEC) technique, a duplex DNA sequencing technique that examines both Watson and Crick strands of double-stranded DNA molecules to discern true mutations from sequencing noise. Results: The median WGS depth of tumor and germline tissues was 40x and 20x, respectively. The mean depth of cfDNA WGS with CODEC was 25x, with a median duplex sequencing rate of 70%. Overall, 4,828-301,434 somatic base substitutions (SBSs) per sample were discovered in the capture step. Four of the thirteen tumors exhibited hypermutator characteristics with microsatellite instability features. The CODEC technique demonstrated excellent capability in tracing cancer-specific mutations in cfDNA sequencing with a technical sequencing error rate of 4 x 10-7, defining the maximum technical LoD, which is 250-fold lower errors than conventional sequencing. In our sample cohort, tumor fractions in cfDNA sequencing were robustly estimated from 0.001% (10-5), below the LoD of conventional MRD methods. Conclusions: Our integration of tumor-WGS-informed duplex cfDNA sequencing methods significantly enhances the sensitivity of sequencing-based MRD assays, achieving a technical LoD limit of 10-7 for detecting ctDNA in cancer patients. These approaches represent a breakthrough in monitoring MRD in real-world cancer patients.

The numerical technique for simulation of viscous non-linear interactions between a solitary wave and a non-regular bottom was developed. It couples the boundary integral method used to determine the free surface deformations and the vortex scheme for integrating the fluid dynamic equations. To verify the model, a series of test calculations was carried out, where the obtained results were compared with our own experimental data and results known from similar studies by other authors. A good coincidence of the free surface elevation, as well as the velocity fields during the passage of a solitary wave over a thin submerged plate, was obtained. Systematic calculations of the interaction of a solitary wave with a submerged step in a wide range of wave amplitudes and step heights were performed. It is shown that when a wave emerges from deep water into the shallows, its evolution is determined by energy losses due to reflection, dispersion effects, and the generation of a vortex field. The dynamics of the wave on the submerged step depends on the coefficient of interaction, which is the ratio of the wave amplitude to the water depth above the step. Four types of wave behavior are possible above the step. Those are the weak interaction, when the wave gently splits into transmitted and reflected solitons; fission with development of two solitons behind the irregularity; fission with the generation of a dispersion chain of waves in the shallow water; and the collapse of a wave. The obtained critical value of the coefficient of interaction, at which the solitary wave is always breaking, is about 0.8, which is in congruence with the experimental data. Studies of patterns of vorticity generated by a solitary wave at the edge of a submerged step revealed two oppositely directed vortices with a horizontal axis, the scale of which is proportional to the water depth in a shallow channel. Their dynamics causes intensive exchange processes between deep water and shallows, as well as water flows from the bottom to the top and water mixing. The obtained data make it possible to predict in advance the development of processes and dangers caused by long nonlinear waves reaching the shelf.

Laser interferometry is a consolidated technique for materials structuring, enabling single step and large area patterning. Here we report the investigation of the morphological modification encoded on a thin film of a photosensitive material by the light interference pattern obtained from a laser operating in multiline mode. Four lines with equal intensity are retained, with the same p linear polarization. An azopolymer is exploited as medium for the holographic recording. Optical microscopy and profilometer measurements analyze the modification induced in the bulk and on the surface of the irradiated area. We show that the intensity profile of the interference patterns of two laser beams is the one obtained assuming each line of the laser as an independent oscillator of given intensity and wavelength, and how these light structures are faithfully replicated in the material bulk and on the topography of the free surface. Patterns at different length scales are achievable in a single step, that can be traced back to both interference fringes and wave envelopes. The proposed multi-wavelength holographic patterning provides a simple tool to generate complex light structures, able to perform multiscale modifications of photoresponsive materials

Coherent X-ray diffraction imaging is a promising technique for visualizing the structures of non-crystalline particles with dimensions of micrometers to sub-micrometers. Recently, X-ray free-electron laser sources have enabled efficient experiments in the `diffraction before destruction' scheme. Diffraction experiments have been conducted at SPring-8 Angstrom Compact free-electron LAser (SACLA) using the custom-made diffraction apparatus KOTOBUKI-1 and two multiport CCD detectors. In the experiments, ten thousands of single-shot diffraction patterns can be collected within several hours. Then, diffraction patterns with significant levels of intensity suitable for structural analysis must be found, direct-beam positions in diffraction patterns determined, diffraction patterns from the two CCD detectors merged, and phase-retrieval calculations for structural analyses performed. A software suite namedSITENNOhas been developed to semi-automatically apply the four-step processing to a huge number of diffraction data. Here, details of the algorithm used in the suite are described and the performance for approximately 9000 diffraction patterns collected from cuboid-shaped copper oxide particles reported. Using theSITENNOsuite, it is possible to conduct experiments with data processing immediately after the data collection, and to characterize the size distribution and internal structures of the non-crystalline particles.

The charge-membrane voltage ( Q-V) distribution of wild-type rabbit Na+/glucose transporter (rSGLT1) expressed in Xenopus oocytes was investigated in the absence of glucose, using the two-electrode voltage-clamp technique. Although this distribution is generally believed to be well represented by a two-state Boltzmann equation, we recently provided evidence for the existence of at least four states (Krofchick D and Silverman M. Biophys J 84: 3690–3702, 2003), confirming an earlier finding for human SGLT1 (Chen XZ, Coady MJ, and Lapointe JY. Biophys J 71: 2544–2552, 1996). We now extend our study of rSGLT1 pre-steady-state currents, employing high-resolution measurement and analysis of the Q-V distribution. A ramp, instead of a step, voltage change was used to prevent saturation of the apparatus in the first ∼1 ms. Transient currents were integrated out to 150 ms, instead of the standard 50–100 ms. Measurements were taken every 10 mV instead of the standard 20 mV. The Q-V distribution was fit with a two-, three-, and four-state Boltzmann equation and was described best by the three-state equation. The three-state fit produced two valences of 0.45 and 1.1 at two V0.5 values of −48 and −7.7, respectively. Our findings are critically compared with other published studies and the differences are discussed. An implication of the three-state fit is that the turnover rate of rSGLT1 is 34 s−1, i.e., 54% greater than previously reported (22 s−1). Our new findings support the concept that the sugar-free model of SGLT1 is more complex than generally accepted, most likely involving a minimum of four transition states.

A piezoelectric vibration energy harvester aiming at collecting energy from the operation of an electromagnetic digital actuator is presented. It is based on the frequency up-conversion and can simultaneously obtain the information of discrete position location. The objective is an improved reliability of such digital actuators ensuring sample controls of the actuator positions. The considered electromagnetic digital actuator is capable of achieving two-dimensional in-plane movements by switching a mobile permanent magnet among four discrete positions. The demonstration of a first step toward integrated additional autonomous functions scavenging a part of the mechanical energy of the mobile permanent magnet is achieved. The vibration energy harvester consists of a piezoelectric cantilever beam magnetically attached to the mobile permanent magnet. The limited magnetic interaction force allows a frequency up-conversion strategy to be set. The frequency up-conversion technique that is used here consists of a “low frequency” excitation that drives a much higher natural frequency oscillator. Indeed, once the energy harvester separates from the mobile permanent magnet, a free oscillation occurs and the induced mechanical energy is harvested. This design concept is numerically analyzed and experimentally validated. Harvested energy of 4.7 µJ is obtained from preliminary experiments using a simple out-of-plane cantilever beam with 9 N/m stiffness and 16 mN magnetic attraction between the vibration energy harvester and the mobile permanent magnet when they contact each other. This energy is in accordance with the requirements for wireless communication of simple information. Finally, an L-shaped cantilever beam optimized design is proposed for future in-plane integration.

AbstractThe effects of spanwise rotation on the channel flow across a symmetric sudden expansion are investigated using direct numerical simulation. Four rotation regimes are considered with the same Reynolds number$\mathit{Re}=5000$and expansion ratio$\mathit{Er}=3/2$. Upstream from the expansion, inflow turbulent conditions are generated realistically for each rotation rate through a very simple and efficient technique of recycling without the need for any precursor calculation. As the rotation is increased, the flow becomes progressively asymmetric with stabilization (destabilization) effects on the cyclonic (anticyclonic) side, respectively. These rotation effects, already present in the upstream channel, lead further downstream to an increase (reduction) of the separation size behind the cyclonic (anticyclonic) step. In the cyclonic separation, the free-shear layer created behind the step corner leads to the formation of large-scale spanwise vortices that become increasingly two-dimensional as the rotation is increased. Conversely, in the anticyclonic region, the turbulent structures in the separated layer are more elongated in the streamwise direction and also more active in promoting reattachment. For the highest rotation rate, a secondary separation is observed further downstream in the anticyclonic region, leading to the establishment of an elongated recirculation bubble that deflects the main flow towards the cyclonic wall. The highest level of turbulent kinetic energy is obtained at high rotation near the cyclonic reattachment in a region where stabilization effects are expected. The phenomenological model of absolute vortex stretching is found to be useful in understanding how the rotation influences the dynamics in the various regions of the flow.

Calcium-selective microelectrodes were used to measure the free calcium-ion concentration ([Ca2+]i) in early-cleaving embryonic cells of the golden medaka, Oryzias latipes, a fresh water teleost fish. Embryos could be dechorionated as early as the four-cell stage using a three-step technique consisting of removal of some yolk to enlarge the perivitelline space, partial digestion of the chorion with pancreatin, and removal of the weakened chorion with forceps. Dechorionated embryos underwent cleavage at a normal rate. Intracellular cytosolic [Ca2+]i was monitored by impaling blastomeres first with a microelectrode filled with 5 M potassium acetate to measure membrane potential, and a few minutes later with a calcium-selective microelectrode. During nine rounds of cytokinesis from a total of six different embryos, cytosolic [Ca2+]i remained constant (with apparently random fluctuations of less than +/- 0.1 microM). During two successive cleavages in one embryo, however, [Ca2+]i rose transiently fourfold above the original resting level to 1.32 and 1.20 microM in synchrony with each period of cytokinesis and returned after each rise to submicromolar levels. Because a calcium-selective microelectrode can detect [Ca2+]i changes only in the immediate vicinity of its 2-microns tip, we interpreted these data to suggest that, although [Ca2+]i in most areas of the cytosol remains between 0.01 and 0.40 microM (mean of 0.14 microM), there may be small regions of the cell in which [Ca2+]i undergoes a substantial increase at the time of cleavage. Evidence also is presented to suggest that the membrane potential in these blastomeres undergoes a slow net hyperpolarization during early cleavage stages.

Activation is a crucial step in mammalian somatic cell nuclear transfer (SCNT). Recently we described the application of the handmade cloning technique for porcine SCNT that uses oocytes without zonaa pellucidae (zona-free) in a micromanipulation-independent procedure (Kragh et al. 2004 Reprod. Fertil. Dev. 16, 315–18). The purpose of the present study was to investigate the effect of a combined electrical and chemical activation of zona-free porcine oocytes. Cumulus-oocyte complexes were aspirated from ovaries of sows and matured for 41 h. Subsequently, the cumulus cells were removed by the addition of 1 mg/mL hyaluronidase in HEPES-buffered TCM-199. For zonae pellucidae removal, oocytes were incubated in 8 mg/mL pronase in HEPES-buffered TCM-199 supplemented with 20% cattle serum for 10 s. Three independent experiments with four treatments were conducted, and oocytes were activated by a combined electrical and chemical activation. Oocytes were washed once in activation medium (0.3 M mannitol, 0.1 mM MgSO4, 0.1 mM CaCl2, and 0.01% polyvinyl alcohol) and transferred to a chamber with two wires (0.5-mm separation) covered with activation medium. After the electrical pulse, oocytes were incubated in culture medium (NCSU-37 containing 4 mg/mL BSA) supplemented with 5 μg/mL cytochalasin B and 10 μg/mL cycloheximide for 6 h. Activated oocytes were cultured in culture medium using the wells of wells system (Vajta et al. 2000 Mol. Reprod. Dev. 55, 256–64) in the submarine incubation system (Vajta et al. 1997 Theriogenology 48, 1379–85). The rate of development into blastocysts was checked on Day 7 of culture. In treatment 1, zona pellucida-intact oocytes were first activated by a single DC pulse of 1.25 kV/cm for 80 μs, and subsequently cultured in cytochalasin B and cycloheximide for 6 h. In treatments 2 and 3, oocytes without zonae pellucidae were activated by a single DC pulse of 1.25 and 0.85 kV/cm for 80 μs, respectively, and subsequently cultured in cytochalasin B and cycloheximide for 6 h. In treatment 4, oocytes without zonae pellucidae were bisected by hand under a stereomicroscope using a microblade in 5 μg/mL cytochalasin B in TCM-199 supplemented with 15 mg/mL BSA, re-fused/activated by a single DC pulse of 1.25 kV/cm for 80 μs in activation medium, and cultured in cytochalasin B and cycloheximide for 6 h. The rates of blastocyst formation from activated oocytes (mean ± SEM) in treatments 1, 2, 3, and 4 were 55 ± 4%, 40 ± 2%, 49 ± 1%, and 41 ± 8%, respectively. In conclusion, the combined electrical and chemical activation efficiently induced parthenogenetic development of zona-free oocytes. Also, a more authentic control model for activation during SCNT was established by activating and producing blasctocysts from re-fused bisected oocytes.

1. The horizontal and vertical vestibuloocular reflex (HVOR and VVOR, respectively) was studied in four chronically instrumented pigeons. Eye movements were measured using the magnetic search-coil technique and were produced by rotation in the dark. During the rotation paradigms, the pigeons were either pharmacologically aroused (using amphetamine) or drug free (normal). The pigeon HVOR and VVOR were tested using step and sinusoidal rotational stimulation. The range of frequencies (0.03-6.0 Hz) and the magnitude of the sinusoidal stimuli were chosen to match those used in a previous study of the responses of semicircular canal primary afferents (SCPAs) in unanesthetized (i.e., normal) pigeons. 2. The gain of the HVOR and VVOR in both normal and aroused pigeons was independent of stimulus magnitude (6-30 degrees/s) over the frequency range tested. In aroused pigeons, the frequency independent gain (G) of the HVOR (G = 0.6) and VVOR (G = 0.9) was roughly twice that for normal pigeons. Pigeon VOR phase under all combinations of orientation and arousal level was independent of stimulus magnitude except at the lowest frequency tested (0.03 Hz). At this frequency, phase lead decreased as stimulus magnitude increased for the HVOR and VVOR in both normal and aroused pigeons. 3. The step and sinusoidal gains were greater for the VVOR than for the HVOR under the same level of arousal. Neither the gain nor the dominant time constant of the VOR (tau vor) differed for rotation direction (clockwise or counterclockwise) for the HVOR or VVOR in normal or aroused pigeons. 4. The mean value of tau vor was 4.0 +/- 0.5 (SE) s as estimated from frequency response data and 4.3 +/- 0.4 s as estimated from step response data for the HVOR and VVOR in both normal and aroused pigeons. In comparison, the mean value of the dominant or cupular time constant (tau c) of normal pigeon SCPAs was approximately 10 s as estimated from frequency response data. These results indicate that tau vor is shorter than tau c in the pigeon. 5. At higher frequencies, the pigeon HVOR and VVOR exhibit an increasing phase lag unaccompanied by a gain change--characteristics produced by a pure time delay. The value of this time delay was about 7 ms for both the HVOR and VVOR in both normal and aroused pigeons. The HVOR and VVOR in normal and aroused pigeons lacked the higher frequency lead characteristics present in the frequency responses of most pigeon SCPAs.

A prototype convection-allowing system using the Advanced Research version of the Weather Research and Forecasting (WRF-ARW) Model and employing an ensemble Kalman filter (EnKF) data assimilation technique has been developed and used during the spring 2016 and 2017 Hazardous Weather Testbeds. This system assimilates WSR-88D reflectivity and radial velocity, geostationary satellite cloud water path (CWP) retrievals, and available surface observations over a regional domain with a 3-km horizontal resolution at 15-min intervals, with 3-km initial conditions provided by an experimental High-Resolution Rapid Refresh ensemble (HRRR-e). However, no information on upper-level thermodynamic conditions in cloud-free regions is currently assimilated, as few timely observations exist. One potential solution is to also assimilate clear-sky satellite radiances, which provide information on mid- and upper-tropospheric temperature and moisture conditions. This research assimilates GOES-13 imager water vapor band (6.5 μm) radiances using the GSI-EnKF system to take advantage of the Community Radiative Transfer Model (CRTM) integration. Results using four cases from May 2016 showed that assimilating radiances generally had a neutral-to-positive impact on the model analysis, reducing humidity bias and/or errors at the appropriate model levels where verification observations were present. The effects on high-impact weather forecasts, as verified against forecast reflectivity and updraft helicity, were mixed. Three cases (9, 22, and 24 May) showed some improvement in skill, while the other (25 May) performed worse, despite the improved environment. This research represents the first step in designing a high-resolution ensemble data assimilation system to use GOES-16 Advanced Baseline Imager data, which provides additional water vapor bands and increased spatial and temporal resolution.

Abstract In this paper, we investigate endovascular delivery to get a step ahead of the pharmacological limitations it has due to the complexity of dealing with a patient-specific vessel through a mathematical model. We divide the domain of computation into four sub-domains: the lumen, the lumen-tissue interface, the upper tissue and the lower tissue which are extracted from an asymmetric atherosclerotic image derived by the intravascular ultrasound (IVUS) technique. The injected drug at the luminal inlet is transported with the streaming blood which is considered Newtonian. An irreversible uptake kinetics of the injected drug at the lumen-tissue interface from the luminal side to the tissue domains is assumed. Subsequently, the drug is dispersed within the tissue followed by its retention in the extracellular matrix (ECM) and by receptor-mediated binding. The Marker and Cell (MAC) method has been leveraged to get a quantitative insight into the model considered. The effect of the wall absorption parameter on the concentration of all drug forms (free as well as two-phase bound) has been thoroughly investigated, and some other important factors, such as the averaged concentration, the tissue content, the fractional effect, the concentration variance and the effectiveness of drug have been graphically analyzed to gain a clear understanding of endovascular delivery. The simulated results predict that with increasing values of the absorption parameter, the averaged concentrations of all drug forms do decrease. An early saturation of binding sites takes place for smaller values of the absorption parameter, and also rapid saturation of ECM binding sites occurs as compared to receptor binding sites. Results also predict the influence of surface roughness as well as asymmetry of the domain about the centerline on the distribution and retention of drug. A thorough sensitivity analysis has been carried out to determine the influence of some parameters involved.

ABSTRAK Penelitian ini bertujuan untuk mengetahui dan mendeskripsikan bentuk organisasi Mahasiswa Masjid di Masjid Ulul Azmi Universitas Airlangga Surabaya. Karena organisasi ini memiliki pengelolaan yang berbeda dengan organisasi lain dalam hal kegiatan memakmurkan masjid. Penelitian ini menggunakan metode kualitatif dengan pendekatan studi kasus. Untuk pengumpulan data menggunakan teknik wawancara, observasi, dan dokumentasi. Data yang didapat diuji kevalidan datanya menggunakan triangulasi. Selanjutnya peneliti melakukan analisis dengan teori Bentuk Organisasi dalam buku Manajemen Organisasi oleh Muhammad Rifa’I dan Muhammad Fadhli. Dari analisis tersebut menghasilkan temuan yaitu diantara keempat bentuk organisasi (Lini, Fungsional, Fungsional dan Lini, serta Lini dan Staf) menunjukkan bahwa ternyata bentuk Organisasi Mahasiswa Masjid adalah Organisasi Lini. Karena organisasi ini lebih memenuhi ciri - ciri Organisasi Lini daripada yang lainnya. Sehingga Peneliti menyampaikan bahwa Organisasi Mahasiswa Masjid lebih efektif dalam hal keorganisasian dan cukup baik menerapkan bentuk organisasi Lini dalam hal memakmurkan masjid Ulul Azmi Universitas Airlangga Surabaya. Kata kunci : Bentuk Organisasi, Mahasiswa Masjid, Masjid Ulul Azmi ABSTRACT The objective of this research is to find out and describe the structure of Mosque Student Organization (Mahasiswa Masjid) at Airlangga University Mosque (Ulul Azmi) Surabaya. Since this organization owns different management from other organizations in terms of prospering mosque activities. This research applies qualitative method with case study approach, while for data collection uses interview technique, free-guided observation and documentation. The data obtained are tested by using triangulation technique. The next step is the researcher conducted analysis based on theories organization structure in the book entitled "Manajemen Organisasi" written by Muhammad Rifa’i and Muhammad Fadhli. From the analysis result, it is concluded that among the four forms of organization (Line, Functional, Functional and Line, Staffing), Mosque Student Organization (Mahasiswa Masjid) is classified as Line Organization since the organization has fulfilled the characteristics of Line Organization rather than the others. Eventually the researcher draws conclusion that Mosque Student Organization (Mahasiswa Masjid) is more effective in terms of organization and it is quite proper and good in implementing Line Organization form in terms of prospering Airlangga University Mosque (Ulul Azmi) Surabaya. Keyword: Mosque Student Organization (Mahasiswa Masjid), Organization Structures, Airlangga University Mosque (Ulul Azmi).

Background: There are several methods for the quantification of biomass in SSF, such as glucosamine measurement, ergosterol content, protein concentration, change in dry weight or evolution of CO2 production. However, all have drawbacks when obtaining accurate data on the progress of the SSF due to the dispersion in cell growth on the solid substrate, and the difficulty encountered in separating the biomass. Studying the disadvantages associated with the process of biomass quantification in SSF, the monitoring of the growth of biomass by a technique known as digital image processing (DIP), consists of obtaining information on the production of different compounds during fermentation, using colorimetric methods based on the pixels that are obtained from photographs. Objective: The purpose of this study was to know about the state of the technology and the advantages of DIP. Methods: The methodology employed four phases; the first describes the search equations for the SSF and the DIP. A search for patents related to SSF and DIP carried out in the Free Patents Online and Patent inspiration databases. Then there is the selection of the most relevant articles in each of the technologies. As a third step, modifications for obtaining the best adjustments were also carried out. Finally, the analysis of the results was done and the inflection years were determined by means of six mathematical models widely studied. Results: For these models, the inflection years were 2018 and 2019 for both the SSF and the DIP. Additionally, the main methods for the measurement of biomass in SSF were found, and are also indicated in the review, as DIP measurement processes have already been carried out using the same technology. Conclusion: In addition, the DIP has shown satisfactory results and could be an interesting alternative for biomass measurement in SSF, due to its ease and versatility.

This study aimed to assess the psychological effects experienced by patients admitted to the intensive care unit (ICU). Following ethical approval, the study was conducted as a cross-sectional survey at Bahria International Hospital ICU between January 2022 and December 2022. The inclusion criteria required patients to be over 18 years of age, have stayed in the ICU for at least 24 hours, be aware during the assessment, and provide informed consent for research participation. Patients who failed to complete the assessment or were transferred out of the ICU were excluded from the study. The data was analyzed using a non-probability sampling technique and the SPSS-24 version. A chi-square value of less than 0.5 was considered significant. The data from a total of 161 patients was evaluated. Of these, 72 patients (44%) were diagnosed with depression, while 89 patients (55.2%) had medical cases. Males outnumbered females, with 94 (58%) male patients and 67 (42%) female patients. 26 patients (17%) had a hospital stay of over 2 weeks, compared to 135 (83%) who were discharged within 2 weeks. One hundred fifty-one patients (93%) did not show signs of anxiety, while 10 (6%) tested positive. Nine patients tested positive for amnesia, while 152 did not. One hundred fifty-five patients (96%) reported no hallucinations, while 6 patients (4%) believed they had experienced hallucinations. Seventy-four patients (46%) tested negative for post-traumatic stress disorder (PTSD), while 87 patients (54%) claimed to experience PTSD. Of the ICU admissions, 89 (55%) were due to medical cases, while 27 (16.7%) were surgical. The study highlights the need for implementing a bedside screening instrument and physician approval to improve the identification and early detection of psychological effects in critically ill ICU patients. The first step towards preventing and developing a future ICU free from psychological effects is identifying the incidence and risk factors associated with such impacts. The complex psychosocial impacts experienced by critically ill ICU patients require more attention and research.

The Internet of Vehicles (IoV) is witnessed to play the leading role in the future of Intelligent Transportation Systems (ITS). Though many works have focused on IoV improvement, there is still a lack of performance due to insufficient spectrum availability, lower data rates, and the involvement of attackers. This paper considers all three issues by developing a novel mmWave-assisted Cognitive Radio based IoV (CR-IoV) model. The integration of CR in IoV resolves the issue of spectrum management, while mmWave technology ensures symmetry in acquiring higher data rates for Secondary Users (SUs). With the proposed mmWave-assisted CR-IoV model, symmetric improvements in network performance were achieved in three main areas: security, beamforming, and routing. Optimum detection mechanisms isolate malicious Secondary Users (SUs) in the overall network. First, Spectrum Sensing Data Falsification (SSDF) attack is detected by a Hybrid Kernel-based Support Vector Machine (HK-SVM), which is the lightweight Machine Learning (ML) technique. Then, the Primary User Emulation (PUE) attack is detected by a hybrid approach, namely the Fang Algorithm-based Time Difference of Arrival (FA-TDoA) method. Further, security is assured by validating the legitimacy of each SU through a Lightweight ID-based Certificate Validation mechanism. To accomplish this, we employed the Four Q-curve asymmetric cryptographic algorithm. Overall, the proposed dual-step security provisioning approach assures that the network is free from attackers. Next, beamforming is performed for legitimate SUs by a 3D-Beamforming algorithm that relies on Array Factor (AF) and Beampattern Function. Finally, routing is enabled by formulating Forwarding Zone (FZ) based on the forwarding angle. In the forwarding zone, optimal forwarders are selected by the Multi-Objective Whale Optimization (MOWO) algorithm. Here, a new potential score is formulated for fitness evaluation. Finally, the proposed mmWave-assisted CR-IoV model is validated through extensive simulations in the ns-3.26 simulation tool. The evaluation shows better performance in terms of throughput, packet delivery ratio, delay, bit error rate, and detection accuracy.

The objective of the research was to determine the occurrence of microorganisms of the Salmonella spp. and Listeria spp. in raw and frozen (cooked) snail meat obtained from both free-living and farmed edible snails. The research material comprised meat samples collected from three snail species (25g from each), that is, Roman snail (Helix pomatia – HP), small brown garden snail (Cornu aspersum aspersum – CAA) and large brown garden snail (Cornu aspersum maxima – CAM). Roman snails came from their natural environment and were harvested in Wielkopolska Voivodeship and Lower Silesia Voivodeship (regions A and B, respectively). The Cornu genus snails were obtained from two heliciculture farms located in the abovementioned voivodeships (farms A and B, respectively). On both farms, the snails were maintained under the mixed rearing system. The raw meat samples taken from the edible portion of snails, that is, the foot with collar and a fragment of the mantle, were obtained after the snails were sacrificed in the laboratory. The frozen meat samples, on the other hand, came from a snail meat processing facility. A total of 300 samples were examined for the presence of Salmonella spp., and 240 for the presence of Listeria spp. The research also included pooled soil samples of 0.5 kg each collected from polytunnels (in the pre-fattening stage) and outdoor farming plots (in the fattening stage). The tests for the Salmonella presence were performed in accordance with Polish standard PN-EN ISO 6579:2003, and the test for Listeria complied with PN-EN ISO 11290-1:1999. Listeria monocytogenes was identified by the PCR technique. Salmonella spp. were not detected in any of the 300 samples of raw and cooked snail meat under study. Nor were these pathogens isolated from the soil samples. The absence of these bacteria in the raw meat samples indicates that Salmonella spp. did not occur in either the natural habitat of Roman snails or the two farms producing Cornu genus snails. On the other hand, bacteria of Listeria spp. were detected in 101 (42.1%) snail meat samples. A particularly high load of microbiota was found in raw meat, as these bacteria contaminated from 60% (for HP from region A and CAM from farm B) up to 75% (for CAA from farm A) of samples. Notably, a markedly lower percentage (35%) of samples containing Listeria spp. was found only among the Roman snail raw meat samples from the region B. Listeria spp. were also detected in all the soil samples. Thermal treatment of meat achieved a substantial reduction in the load of Listeria spp., but did not eliminate it. The frequency of this genus in frozen meat samples was from 63.5% (for CAM from farm A) to 15.4% (for CAA from farm B) of that in raw meat. The PCR technique was used identify 15 selected strains, including 11 from raw meat samples and 4 from cooked meat. A total of 5 isolates were recognized as Listeria monocytogenes (2.1% of all samples examined and 4.95% of samples with Listeria spp.). All of them originated from the raw meat of farmed snails, including one (CAA) from the farm A and four (3 CAA and 1 CAM) from the farm B. Bacteria of the Salmonella and Listeria genera occur in the natural habitat of edible snails, which poses a potential hazard to human health. Effective implementation of control programmes at the primary production stage is the first step that could considerably limit the presence of these pathogens in farmed snails and, consequently, in snail meat. .

Background Molecular characterization of B-cell non-Hodgkin lymphoma (B-NHL), through circulating tumor DNA (ctDNA) assessment of minimal residual disease (MRD) has been proposed as a tool to predict clinical outcome. Odronextamab, a CD20×CD3 bispecific antibody, demonstrated deep and durable responses and a generally manageable safety profile in patients (pts) with R/R FL or DLBCL in the Phase 2 ELM-2 study (NCT03888105; Kim TM et al. and Kim WS et al. ASH. 2022). In the overall populations, 12-month PFS rates were 64% and 29%, respectively. Using ctDNA from ELM-2, we show that these assessments associate with clinical outcomes following odronextamab treatment. Methods In ELM-2, pts received IV odronextamab in 21-day cycles, with step-up dosing in Cycle (C) 1, 80 mg (FL)/160 mg (DLBCL) QW in C2-4, then 160 mg (FL)/320 mg (DLBCL) Q2W until disease progression or unacceptable toxicity. Baseline (BL) ctDNA and tumor biopsies were used for molecular profiling. BL and on-treatment ctDNA were used for MRD determination in the biomarker population (BP; pts required ≥1 available plasma biomarker sample to be included in the BP). The first post-BL ctDNA sample was collected on C5 Day (D) 1, at the time of positron emission tomography-computed tomography (PET-CT). A modified AVENIO ctDNA analysis workflow (Roche; research only) was used for next-generation sequencing, based on the cancer personalized profiling by deep sequencing technique (Kurtz et al. J Clin Oncol. 2018). Whole blood cell pellets were used to filter out germline allele variants. MRD negativity was reported when the P value for variant allele frequency was >0.005. Results The BP comprised 53 FL pts and 63 DLBCL pts; at BL, all FL pts and all but one DLBCL pt were MRD(+). Pts remaining on study until C5D1 had similar PFS regardless of whether they were in the BP or overall population (FL, n=111; DLBCL, n=83). Pts who were MRD(-) at C5D1 had significantly longer PFS vs. those who remained MRD(+) (FL: HR 0.27 [95% CI 0.09-0.84], P=0.024 [Fig. 1a]; DLBCL: HR 0.29 [95% CI 0.12-0.71], P=0.007). In pts with FL achieving complete response (CR) by PET-CT at C5D1, a trend for prolonged PFS was observed in those who were MRD(-) (n=26) at this timepoint vs. those who were MRD(+) (n=17; HR 0.29 [95% CI 0.07-1.1], P=0.072). Pts with DLBCL who were MRD(-) at C5D1 (n=20) had similar PFS benefit regardless of PET-CT CR status (HR 0.56 [95% CI 0.10-3.11], P=0.511). Four DLBCL pts who were MRD(-) and did not achieve CR by PET-CT at C5D1 (partial response, n=3; stable disease, n=1) went on to achieve PET-CT CR at a later timepoint. Mutational analyses of BL ctDNA identified TP53 as the most frequent mutation (FL, n=34/53 [64%] mutation-evaluable pts; DLBCL, n=44/58 [76%]). In FL pts, TP53 mutations were associated with MRD(+) status at C5D1 (Fisher's exact test, P=0.002) and predicted significantly shorter PFS (HR 3.57 [95% CI 1.01-12.69]; P=0.049); this association was not observed in DLBCL. LymphGen classification (Wright et al. Cancer Cell. 2020) of BL ctDNA in pts with DLBCL identified mostly MCD and EZB subtypes (MCD, n=15; EZB, n=14; ST2, n=1; BN2, n=1; other, n=26). EZB-subtype pts treated with odronextamab had significantly longer PFS compared with MCD-subtype pts (HR 0.23 [95% CI 0.07-0.83]; P=0.025 [Fig. 1b]). Using BL ctDNA, cell of origin was determined in 43/58 pts with DLBCL; odronextamab treatment led to similar PFS in higher-risk non-germinal-center B-cell-like (non-GCB, n=18 [42%]) pts vs. GCB pts (n=25 [58%]; HR 1.62 [95% CI 0.72-3.62]; P=0.244). Further molecular assessment focused on gene fusions in DLBCL pts in the BP (39 with local laboratory gene fusion and ctDNA analyses, 24 with only ctDNA analyses). Odronextamab led to similar PFS in pts with double-hit (n=15) or triple-hit (n=5) fusions compared to those without (n=43; P=0.343 and P=0.140, respectively). Conclusions This study is among the first to analyze ctDNA in pts with R/R FL and DLBCL in a pivotal trial. This non-invasive method allows molecular characterization of pts with no available tissue, enabling identification of high-risk subgroups. CtDNA MRD status at C5D1 of odronextamab treatment was highly associated with PFS in pts with FL and DLBCL and in the future could form the basis of response-directed treatment paradigms. Molecular characterization in tumor biopsies, including CD20, will be presented. Ongoing monitoring of ctDNA may serve as an important early progression marker in R/R FL and DLBCL.

This paper aims to portray the overall picture of poverty in the world and mentions the key solution to overcome poverty from a critical perspective. The data and figures were quoted from a number of researchers and organizations in the field of poverty around the world. Simultaneously, the information strengthens the correlations among poverty and lack of education. Only appropriate philosophies of education can improve the country’s socio-economic conditions and contribute to effective solutions to worldwide poverty. In the 21st century, despite the rapid development of science and technology with a series of inventions brought into the world to make life more comfortable, human poverty remains a global problem, especially in developing countries. Poverty, according to Lister (2004), is reflected by the state of “low living standards and/or inability to participate fully in society because of lack of material resources” (p.7). The impact and serious consequences of poverty on multiple aspects of human life have been realized by different organizations and researchers from different contexts (Fraser, 2000; Lister, 2004; Lipman, 2004; Lister, 2008). This paper will indicate some of the concepts and research results on poverty. Figures and causes of poverty, and some solutions from education as a key breaker to poverty will also be discussed. Creating a universal definition of poverty is not simple (Nyasulu, 2010). There are conflicts among different groups of people defining poverty, based on different views and fields. Some writers, according to Nyasulu, tend to connect poverty with social problems, while others focus on political or other causes. However, the reality of poverty needs to be considered from different sides and ways; for that reason, the diversity of definitions assigned to poverty can help form the basis on which interventions are drawn (Ife and Tesoriero, 2006). For instance, in dealing with poverty issues, it is essential to intervene politically; economic intervention is very necessary to any definition of this matter. A political definition necessitates political interventions in dealing with poverty, and economic definitions inevitably lead to economic interventions. Similarly, Księżopolski (1999) uses several models to show the perspectives on poverty as marginal, motivation and socialist. These models look at poverty and solutions from different angles. Socialists, for example, emphasize the responsibilities of social organization. The state manages the micro levels and distributes the shares of national gross resources, at the same time fighting to maintain the narrow gap among classes. In his book, Księżopolski (1999) also emphasizes the changes and new values of charity funds or financial aid from churches or organizations recognized by the Poor Law. Speaking specifically, in the new stages poverty has been recognized differently, and support is also delivered in limited categories related to more specific and visible objectives, with the aim of helping the poor change their own status for sustainable improvement. Three ways of categorizing the poor and locating them in the appropriate places are (1) the powerless, (2) who is willing to work and (3) who is dodging work. Basically, poverty is determined not to belong to any specific cultures or politics; otherwise, it refers to the situation in which people’s earnings cannot support their minimum living standard (Rowntree, 1910). Human living standard is defined in Alfredsson & Eide’s work (1999) as follows: “Everyone has the right to a standard of living adequate for the health and well-being of himself and his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control.” (p. 524). In addition, poverty is measured by Global Hunger Index (GHI), which is calculated by the International Food Policy Institute (IFPRI) every year. The GHI measures hunger not only globally, but also by country and region. To have the figures multi-dimensionally, the GHI is based on three indicators: 1. Undernourishment: the proportion of the undernourished as a percentage of the population (reflecting the share of the population with insufficient calorie intake). 2. Child underweight: the proportion of children under age 5 who are underweight (low weight for their age, reflecting wasting, stunted growth or both), which is one indicator of child under-nutrition. 3. Child mortality: the mortality rate of children under 5 (partially reflecting the fatal synergy of inadequate dietary intake and unhealthy environments). Apart from the individual aspects and the above measurement based on nutrition, which help partly imagine poverty, poverty is more complicated, not just being closely related to human physical life but badly affecting spiritual life. According to Jones and Novak (1999 cited in Lister, 2008), poverty not only characterizes the precarious financial situation but also makes people self-deprecating. Poverty turns itself into the roots of shame, guilt, humiliation and resistance. It leads the poor to the end of the road, and they will never call for help except in the worst situations. Education can help people escape poverty or make it worse. In fact, inequality in education has stolen opportunity for fighting poverty from people in many places around the world, in both developed and developing countries (Lipman, 2004). Lipman confirms: “Students need an education that instills a sense of hope and possibility that they can make a difference in their own family, school, and community and in the broader national and global community while it prepare them for multiple life choices.” (p.181) Bradshaw (2005) synthesizes five main causes of poverty: (1) individual deficiencies, (2) cultural belief systems that support subcultures of poverty, (3) economic, political and social distortions or discrimination, (4) geographical disparities and (5) cumulative and cyclical interdependencies. The researcher suggests the most appropriate solution corresponding with each cause. This reflects the diverse causes of poverty; otherwise, poverty easily happens because of social and political issues. From the literature review, it can be said that poverty comes from complex causes and reasons, and is not a problem of any single individual or country. Poverty has brought about serious consequences and needs to be dealt with by many methods and collective effort of many countries and organizations. This paper will focus on representing some alarming figures on poverty, problems of poverty and then the education as a key breaker to poverty. According to a statistics in 2012 on poverty from the United Nations Development Program (UNDP), nearly half the world's population lives below the poverty line, of which is less than $1.25 a day . In a statistics in 2015, of every 1,000 children, 93 do not live to age 5 , and about 448 million babies are stillborn each year . Poverty in the world is happening alarmingly. According to a World Bank study, the risk of poverty continues to increase on a global scale and, of the 2009 slowdown in economic growth, which led to higher prices for fuel and food, further pushed 53 million people into poverty in addition to almost 155 million in 2008. From 1990 to 2009, the average GHI in the world decreased by nearly one-fifth. Many countries had success in solving the problem of child nutrition; however, the mortality rate of children under 5 and the proportion of undernourished people are still high. From 2011 to 2013, the number of hungry people in the world was estimated at 842 million, down 17 percent compared with the period 1990 to 1992, according to a report released by the Food and Agriculture Organization of the United Nations (FAO) titled “The State of Food Insecurity in the World 2013” . Although poverty in some African countries had been improved in this stage, sub-Saharan Africa still maintained an area with high the highest percentage of hungry people in the world. The consequences and big problems resulting from poverty are terrible in the extreme. The following will illustrate the overall picture under the issues of health, unemployment, education and society and politics ➢ Health issues: According a report by Manos Unidas, a non- government organization (NGO) in Spain , poverty kills more than 30,000 children under age 5 worldwide every day, and 11 million children die each year because of poverty. Currently, 42 million people are living with HIV, 39 million of them in developing countries. The Manos Unidas report also shows that 15 million children globally have been orphaned because of AIDS. Scientists predict that by 2020 a number of African countries will have lost a quarter of their population to this disease. Simultaneously, chronic drought and lack of clean water have not only hindered economic development but also caused disastrous consequences of serious diseases across Africa. In fact, only 58 percent of Africans have access to clean water; as a result, the average life expectancy in Africa is the lowest in the world, just 45 years old (Bui, 2010). ➢ Unemployment issues: According to the United Nations, the youth unemployment rate in Africa is the highest in the world: 25.6 percent in the Middle East and North Africa. Unemployment with growth rates of 10 percent a year is one of the key issues causing poverty in African and negatively affecting programs and development plans. Total African debt amounts to $425 billion (Bui, 2010). In addition, joblessness caused by the global economic downturn pushed more than 140 million people in Asia into extreme poverty in 2009, the International Labor Organization (ILO) warned in a report titled The Fallout in Asia, prepared for the High-Level Regional Forum on Responding to the Economic Crisis in Asia and the Pacific, in Manila from Feb. 18 to 20, 2009 . Surprisingly, this situation also happens in developed countries. About 12.5 million people in the United Kingdom (accounting for 20 percent of the population) are living below the poverty line, and in 2005, 35 million people in the United States could not live without charity. At present, 620 million people in Asia are living on less than $1 per day; half of them are in India and China, two countries whose economies are considered to be growing. ➢ Education issues: Going to school is one of the basic needs of human beings, but poor people cannot achieve it. Globally, 130 million children do not attend school, 55 percent of them girls, and 82 million children have lost their childhoods by marrying too soon (Bui, 2010). Similarly, two-thirds of the 759 million illiterate people in total are women. Specifically, the illiteracy rate in Africa keeps increasing, accounting for about 40 percent of the African population at age 15 and over 50 percent of women at age 25. The number of illiterate people in the six countries with the highest number of illiterate people in the world - China, India, Indonesia, Brazil, Bangladesh and Egypt - reached 510 million, accounting for 70 percent of total global illiteracy. ➢ Social and political issues: Poverty leads to a number of social problems and instability in political systems of countries around the world. Actually, 246 million children are underage labors, including 72 million under age 10. Simultaneously, according to an estimate by the United Nations (UN), about 100 million children worldwide are living on the streets. For years, Africa has suffered a chronic refugee problem, with more than 7 million refugees currently and over 200 million people without homes because of a series of internal conflicts and civil wars. Poverty threatens stability and development; it also directly influences human development. Solving the problems caused by poverty takes a lot of time and resources, but afterward they can focus on developing their societies. Poverty has become a global issue with political significance of particular importance. It is a potential cause of political and social instability, even leading to violence and war not only within a country, but also in the whole world. Poverty and injustice together have raised fierce conflicts in international relations; if these conflicts are not satisfactorily resolved by peaceful means, war will inevitably break out. Obviously, poverty plus lack of understanding lead to disastrous consequences such as population growth, depletion of water resources, energy scarcity, pollution, food shortages and serious diseases (especially HIV/AIDS), which are not easy to control; simultaneously, poverty plus injustice will cause international crimes such as terrorism, drug and human trafficking, and money laundering. Among recognizable four issues above which reflected the serious consequences of poverty, the third ones, education, if being prioritized in intervention over other issues in the fighting against poverty is believed to bring more effectiveness in resolving the problems from the roots. In fact, human being with the possibility of being educated resulted from their distinctive linguistic ability makes them differential from other beings species on the earth (Barrow and Woods 2006, p.22). With education, human can be aware and more critical with their situations, they are aimed with abilities to deal with social problems as well as adversity for a better life; however, inequality in education has stolen opportunity for fighting poverty from unprivileged people (Lipman, 2004). An appropriate education can help increase chances for human to deal with all of the issues related to poverty; simultaneously it can narrow the unexpected side-effect of making poverty worse. A number of philosophies from ancient Greek to contemporary era focus on the aspect of education with their own epistemology, for example, idealism of Plato encouraged students to be truth seekers and pragmatism of Dewey enhanced the individual needs of students (Gutex, 1997). Education, more later on, especially critical pedagogy focuses on developing people independently and critically which is essential for poor people to have ability of being aware of what they are facing and then to have equivalent solutions for their problems. In other words, critical pedagogy helps people emancipate themselves and from that they can contribute to transform the situations or society they live in. In this sense, in his most influential work titled “Pedagogy of the Oppressed” (1972), Paulo Freire carried out his critical pedagogy by building up a community network of peasants- the marginalized and unprivileged party in his context, aiming at awakening their awareness about who they are and their roles in society at that time. To do so, he involved the peasants into a problem-posing education which was different from the traditional model of banking education with the technique of dialogue. Dialogue wasn’t just simply for people to learn about each other; but it was for figuring out the same voice; more importantly, for cooperation to build a social network for changing society. The peasants in such an educational community would be relieved from stressfulness and the feeling of being outsiders when all of them could discuss and exchange ideas with each other about the issues from their “praxis”. Praxis which was derived from what people act and linked to some values in their social lives, was defined by Freire as “reflection and action upon the world in order to transform it” (p.50). Critical pedagogy dialogical approach in Pedagogy of the Oppressed of Freire seems to be one of the helpful ways for solving poverty for its close connection to the nature of equality. It doesn’t require any highly intellectual teachers who lead the process; instead, everything happens naturally and the answers are identified by the emancipation of the learners themselves. It can be said that the effectiveness of this pedagogy for people to escape poverty comes from its direct impact on human critical consciousness; from that, learners would be fully aware of their current situations and self- figure out the appropriate solutions for their own. In addition, equality which was one of the essences making learners in critical pedagogy intellectually emancipate was reflected via the work titled “The Ignorant Schoolmaster” by Jacques Rancière (1991). In this work, the teacher and students seemed to be equal in terms of the knowledge. The explicator- teacher Joseph Jacotot employed the interrogative approach which was discovered to be universal because “he taught what he didn’t know”. Obviously, this teacher taught French to Flemish students while he couldn’t speak his students’ language. The ignorance which was not used in the literal sense but a metaphor showed that learners can absolutely realize their capacity for self-emancipation without the traditional teaching of transmission of knowledge from teachers. Regarding this, Rancière (1991, p.17) stated “that every common person might conceive his human dignity, take the measure of his intellectual capacity, and decide how to use it”. This education is so meaningful for poor people by being able to evoking their courageousness to develop themselves when they always try to stay away from the community due the fact that poverty is the roots of shame, guilt, humiliation and resistance (Novak, 1999). The contribution of critical pedagogy to solving poverty by changing the consciousness of people from their immanence is summarized by Freire’s argument in his “Pedagogy of Indignation” as follows: “It is certain that men and women can change the world for the better, can make it less unjust, but they can do so from starting point of concrete reality they “come upon” in their generation. They cannot do it on the basis of reveries, false dreams, or pure illusion”. (p.31) To sum up, education could be an extremely helpful way of solving poverty regarding the possibilities from the applications of studies in critical pedagogy for educational and social issues. Therefore, among the world issues, poverty could be possibly resolved in accordance with the indigenous people’s understanding of their praxis, their actions, cognitive transformation, and the solutions with emancipation in terms of the following keynotes: First, because the poor are powerless, they usually fall into the states of self-deprecation, shame, guilt and humiliation, as previously mentioned. In other words, they usually build a barrier between themselves and society, or they resist changing their status. Therefore, approaching them is not a simple matter; it requires much time and the contributions of psychologists and sociologists in learning about their aspirations, as well as evoking and nurturing the will and capacities of individuals, then providing people with chances to carry out their own potential for overcoming obstacles in life. Second, poverty happens easily in remote areas not endowed with favorable conditions for development. People there haven’t had a lot of access to modern civilization; nor do they earn a lot of money for a better life. Low literacy, together with the lack of healthy forms of entertainment and despair about life without exit, easily lead people into drug addiction, gambling and alcoholism. In other words, the vicious circle of poverty and powerlessness usually leads the poor to a dead end. Above all, they are lonely and need to be listened to, shared with and led to escape from their states. Community meetings for exchanging ideas, communicating and immediate intervening, along with appropriate forms of entertainment, should be held frequently to meet the expectations of the poor, direct them to appropriate jobs and, step by step, change their favorite habits of entertainment. Last but not least, poor people should be encouraged to participate in social forums where they can both raise their voices about their situations and make valuable suggestions for dealing with their poverty. Children from poor families should be completely exempted from school fees to encourage them to go to school, and curriculum should also focus on raising community awareness of poverty issues through extracurricular and volunteer activities, such as meeting and talking with the community, helping poor people with odd jobs, or simply spending time listening to them. Not a matter of any individual country, poverty has become a major problem, a threat to the survival, stability and development of the world and humanity. Globalization has become a bridge linking countries; for that reason, instability in any country can directly and deeply affect the stability of others. The international community has been joining hands to solve poverty; many anti-poverty organizations, including FAO (Food and Agriculture Organization), BecA (the Biosciences eastern and central Africa), UN-REDD (the United Nations Programme on Reducing Emissions from Deforestation and Forest Degradation), BRAC (Building Resources Across Communities), UNDP (United Nations Development Programme), WHO (World Health Organization) and Manos Unidas, operate both regionally and internationally, making some achievements by reducing the number of hungry people, estimated 842 million in the period 1990 to 1992, by 17 percent in 2011- to 2013 . The diverse methods used to deal with poverty have invested billions of dollars in education, health and healing. The Millennium Development Goals set by UNDP put forward eight solutions for addressing issues related to poverty holistically: 1) Eradicate extreme poverty and hunger. 2) Achieve universal primary education. 3) Promote gender equality and empower women. 4) Reduce child mortality. 5) Improve maternal health. 6) Combat HIV/AIDS, malaria and other diseases. 7) Ensure environmental sustainability. 8) Develop a global partnership for development. Although all of the mentioned solutions carried out directly by countries and organizations not only focus on the roots of poverty but break its circle, it is recognized that the solutions do not emphasize the role of the poor themselves which a critical pedagogy does. More than anyone, the poor should have a sense of their poverty so that they can become responsible for their own fate and actively fight poverty instead of waiting for help. It is not different from the cores of critical theory in solving educational and political issues that the poor should be aware and conscious about their situation and reflected context. It is required a critical transformation from their own praxis which would allow them to go through a process of learning, sharing, solving problems, and leading to social movements. This is similar to the method of giving poor people fish hooks rather than giving them fish. The government and people of any country understand better than anyone else clearly the strengths and characteristics of their homelands. It follows that they can efficiently contribute to causing poverty, preventing the return of poverty, and solving consequences of the poverty in their countries by many ways, especially a critical pedagogy; and indirectly narrow the scale of poverty in the world. In a word, the wars against poverty take time, money, energy and human resources, and they are absolutely not simple to end. Again, the poor and the challenged should be educated to be fully aware of their situation to that they can overcome poverty themselves. They need to be respected and receive sharing from the community. All forms of discrimination should be condemned and excluded from human society. When whole communities join hands in solving this universal problem, the endless circle of poverty can be addressed definitely someday. More importantly, every country should be responsible for finding appropriate ways to overcome poverty before receiving supports from other countries as well as the poor self-conscious responsibilities about themselves before receiving supports from the others, but the methods leading them to emancipation for their own transformation and later the social change.

Abstract Background The Serial Transverse Enteroplasty Procedure (STEP) Registry has reported a 47% success to achieve enteral autonomy in pediatric short bowel syndrome (SBS). We have performed the STEP with a technical modification (MSTEP) consisting in stapler application without mesenteric defects that can also be applied to the duodenum. Our experience with this technique is described. Materials and Methods In this study, 16 children with SBS underwent MSTEP (2005–2019). Indications were nutritional autonomy achievement (n = 11, with duodenal lengthening in 5/11) and bacterial overgrowth treatment (n = 5). Results With a median follow-up of 5.8 years (0.7–13.7 years), 5 of 11 (45%) patients achieved enteral autonomy, 4 of them with duodenal lengthening. Four of four who preserved > 50% colon, while only one of seven with < 50% of colon achieved enteral autonomy (p < 0.05). After redo procedures, three of four attained enteral autonomy. Thus, 8 of 11 (73%) progressed to enteral autonomy, including all with duodenal lengthening. One child, already parenteral nutrition free, died due to central line sepsis. All the patients from the bacterial translocation group improved their metabolic/nutritional status, but one required subsequent enterectomy of the lengthened intestine due to multiple ulcers in the staple lines. Conclusion The effectiveness of MSTEP to achieve enteral autonomy seems similar to the classical STEP. It can be applied to the duodenum. The retained colon length may influence the post-STEP enteral autonomy achievement.

AbstractPurposeTo reduce the ringing artifacts of the motion‐resolved images in free‐breathing dynamic pulmonary MRI.MethodsA golden‐step based interleaving (GSI) technique was proposed to reduce ringing artifacts induced by diaphragm drifting. The pulmonary MRI data were acquired using a superior–inferior navigated 3D radial UTE sequence in an interleaved manner during free breathing. Successive interleaves were acquired in an incoherent fashion along the polar direction. Four‐dimensional images were reconstructed from the motion‐resolved k‐space data obtained by retrospectively binning. The reconstruction algorithms included standard nonuniform fast Fourier transform (NUFFT), Voronoi‐density‐compensated NUFFT, extra‐dimensional UTE, and motion‐state weighted motion‐compensation reconstruction. The proposed interleaving technique was compared with a conventional sequential interleaving (SeqI) technique on a phantom and eight subjects.ResultsThe quantified ringing artifacts level in the motion‐resolved image is positively correlated with the quantified nonuniformity level of the corresponding k‐space. The nonuniformity levels of the end‐expiratory and end‐inspiratory k‐space binned from GSI data (0.34 ± 0.07, 0.33 ± 0.05) are significantly lower with statistical significance (p < 0.05) than that binned from SeqI data (0.44 ± 0.11, 0.42 ± 0.12). Ringing artifacts are substantially reduced in the dynamic images of eight subjects acquired using the proposed technique in comparison with that acquired using the conventional SeqI technique.ConclusionRinging artifacts in the motion‐resolved images induced by diaphragm drifting can be reduced using the proposed GSI technique for free‐breathing dynamic pulmonary MRI. This technique has the potential to reduce ringing artifacts in free‐breathing liver and kidney MRI based on full‐echo interleaved 3D radial acquisition.

Abstract Background Synchronous surgery to cure complex abdominal wall hernia and stoma reversal is associated with more morbidity, especially in cases in which a posterior component separation technique is performed. Method We present a case of a 64 years old man with BMI 27.8 kg/m2 with history of perfurated acuted diverticulitis with a previous Hartmann procedure. Results He presents with an incisional hernia M2M5W3 VHWG 3 with a median width of 15 cm. We performed a multi-step preparation for this surgery with botulinic toxin application four weeks before surgery. Intraoperatie we performed a stomal reversion surgery (terminoterminal anastomosis) and correction by Rives-Stoppa-Wantz technique with myofascial flap of rectus muscle. We used a myofascial traction system, which was tightened every 2 minutes. With this system we were able to reduce the defect from 15 to 3 cm and close the abdominal wall without the need for posterior component separation technique. Patient was discharged by the 5th day. Conclusion Myofascial relaxation and traction appears to contribute to a tension-free closure of the abdominal wall leading to slower morbidity rates.

This article looks at the group approach to shared dreams following previous publications, including Dreams In Group Psychotherapy: Theory and Technique (Neri et al. 2002) and further papers1, and a natural extension to a 2022 publication (Friedman, 2022). One innovative perspective is the notion that it is often a ‘collective preoccupation’ which starts a group’s shared elaboration process (dreaming), which to begin with is transmitted through interpersonal and transpersonal communication to a delegated dreamer. Another new perspective is to view dreaming (mental digestion) as the main process of a revised four step ‘dream cycle’. The dream cycle goes from collective preoccupation, through personal dreaming, then through an inner narrative, followed by a potentially shared relational elaboration. This helps to understand that ‘dreamtelling’ is only the fourth step in the shared process of mental ‘digestion’ of peoples’ excessive threats/excitements. In Part I I describe the central approach to a shared dream in group analysis as ‘personal responses first’, meaning the predilection of a free-floating discussion of a dream, involving the whole group’s conscious and unconscious mirroring and resonance, while postponing traditional interpretation. Dreams should be understood as both the result and the motor of group processes. Through the joint elaboration of collective preoccupations, dreams that are shared can contribute to the reciprocal healing of relation disorders and dysfunctional relational patterns. I will describe the four-step ‘dream cycle’, which changes the location of mental digestion. By putting transpersonal and interpersonal communication into action, the individual’s and the group’s mind develops (Köhncke and Mies, (2012)). In the final phase, preoccupying situations and conflictual emotions in dreams are elaborated by free discussion, ‘personal responses first’ which is ‘open communication’ in relational configurations in the ‘society of individuals’ (Elias,1939). This process, which I call ‘dreamtelling’, describes discourse (Schlapobersky, 1993) with potential partners who will ‘(re)dream the dream’, and offer further digestion of the collective preoccupation. A series of clinical vignettes discuss notions such as ‘the location of elaboration’ moves in the relations, e.g. ‘dreaming for others’ and ‘delegation’ as well as the notion of an ‘inner group’ and the unconscious communication between dreamers and listeners. In Part II, I provide deeper exploration of a clinical example in group-analytic group therapy, describing group work with a dream. The uniqueness of the group-analytic approach to the dream’s contents and its communicative aspect will be stressed. Requests for containment preoccupy relations and participants and should be differentiated during the discourse of ‘dreamtelling’.

Brain tumor is one of the major causes of death among other types of the cancer because Brain is a very sensitive, complex and central part of the body. Proper and timely diagnosis can prevent the life of a person to some extent. Therefore, in this paper we have introduced brain tumor detection system based on combining wavelet statistical texture features and recurrent neural network (RNN). Basically, the system consists of four phases such as (i) feature extraction (ii) feature selection (iii) classification and (iii) segmentation. First, noise removal is performed as the preprocessing step on the brain MR images. After that texture features (both the dominant run length and co-occurrence texture features) are extracted from these noise free MR images. The high number of features is reduced based on sparse principle component analysis (SPCA) approach. The next step is to classify the brain image using Recurrent Neural Network (RNN). After classification, proposed system extracts tumor region from MRI images using modified region growing segmentation algorithm (MRG). This technique has been tested against the datasets of different patients received from muthu neuro center hospital. The experimentation result proves that the proposed system achieves the better result compared to the existing approaches

ABSTRACTWe used an electronic speckle pattern interferometer (ESPI) for nondestructive measurement in-situ displacement fields in microsystems. A four-step phase-shift technique and magnifier with long working distance were adopted to increase displacement resolution to ∼10−2 μm and spatial resolution to ∼2 μm. A thermal vacuum chamber was designed to induce thermal treatments, including annealing. From the identification of the residual-stress-free state, we quantitatively modeled thermal strains/stress fields, relaxation stresses during annealing, and residual stress fields. Thermoelasticity theory was applied to model the relationship between the relaxation stresses and the displacements measured by ESPI during the evolution of the residual-stress-free state. We assessed the surface residual stress fields of indented bulk Cu; a Fe-Ni lead frame of 100 μm width; and 0.5 μm Au film. In the indented Cu, the normal and shear residual stresses around the indented point range from –1.7 GPa to 700 MPa and –800 MPa to 600 MPa, respectively, and the residual stress in the bending area of the Fe-Ni lead frame was estimated at 148 MPa and verified using beam-bending theory. In the Au film, tensile residual stresses are uniformly distributed from 500 MPa to 800 MPa as verified by X-ray diffraction.

Aberrations and multiple scattering in biological tissues critically distort light beams into highly complex speckle patterns. In this regard, digital optical phase conjugation (DOPC) is a promising technique enabling in-depth focusing. However, DOPC becomes challenging when using fluorescent guide stars for four main reasons: the low photon budget available, the large spectral bandwidth of the fluorescent signal, the Stokes shift between the emission and the excitation wavelength, and the absence of reference beam preventing holographic measurement. Here, we demonstrate the possibility to focus a laser beam through multiple-scattering samples by measuring speckle fields in a single acquisition step with a reference-free, high-resolution wavefront sensor. By taking advantage of the large spectral bandwidth of forward multiply scattering samples, digital fluorescence phase conjugation is achieved to focus a laser beam at the excitation wavelength while measuring the broadband speckle field arising from a micrometer-sized fluorescent bead.

AbstractNi‐free Ti‐based bulk metallic glasses (BMGs) are exciting materials for biomedical applications because of their outstanding biocompatibility and advantageous mechanical properties. The glassy nature of BMGs allows them to be shaped and patterned via thermoplastic forming (TPF). This work demonstrates the versatility of the TPF technique to create micro‐ and nano‐patterns and hierarchical structures on Ti40Zr10Cu34Pd14Sn2 BMG. Particularly, a hierarchical structure fabricated by a two‐step TPF process integrates 400 nm hexagonal close‐packed protrusions on 2.5 µm square protuberances while preserving the advantageous mechanical properties from the as‐cast material state. The correlations between thermal history, structure, and mechanical properties are explored. Regarding biocompatibility, Ti40Zr10Cu34Pd14Sn2 BMGs with four surface topographies (flat, micro‐patterned, nano‐patterned, and hierarchical‐structured surfaces) are investigated using Saos‐2 cell lines. Alamar Blue assay and live/dead analysis show that all tested surfaces have good cell proliferation and viability. Patterned surfaces are observed to promote the formation of longer filopodia on the edge of the cytoskeleton, leading to star‐shaped and dendritic cell morphologies compared with the flat surface. In addition to potential implant applications, TPF‐patterned Ti‐BMGs enable a high level of order and design flexibility on the surface topography, expanding the available toolbox for studying cell behavior on rigid and ordered surfaces.

AbstractProtein electrochemistry represents a powerful technique for investigating the function and structure of proteins. Currently available biochemical assays provide limited information related to the conformational state of proteins and high costs. This work provides novel insights into the electrochemical investigation of the metalloprotein p53 and its redox products using label-free direct electrochemistry and label-based antibody-specific approaches. First, the redox activities of different p53 redox products were qualitatively investigated on carbon-based electrodes. Then, focusing on the open p53 isoform (denatured p53), a quantitative analysis was performed, comparing the performances of different bulk and nanostructured materials (carbon and platinum). Overall, four different p53 products could be successfully discriminated, from wild type to denatured. Label-free analysis suggested a single electron exchange with electron transfer rate constants on the order of 1 s−1. Label-based analysis showed decreasing affinity of pAb240 towards denatured, oxidized and nitrated p53. Furthermore, platinum nanostructured electrodes showed the highest enhancement of the limit of detection in the quantitative analysis (100 ng/ml). Overall, the obtained results represent a first step towards the implementation of highly requested complex integrated devices for clinical practices, with the aim to go beyond simple protein quantification.

Abstract An American option gives the holder the right, but not the obligation, to buy/sell an underlying asset from/to the writer at an agreed strike price at any time on or before the expiry date. Options are mainly used for speculation and hedging. The pricing of options is a fundamental problem in mathematical finance. One of the attractions of options is that they can be used to construct a wide range of trading strategies characterized by different payoff functions. As a preliminary step in the valuation of American options for a variety of trading strategies, in this article the pricing of perpetual American options with general payoffs is considered, where the perpetual American call and put are special cases. Four broad classes of payoff functions are identified for which analytical pricing formulas can be derived by utilizing a Mellin transform technique and an optimization procedure. Depending on the class of payoff functions considered, free boundary problems with one or two boundaries are obtained. Illustrative examples are provided and benchmarked numerically with the binomial method. The characterization of different payoffs for perpetual American options considered in this article will be instrumental in the identification and pricing of new free boundary problems for (non-perpetual) American-style financial derivatives.

OBJECTIVE The authors aimed to review the frontal lobe’s surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results. METHODS Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis. RESULTS Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months. CONCLUSIONS Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

Background Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention vary from fingerprick glucose testing to the provision of continuous glucose monitoring (CGM) to machine learning (ML) driven glucose forecasting. Recent trends for ML have had limited success in preventing free-living hypoglycaemia, due to a focus on increasingly accurate glucose forecasts and a failure to acknowledge the human in the loop and the essential step of changing behaviour. The wealth of evidence from the fields of behaviour change and persuasive technology (PT) allows for the creation of a theory-informed and technologically considered approach. Objectives We aimed to create a PT that would overcome the identified barriers to hypoglycaemia prevention for those with CHI to focus on proactive prevention rather than commonly used reactive approaches. Methods We used the behaviour change technique taxonomy and persuasive systems design models to create HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-Cgm-HEatmap-Assisted-Technology): a novel approach that presents aggregated CGM data in simple visualisations. The resultant ease of data interpretation is intended to facilitate behaviour change and subsequently reduce hypoglycaemia. Results HYPO-CHEAT was piloted in 10 patients with CHI over 12 weeks and successfully identified weekly patterns of hypoglycaemia. These patterns consistently correlated with identifiable behaviours and were translated into both a change in proximal fingerprick behaviour and ultimately, a significant reduction in aggregated hypoglycaemia from 7.1% to 5.4% with four out of five patients showing clinically meaningful reductions in hypoglycaemia. Conclusions We have provided pilot data of a new approach to hypoglycaemia prevention that focuses on proactive prevention and behaviour change. This approach is personalised for individual patients with CHI and is a first step in changing our approach to hypoglycaemia prevention in this group.

Bio-inspired superhydrophobic coatings have been demonstrated to be promising anticorrosion materials. However, developing robust superhydrophobic coatings through simple one-step fluorine-free procedures to meet various functional requirements remains a major challenge. In this study, we fabricated an eco-friendly superhydrophobic Al2O3@PDMS composite coating with mechanical robustness based on Al2O3 NPs, PDMS, and spray coating technique. To characterize surface morphologies, chemical compositions, surface wettability, and anticorrosion properties, FE-SEM, EDS, XPS, contact angle meter, electrochemical impendence spectroscopy, and potentiodynamic polarization techniques were employed. The electrochemical results show that |Z|0.01 Hz and Rct values of the superhydrophobic Al2O3@PDMS coating were four orders of magnitude higher than bare Q235 carbon steel, indicating a significant improvement in corrosion resistance. Furthermore, the deliquescence behaviors of NaCl salt particles and the instantaneous self-coalescence phenomenon were recorded under high atmospheric humidity to suggest that a superhydrophobic surface with Cassie–Baxter interfacial contacts can serve as an efficient barrier to suppress the formation of saline liquid thin films and protect the underlying substrate from corrosion. This robust superhydrophobic Al2O3@PDMS coating is expected to be easily applied to a variety of substrates and to find potential applications for liquid repellency, self-cleaning, corrosion resistance, and other properties.

Introduction: Root canal preparation is an important step of endodontic therapy. For successful endodontic therapy apical extrusion of debris through the apical foramen into the periradicular region should be minimal to avoid postoperative complication such as flare-ups. Aim: To evaluate in-vitro, extrusion of apical debris from the root canal using continuous rotary files (using multiple files system and single rotary file system), reciprocating file system and hand files. Materials and Methods: This in-vitro research was carried out in the Department of Conservative Dentistry and Endodontics, MM college of Dental Sciences and Research, Mullana, Ambala, Haryana, India, from November 2017 to January 2018. A total of 120 human mandibular premolar teeth that were caries free and single-rooted were split into four groups (each group with n=30) Group I: Hand ProTaper, Group II: Protaper Universal, Group III: F360 and Group IV: WaveOne Gold file system. The root canal was instrumented according to manufacturer’s Instructions; and standardised irrigation with distilled water was performed. The Myers and Montgomery’s Model was employed to gather irrigant and debris that had been apically ejected. The analysis of data obtained was done using Post-hoc Bonferroni test, Oneway Analysis of Variance (ANOVA) and paired t-test. Results: The findings indicate that all instrumentation techniques produced significant amount of extruded debris and irrigant. The mean apical debris extrusion using the One-way ANOVA test showed significant difference (p-value<0.001). WaveOne Gold file group showed least (0.0005±0.0001 mg) and Hand ProTaper file showed maximum (0.0017±0.0002) apical debris and irrigant extrusion. Conclusion: Less apical extrusion of irrigant and debris was observed in the engine-driven nickel-titanium systems than manual technique. Reciprocating file system when compared with hand and continuous rotary file system showed less debris extrusion.

Abstract Background Protection of the palatal wound is an essential step following harvesting a palatal soft tissue graft. The aim of the current pilot randomized clinical study was to assess the efficacy of using propylene mesh as protective sheet when compared to conventional custom made acrylic stent after harvesting a palatal graft. The primary outcome of this study was bleeding postoperatively and secondary outcomes were pain, healing profile of the donor site as well as patient satisfaction. Methods Between 2018 and 2019 we conducted a prospective randomized controlled trial of 24 patients with palatal defects. Two groups of 12 patients with 24 sites were included in this study and were treated with soft tissue grafting technique using free grafts harvested from the hard palate. The palatal wounds were protected with propylene mesh (test group) or custom-made acrylic palatal stent (control group). Participants were assessed for the amount and duration of bleeding, pain duration, and the risk of infection 2, 4, 6, 8, 14 days post-operatively. The trial had been registered in clinical trials.gov (NCT04348279). Results Four sites were excluded from the study as dropouts. The polypropylene mesh was more effective at reducing bleeding by (2.4 ± 1.075) and pain by (1.600 ± 0.516), while the custom-made acrylic stent reduced the bleeding (5.8 ± 1.22) and pain (7.100 ± 0.316). The decline in amount of bleeding amount (P value = 0.021) and its duration (P value = 0.001) achieved by the propylene mesh was statistically significant. There was no statistical significant difference in patient satisfaction and the duration of healing process between the 2 groups. However, the healing profile of the test group was statistically significant when compared with the control group (P value = 0.002). Conclusions Propylene mesh is a promising material for protection of the palatal wound due to its light weight, limited bacterial wicking, tissue compatibility. Further studies are required to adequally assess the benefits of this material in periodontal plastic surgeries.

Image-guided surgery, prosthetic-based virtual planning, 3D printing, and CAD/CAM technology are changing head and neck ablative and reconstructive surgical oncology. Due to quality-of-life improvement, dental implant rehabilitation could be considered in every patient treated with curative intent. Accurate implant placement is mandatory for prosthesis long-term stability and success in oncologic patients. We present a prospective study, with a novel workflow, comprising 11 patients reconstructed with free flaps and 56 osseointegrated implants placed in bone flaps or remnant jaws (iliac crest, fibula, radial forearm, anterolateral thigh). Starting from CT data and jaw plaster model scanning, virtual dental prosthesis was designed. Then prosthetically driven dental implacement was also virtually planned and transferred to the patient by means of intraoperative infrared optical navigation (first four patients), and a combination of conventional static teeth supported 3D-printed acrylic guide stent, intraoperative dynamic navigation, and augmented reality for final intraoperative verification (last 7 patients). Coronal, apical, and angular deviation between virtual surgical planning and final guided intraoperative position was measured on each implant. There is a clear learning curve for surgeons when applying guided methods. Initial only-navigated cases achieved low accuracy but were comparable to non-guided freehand positioning due to jig registration instability. Subsequent dynamic navigation cases combining highly stable acrylic static guides as reference and registration markers result in the highest accuracy with a 1–1.5-mm deviation at the insertion point. Smartphone-based augmented reality visualization is a valuable tool for intraoperative visualization and final verification, although it is still a difficult technique for guiding surgery. A fixed screw-retained ideal dental prosthesis was achieved in every case as virtually planned. Implant placement, the final step in free flap oncological reconstruction, could be accurately planned and placed with image-guided surgery, 3D printing, and CAD/CAM technology. The learning curve could be overcome with preclinical laboratory training, but virtually designed and 3D-printed tracer registration stability is crucial for accurate and predictable results. Applying these concepts to our difficult oncologic patient subgroup with deep anatomic alterations ended in comparable results as those reported in non-oncologic patients.

This article on ‘Micro-machining: An Overview (Part II)’ is in continuation to ‘Micro-machining: An Overview (Part I)’ published in this journal ( Journal of Micromanufacturing). It consists of four parts, namely, electrochemical micro-texturing, electrochemical spark micro-machining, molecular dynamics simulation and sustainability issues of micro-machining processes. Electrochemical micro-texturing (ECMTex) deals with various techniques developed for micro-texturing on different types of workpiece-surfaces, namely, flat, curved and free-form surfaces. Here, basically two categories of techniques have been reviewed, namely, with mask and without mask. It also deals with ‘single point tool micro-texturing’ which turns out to be a single-step technique requiring minimum time, but the accuracy and repeatability obtained after micro-texturing need to be critically analysed. For mass production, one needs to go for sinking kind of ECMTex processes. Electrochemical spark micro-machining (ECSMM) is an interesting hybrid (ECM+EDM) process which can be applied for electrically conducting as well as electrically non-conducting materials. However, the work reported in this article deals only with the electrically non-conducting materials for which this process was initially developed. This process has a lot of potential for theoretical work to be done. In this article, two theories of sparking/discharging have been briefly mentioned: single bubble discharging/sparking and single surface discharging. It also dicusses its applications for different types of electrically non-conducting materials. Molecular dynamics simulation (MDS) of micro-/nano-machining processes is very important, but it is very cumbersome to understand at atomic/molecular scale. In these processes, the material behaviour at micro-/nano-level machining is completely different as compared to bulk-machining (macro-machining) processes. Hence, some fundamentals of MDS have been discussed. It just gives the idea of available techniques, softwares and models for different types of processes. However, there is the need of further research work to be done for clearly understanding the MDS of micro-/nano-machining. In the end, the sustainability of micro-machining issues have been discussed, mainly based on the energy consumption per unit mass of production. It is concluded that the advanced micro-manufacturing processes are highly energy-intensive processes, and they need further studies to be done for making them more suitable from sustainability point of view. At the end of each section, some potential areas of research for enhancing the accuracy and repeatability, and minimising the production time of each process have been discussed.

Photo by 14825144 © Alita Xander | Dreamstime.com ABSTRACT The US government's approach to the War on Drugs has created laws to deter people from using illicit drugs through negative punishment. These laws have not controlled illicit drug use, nor has it stopped the opioid pandemic from growing. Instead, these laws have created a negative bias surrounding addiction and have negatively affected particularly vulnerable patient populations, including pregnant women with substance use disorder and newborns with neonatal abstinence syndrome. This article highlights some misconceptions and underscores the challenges they face as they navigate the justice and healthcare systems while also providing possible solutions to address their underlying addiction. INTRODUCTION Pregnant women with substance use disorder require treatment that is arguably for the benefit of both the mother and the fetus. Some suggest that addiction is a choice; therefore, those who misuse substances should not receive treatment. Proponents of this argument emphasize social and environmental factors that lead to addiction but fail to appreciate how chronic substance use alters the brain’s chemistry and changes how it responds to stress, reward, self-control, and pain. The medical community has long recognized that substance use disorder is not simply a character flaw or social deviance, but a complex condition that requires adequate medical attention. Unfortunately, the lasting consequences of the War on Drugs have created a stigma around addiction medicine, leading to significant treatment barriers. There is still a pervasive societal bias toward punitive rather than rehabilitative approaches to addiction. For example, many women with substance use disorder lose custody of their baby or face criminal penalties, including fines and jail time.[1] These punitive measures may cause patients to lose trust in their physicians, ultimately leading to high-risk pregnancies without prenatal care, untreated substance misuse, and potential lifelong disabilities for their newborns.[2] As a medical student, I have observed the importance of a rehabilitative approach to addiction medicine. Incentivizing pregnant women with substance use disorder to safely address their chronic health issues is essential for minimizing negative short-term and long-term outcomes for women and their newborns. This approach requires an open mind and supportive perspective, recognizing that substance use disorder is truly a medical condition that requires just as much attention as any other medical diagnosis.[3] BACKGROUND The War on Drugs was a government-led initiative launched in 1970 by President Richard M. Nixon with the aim of curtailing illegal drug use, distribution, and trade by imposing harsher prison sentences and punishments.[4] However, it is worth noting that one can trace the roots of this initiative back further. In 1914, Congress enacted the Harrison Narcotics Tax Act to target the recreational use of drugs such as morphine and opium.[5] Despite being in effect for over four decades, the War on Drugs failed to achieve its intended goals. In 2011, the Global Commission on Drug Policy released a report that concluded that the initiative had been futile, as “arresting and incarcerating tens of millions of these people in recent decades has filled prisons and destroyed lives and families without reducing the availability of illicit drugs or the power of criminal organizations.”[6] One study published in the International Journal of Drug Policy in the same year found that funding drug law enforcement paradoxically contributed to increasing gun violence and homicide rates.[7] The Commission recommended that drug policies focus on reducing harm caused by drug use rather than solely on reducing drug markets. Recognizing that many drug policies were of political opinion, it called for drug policies that were grounded in scientific evidence, health, security, and human rights.[8] Unfortunately, policy makers did not heed these recommendations. In 2014, Tennessee’s legislature passed a “Fetal Assault Law,” which made it possible to prosecute pregnant women for drug use during pregnancy. If found guilty, pregnant women could face up to 15 years in prison and lose custody of their child. Instead of deterring drug use, the law discouraged pregnant women with substance use disorder from seeking prenatal care. This law required medical professionals to report drug use to authorities, thereby compromising the confidentiality of the patient-physician relationship. Some avoided arrest by delivering their babies in other states or at home, while others opted for abortions or attempted to go through an unsafe withdrawal prior to receiving medical care, sacrificing the mother's and fetus's wellbeing. The law had a sunset provision and expired in 2016. During the two years this law was in effect, officials arrested 124 women.[9] The fear that this law instilled in pregnant women with substance use disorder can still be seen across the US today. Many pregnant women with substance use disorders stated that they feared testing positive for drugs. Due to mandatory reporting, they were not confident that physicians would protect them from the law.[10] And if a woman tried to stop using drugs before seeking care to avoid detection, she often ended up delaying or avoiding care.[11] The American College of Obstetricians and Gynecologists (ACOG) recognizes the fear those with substance use disorders face when seeking appropriate medical care and emphasizes that “obstetric–gynecologic care should not expose a woman to criminal or civil penalties, such as incarceration, involuntary commitment, loss of custody of her children, or loss of housing.”[12] Mandatory reporting strains the patient-physician relationship, driving a wedge between the doctor and patient. Thus, laws intended to deter people from using substances through various punishments and incarceration may be doing more harm than good. County hospitals that mainly serve lower socioeconomic patients encounter more patients without consistent health care access and those with substance use disorders.[13] These hospitals are facing the consequences of the worsening opioid pandemic. At one county hospital where I recently worked, there has been a dramatic increase in newborns with neonatal abstinence syndrome born to mothers with untreated substance use disorders during pregnancy. Infants exposed to drugs prenatally have an increased risk of complications, stillbirth, and life-altering developmental disabilities. At the hospital, I witnessed Child Protective Services removing two newborns with neonatal abstinence syndrome from their mother’s custody. Four similar cases had occurred in the preceding month. In the days leading up to their placement with a foster family, I saw both newborns go through an uncomfortable drug withdrawal. No baby should be welcomed into this world by suffering like that. Yet I felt for the new mothers and realized that heart-wrenching custody loss is not the best approach. During this period, I saw a teenager brought to the pediatric floor due to worsening psychiatric symptoms. He was born with neonatal abstinence syndrome that neither the residential program nor his foster family could manage. His past psychiatric disorders included attention deficit disorder, conduct disorder, major depressive disorder, anxiety disorder, disruptive mood dysregulation disorder, intellectual developmental disorder, and more. During his hospitalization, he was so violent towards healthcare providers that security had to intervene. And his attitude toward his foster parents was so volatile that we were never sure if having them visit was comforting or agitating. Throughout his hospital course, it was difficult for me to converse with him, and I left every interview with him feeling lost in terms of providing an adequate short- and long-term assessment of his psychological and medical requirements. What was clear, however, was that his intellectual and emotional levels did not match his age and that he was born into a society that was ill-equipped to accommodate his needs. Just a few feet away from his room, behind the nurses’ station, were the two newborns feeling the same withdrawal symptoms that this teenager likely experienced in the first few hours of his life. I wondered how similar their paths would be and if they would exhibit similar developmental delays in a few years or if their circumstance may follow the cases hyped about in the media of the 1980s and 1990s regarding “crack babies.” Many of these infants who experienced withdrawal symptoms eventually led normal lives.[14] Nonetheless, many studies have demonstrated that drug use during pregnancy can adversely impact fetal development. Excessive alcohol consumption can result in fetal alcohol syndrome, characterized by growth deficiency, facial structure abnormalities, and a wide range of neurological deficiencies.[15] Smoking can impede the development of the lungs and brain and lead to preterm deliveries or sudden infant death syndrome.[16] Stimulants like methamphetamine can also cause preterm delivery, delayed motor development, attention impairments, and a wide range of cognitive and behavioral issues.[17] Opioid use, such as oxycodone, morphine, fentanyl, and heroin, may result in neonatal opioid withdrawal syndrome, in which a newborn may exhibit tremors, irritability, sleeping problems, poor feeding, loose stools, and increased sweating within 72 hours of life.[18] In 2014, the American Association of Pediatrics (AAP) reported that one newborn was diagnosed with neonatal abstinence syndrome every 15 minutes, equating to approximately 32,000 newborns annually, a five-fold increase from 2004.[19] The AAP found that the cost of neonatal abstinence syndrome covered by Medicaid increased from $65.4 million to $462 million from 2004 to 2014.[20] In 2020, the CDC published a paper that showed an increase in hospital costs from $316 million in 2012 to $572.7 million in 2016.[21] Currently, the impact of the COVID-19 pandemic on the prevalence of newborns with neonatal abstinence syndrome is unknown. I predict that the increase in opioid and polysubstance use during the pandemic will increase the number of newborns with neonatal abstinence syndrome, thereby significantly increasing the public burden and cost.[22] In the 1990s, concerns arose about the potentially irreparable damage caused by intrauterine exposure to cocaine on the development of infants, which led to the popularization of the term “crack babies.”[23] Although no strong longitudinal studies supported this claim at the time, it was not without merit. The Maternal Lifestyle Study (NCT00059540) was a prospective longitudinal observational study that compared the outcomes of newborns exposed to cocaine in-utero to those without.[24] One of its studies revealed one month old newborns with cocaine exposure had “lower arousal, poorer quality of movements and self-regulation, higher excitability, more hypertonia, and more nonoptimal reflexes.”[25] Another study showed that at one month old, heavy cocaine exposure affected neural transmission from the ear to the brain.[26] Long-term follow up from the study showed that at seven years old, children with high intrauterine cocaine exposure were more likely to have externalizing behavior problems such as aggressive behavior, temper tantrums, and destructive acts.[27] While I have witnessed this behavior in the teenage patient during my pediatrics rotation, not all newborns with intrauterine drug exposure are inevitably bound to have psychiatric and behavioral issues later in life. NPR recorded a podcast in 2010 highlighting a mother who used substances during pregnancy and, with early intervention, had positive outcomes. After being arrested 50 times within five years, she went through STEP: Self-Taught Empowerment and Pride, a public program that allowed her to complete her GED and provided guidance and encouragement for a more meaningful life during her time in jail. Her daughter, who was exposed to cocaine before birth, had a normal childhood and ended up going to college.[28] From a public health standpoint, more needs to be done to prevent the complications of substance misuse during pregnancy. Some states consider substance misuse (and even prescribed use) during pregnancy child abuse. Officials have prosecuted countless women across 45 states for exposing their unborn children to drugs.[29] With opioid and polysubstance use on the rise, the efficacy of laws that result in punitive measures seems questionable.[30] So far, laws are not associated with a decrease in the misuse of drugs during pregnancy. Millions of dollars are being poured into managing neonatal abstinence syndrome, including prosecuting women and taking their children away. Rather than policing and criminalizing substance use, pregnant women should get the appropriate care they need and deserve. I. Misconception One: Mothers with Substance Use Disorder Can Get an Abortion If an unplanned pregnancy occurs, one course of action could be to terminate the pregnancy. On the surface, this solution seems like a quick fix. However, the reality is that obtaining an abortion can be challenging due to two significant barriers: accessibility and mandated reporting. Abortion laws vary by state, and in Tennessee, for instance, abortions are banned after six weeks of gestation, typically when fetal heart rhythms are detected. An exception to this is in cases where the mother's life is at risk.[31] Unfortunately, many women with substance use disorders are from lower socioeconomic backgrounds and cannot access pregnancy tests, which could indicate they are pregnant before the six-week cutoff. If a Tennessee woman with substance use disorder decides to seek an abortion after six weeks, she may need to travel to a neighboring state. However, this is not always a feasible option, as the surrounding states (WV, MO, AR, MI, AL, and GA) also have restrictive laws that either prohibit abortions entirely or ban them after six weeks. Moreover, she may be hesitant to visit an obstetrician for an abortion, as some states require physicians by law to report their patients' substance use during pregnancy. For example, Virginia considers substance use during pregnancy child abuse and mandates that healthcare providers report it. This would ultimately limit her to North Carolina if she wants to remain in a nearby state, but she must go before 20 weeks gestation.[32] For someone who may or may not have access to reliable transportation, traveling to another state might be impossible. Without resources or means, these restrictive laws have made it incredibly difficult to obtain the medical care they need. II. Misconception Two: Mothers with SUD are Not Fit to Care for Children If a woman cannot take care of herself, one might wonder how she can take care of another human being. Mothers with substance use disorders often face many adversities, including lack of economic opportunity, trauma from abuse, history of poverty, and mental illness.[33] Fortunately, studies suggest keeping mother and baby together has many benefits. Breastfeeding, for example, helps the baby develop a strong immune system while reducing the mother’s risk of cancer and high blood pressure.[34] Additionally, newborns with neonatal abstinence syndrome who are breastfed by mothers receiving methadone or buprenorphine require less pharmacological treatment, have lower withdrawal scores, and experience shorter hospital stays.[35] Opioid concentration in breastmilk is minimal and does not pose a risk to newborns.[36] Moreover, oxytocin, the hormone responsible for mother-baby bonding, is increased in breastfeeding mothers, reducing withdrawal symptoms and stress-induced reactivity and cravings while also increasing protective maternal instincts.[37] Removing an infant from their mother’s care immediately after birth would result in the loss of all these positive benefits for both the mother and her newborn. The newborns I observed during my pediatrics rotation probably could have benefited from breastfeeding rather than bottle feeding and being passed around from one nurse to the next. They probably would have cried less and suffered fewer withdrawal symptoms had they been given the opportunity to breastfeed. And even if the mothers were lethargic and unresponsive while going through withdrawal, it would still have been possible to breastfeed with proper support. Unfortunately, many believe mothers with substance use disorder cannot adequately care for their children. This pervasive societal bias sets them up for failure from the beginning and greatly inhibits their willingness to change and mend their relationship with their providers. It is a healthcare provider’s duty to provide non-judgmental care that prioritizes the patient’s well-being. They must treat these mothers with the same empathy and respect as any other patient, even if they are experiencing withdrawal. III. Safe Harbor and Medication-Assisted Treatment Addiction is like any other disease and society should regard treatment without stigma. There is no simple fix to this problem, given that it involves the political, legal, and healthcare systems. Punitive policies push pregnant women away from receiving healthcare and prevent them from receiving beneficial interventions. States need to enact laws that protect these women from being reported to authorities. Montana, for example, passed a law in 2019 that provides women with substance use disorders safe harbor from prosecution if they seek treatment for their condition.[38] Medication-assisted treatment with methadone or buprenorphine is the first line treatment option and should be available to all pregnant women regardless of their ability to pay for medical care.[39] To promote continuity of care, health officials could include financial incentives to motivate new mothers to go to follow-up appointments. For example, vouchers for groceries or enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) may offset financial burdens and allow a mother to focus on taking care of her child and her recovery. IV. Mandated Substance Abuse Programs Although the number of people sentenced to state prisons for drug related crimes has been declining, it is still alarming that there were 171,300 sentencings in 2019.[40] Only 11 percent of the 65 percent of our nation’s inmates with substance use disorder receive treatment, implying that the other 89 percent were left without much-needed support to overcome their addiction.[41] It is erroneous to assume that their substance use disorder would disappear after a period without substance use while behind bars. After withdrawal, those struggling with substance use disorder may still have cravings and the likelihood of relapsing remains high without proper medical intervention. Even if they are abstinent for some time during incarceration, the underlying problem persists, and the cycle inevitably continues upon release from custody. In line with the recommendations by Global Commission on Drug Policy and the lessons learned from the failed War on Drugs, one proposed change in our criminal justice system would be to require enrollment and participation in assisted alcohol cessation programs before legal punishment. Policy makers must place emphasis on the safety of the patient and baby rather than the cessation of substance use. This would incentivize people to actively seek medical care, restore the patient-physician relationship, and ensure that they take rehabilitation programs seriously. If the patient or baby is unsafe, a caregiver could intervene while the patient re-enrolls in the program. Those currently serving sentences in prisons and jails can treat their substance use disorder through medication assisted treatment, cognitive behavioral therapy, and programs like Self Taught Empowerment and Pride (STEP). Medication assisted treatment under the supervision of medical professionals can help inmates achieve and maintain sobriety in a healthy and safe way. Furthermore, cognitive behavioral therapy can help to identify triggers and teach healthier coping mechanisms to prepare for stressors outside of jail. Finally, multimodal empowerment programs can connect people to jobs, education, and support upon release. People often leave prisons and jail without a sense of purpose, which can lead to relapse and reincarceration. Structured programs have been shown to decrease drug use and criminal behavior by helping reintegrate productive individuals into society.[42] V. Medical Education: Narcotic Treatment Programs and Suboxone Clinics Another proactive approach could be to have medical residency programs register with the Drug Enforcement Administration (DEA) as Narcotic Treatment Programs and incorporate suboxone clinics into their education and rotations. Rather than family medicine, OB/GYN, or emergency medicine healthcare workers having to refer their patients to an addiction specialist, they could treat patients with methadone for maintenance or detoxification where they would deliver their baby. Not only would this educate and prepare the future generation of physicians to handle the opioid crisis, but it would allow pregnant women to develop strong patient-physician relationships. CONCLUSION Society needs to change from the mindset of tackling a problem after it occurs to taking a proactive approach by addressing upstream factors, thereby preventing those problems from occurring in the first place. Emphasizing public health measures and adequate medical care can prevent complications and developmental issues in newborns and pregnant women with substance use disorders. Decriminalizing drug use and encouraging good health habits during pregnancy is essential, as is access to prenatal care, especially for lower socioeconomic patients. Many of the current laws and regulations that policy makers initially created due to naïve political opinion and unfounded bias to serve the War on Drugs need to be changed to provide these opportunities. To progress as a society, physicians and interprofessional teams must work together to truly understand the needs of patients with substance use disorders and provide support from prenatal to postnatal care. There should be advocation for legislative change, not by providing an opinion but by highlighting the facts and conclusions of scientific studies grounded in scientific evidence, health, security, and human rights. There can be no significant change if society continues to view those with substance use disorders as underserving of care. Only when the perspective shifts to compassion can these mothers and children receive adequate care that rehabilitates and supports their future and empowers them to raise their children. - [1] NIDA. 2023, February 15. Pregnant People with Substance Use Disorders Need Treatment, Not Criminalization. https://nida.nih.gov/about-nida/noras-blog/2023/02/pregnant-people-substance-use-disorders-need-treatment-not-criminalization [2] Substance Use Disorder Hurts Moms and Babies. National Partnership for Women and Families. June 2021 [3] All stories have been fictionalized and anonymized. [4] A History of the Drug War. Drug Policy Alliance. https://drugpolicy.org/issues/brief-history-drug-war [5] The Harrison Narcotic Act (1914) https://www.druglibrary.org/Schaffer/library/studies/cu/cu8.html [6] The War on Drugs. The Global Commission on Drug Policy. Published June 2011. https://www.globalcommissionondrugs.org/reports/the-war-on-drugs [7] Werb D, Rowell G, Guyatt G, Kerr T, Montaner J, Wood E. Effect of drug law enforcement on drug market violence: A systematic review. Int J Drug Policy. 2011;22(2):87-94. doi:10.1016/j.drugpo.2011.02.002 [8] Global Commission on Drug Policy, 2011 [9] Women NA for P. Tennessee’s Fetal Assault Law: Understanding its impact on marginalized women - New York. Pregnancy Justice. Published December 14, 2020. https://www.pregnancyjusticeus.org/tennessees-fetal-assault-law-understanding-its-impact-on-marginalized-women/ [10] Roberts SCM, Nuru-Jeter A. Women’s perspectives on screening for alcohol and drug use in prenatal care. Womens Health Issues Off Publ Jacobs Inst Womens Health. 2010;20(3):193-200. doi:10.1016/j.whi.2010.02.003 [11] Klaman SL, Isaacs K, Leopold A, et al. Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance. J Addict Med. 2017;11(3):178-190. doi:10.1097/ADM.0000000000000308 [12] Substance Abuse Reporting and Pregnancy: The Role of the Obstetrician–Gynecologist. https://www.acog.org/en/clinical/clinical-guidance/committee-opinion/articles/2011/01/substance-abuse-reporting-and-pregnancy-the-role-of-the-obstetrician-gynecologist [13] R. Ghertner, G Lincoln The Opioid Crisis and Economic Opportunity: Geographic and Economic Trends. ASPE. Office of Assistant Secretary for Planning and Evaluation. DHHS Revised September 11, 2018 https://aspe.hhs.gov/reports/economic-opportunity-opioid-crisis-geographic-economic-trends [14] Midon, M. Z., Gerzon, L. R., & de Almeida, C. S. (2021). Crack and motor development of babies living in an assistance shelter. ABCS Health Sciences, 46, e021215-e021215. And for example, see Crack Babies: Twenty Years Later : NPR https://www.npr.org/templates/story/story.php?storyId=126478643 [15] Williams JF, Smith VC, the Committee on Substance Abuse. Fetal Alcohol Spectrum Disorders. Pediatrics. 2015;136(5):e20153113. doi:10.1542/peds.2015-3113 [16] CDC Tobacco Free. Smoking During Pregnancy. Centers for Disease Control and Prevention. Published April 11, 2022. https://www.cdc.gov/tobacco/basic_information/health_effects/pregnancy/index.htm [17] Abuse NI on D. What are the risks of methamphetamine misuse during pregnancy? National Institute on Drug Abuse. https://nida.nih.gov/publications/research-reports/methamphetamine/what-are-risks-methamphetamine-misuse-during-pregnancy [18] CDC. Basics About Opioid Use During Pregnancy | CDC. Centers for Disease Control and Prevention. Published July 21, 2021. https://www.cdc.gov/pregnancy/opioids/basics.html [19] Honein MA, Boyle C, Redfield RR. Public Health Surveillance of Prenatal Opioid Exposure in Mothers and Infants. Pediatrics. 2019;143(3):e20183801. doi:10.1542/peds.2018-3801 [20] Winkelman TNA, Villapiano N, Kozhimannil KB, Davis MM, Patrick SW. Incidence and Costs of Neonatal Abstinence Syndrome Among Infants with Medicaid: 2004–2014. Pediatrics. 2018;141(4):e20173520. doi:10.1542/peds.2017-3520 [21] Strahan AE, Guy GP Jr, Bohm M, Frey M, Ko JY. Neonatal Abstinence Syndrome Incidence and Health Care Costs in the United States, 2016. JAMA Pediatr. 2020;174(2):200-202. doi:10.1001/jamapediatrics.2019.4791 [22] Ghose R, Forati AM, Mantsch JR. Impact of the COVID-19 Pandemic on Opioid Overdose Deaths: a Spatiotemporal Analysis. J Urban Health Bull N Y Acad Med. 2022;99(2):316-327. doi:10.1007/s11524-022-00610-0 [23] Mayes LC, Granger RH, Bornstein MH, Zuckerman B. The Problem of Prenatal Cocaine Exposure: A Rush to Judgment. JAMA. 1992;267(3):406-408. doi:10.1001/jama.1992.03480030084043 [24] NICHD Neonatal Research Network. The Maternal Lifestyle Study. clinicaltrials.gov; 2016. https://clinicaltrials.gov/ct2/show/study/NCT00059540 [25] Lester BM, Tronick EZ, LaGasse L, et al. The maternal lifestyle study: effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants. Pediatrics. 2002;110(6):1182-1192. doi:10.1542/peds.110.6.1182 [26] Lester BM, Lagasse L, Seifer R, et al. The Maternal Lifestyle Study (MLS): effects of prenatal cocaine and/or opiate exposure on auditory brain response at one month. J Pediatr. 2003;142(3):279-285. doi:10.1067/mpd.2003.112 [27] Bada HS, Bann CM, Bauer CR, et al. Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study). Neurotoxicol Teratol. 2011;33(1):78-87. doi:10.1016/j.ntt.2010.06.005 [28] N, P, R. Crack Babies: Twenty Years Later. NPR. Published May 3, 2010. https://www.npr.org/templates/story/story.php?storyId=126478643 [29] Miranda L, Dixon V, September CRP on, 30, 2015. How States Handle Drug Use During Pregnancy http://projects.propublica.org/graphics/maternity-drug-policies-by-state [30] NCDAS: Substance Abuse and Addiction Statistics [2023]. NCDAS. https://drugabusestatistics.org/ [31] (Tenn. Code Ann. § 39-15-216). [32] Institute G. Interactive Map: US Abortion Policies and Access After Roe. https://states.guttmacher.org/policies/ [33] Whitesell M, Bachand A, Peel J, Brown M. Familial, Social, and Individual Factors Contributing to Risk for Adolescent Substance Use. J Addict. 2013;2013:579310. doi:10.1155/2013/579310 [34] CDC. Five Great Benefits of Breastfeeding. Centers for Disease Control and Prevention. Published July 27, 2021. https://www.cdc.gov/nccdphp/dnpao/features/breastfeeding-benefits/index.html [35] Welle-Strand GK, Skurtveit S, Jansson LM, Bakstad B, Bjarkø L, Ravndal E. Breastfeeding reduces the need for withdrawal treatment in opioid-exposed infants. Acta Paediatr. 2013;102(11):1060-1066. doi:10.1111/apa.12378 [36] Ilett KF, Hackett LP, Gower S, Doherty DA, Hamilton D, Bartu AE. Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment. Breastfeed Med Off J Acad Breastfeed Med. 2012;7:269-274. doi:10.1089/bfm.2011.0096 [37] Pedersen CA, Smedley KL, Leserman J, et al. Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects. Alcohol Clin Exp Res. 2013;37(3):484-489. doi:10.1111/j.1530-0277.2012.01958.x [38] Montana SB0289. https://leg.mt.gov/bills/2019/billhtml/SB0289.htm [39] Mullins N, Galvin SL, Ramage M, Gannon M, Lorenz K, Sager B, Coulson CC. Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. J Addict Med. 2020 May/Jun;14(3):185-192. doi: 10.1097/ADM.0000000000000562. PMID: 31567599. [40] Drug Related Crime Statistics [2023]: Offenses Involving Drug Use. NCDAS. https://drugabusestatistics.org/drug-related-crime-statistics/ [41] Association APH. Online only: Report finds most U.S. inmates suffer from substance abuse or addiction. Nations Health. 2010;40(3):E11-E11. [42] Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) | NIDA Archives. Published January 17, 2018. http://archives.nida.nih.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus. Methodology: Twenty-eight Wistar Albino rats were randomised into four groups as control (C), diabetic (DC), diabetic with hepatic ischemia-reperfusion injury (DIR), and diabetic but administered dexmedetomidine followed by hepatic IRI (DIRD) groups. Hepatic tissue samples were evaluated histopathologically by semiquantitative methods. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathion s-transpherase (GST), and catalase (CAT) enzyme levels were investigated in liver and kidney tissues as oxidative state parameters. Results: In Group DIR; hepatocyte degeneration, sinusoidal dilatation, pycnotic nucleus, and necrotic cells were found to be more in rat hepatic tissue; while mononuclear cell infiltration was higher in the parenchyme. MDA levels were significantly lower; but SOD levels were significantly higher in Group DIRD with regard to Group DIR. In the IRI induced diabetic rats’ hepatic and nephrotic tissues MDA levels, showing oxidative injury, were found to be lower. SOD levels, showing early antioxidant activity, were higher. Conclusion: The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease IRI. Key words: Hepatic ischemia reperfusion injury; Diabetes mellitus; Dexmedetomidine; Rat; MDA; SOD Citation: Sezen SC, Işık B, Bilge M, Arslan M, Çomu FM, Öztürk L, Kesimci E, Kavutçu M. Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats. Anaesth Pain & Intensive Care 2016;20(2):143-149 Received: 21 November 2015; Reviewed: 10, 24 December 2015, 9, 10 June 2016; Corrected: 12 December 2015; Accepted: 10 June 2016 INTRODUCTİON Perioperative acute tissue injury induced by ischemia-reperfusion is a comman clinical event caused by reduced blood supply to the tissue being compromised during major surgery. Ischemia leads to cellular injury by depleting cellular energy deposits and resulting in accumulation of toxic metabolites. The reperfusion of tissues that have remained in ischemic conditions causes even more damage.1 Furthermore hepatic ischemia-reperfusion injury (IRI) demonstrates a strong relationship with peri-operative acute kidney injury.2 The etiology of diabetic complications is strongly associated with increased oxidative stress (OS). Diabetic patients are known to have a high risk of developing OS or IRI which results with tissue failure.3 The most important role in ischemia and reperfusion is played by free oxygen radicals.1 In diabetes, characterized by hyperglycemia, even more free oxygen radicals are produced due to oxidation of glucose and glycosylation of proteins.3 The structures which are most sensitive to free oxygen radicals in the cells are membrane lipids, proteins, nucleic acids and deoxyribonucleic acids.1 It has been reported that endogenous antioxidant enzymes [superoxide dismutase (SOD), glutathion s-transpherase (GST), catalase (CAT)] play an important role to alleviate IRI.4-8 Also some pharmacological agents have certain effects on IRI.1 The anesthetic agents influence endogenous antioxidant systems and free oxygen radical formation.9-12 Dexmedetomidine is a selective α-2 adrenoceptor agonist agent. It has been described as a useful and safe adjunct in many clinical applications. It has been found that it may increase urine output by considerably redistributing cardiac output, inhibiting vasopressin secretion and maintaining renal blood flow and glomerular filtration. Previous studies demonstrated that dexmedetomidine provides protection against renal, focal cerebral, cardiac, testicular, and tourniquet-induced IRI.13-18 Arslan et al observed that dexmedetomidine protected against lipid peroxidation and cellular membrane alterations in hepatic IRI, when given before induction of ischemia.17 Si et al18 demonstrated that dexmedetomidine treatment results in a partial but significant attenuation of renal demage induced by IRI through the inactivation of JAK/STAT signaling pathway in an in vivo model. The efficacy of the dexmedetomidine for IRI in diabetic patient is not resarched yet. The purpose of this experimental study was to evaluate the biochemical and histological effects of dexmedetomidine on hepatic IRI in diabetic rat’s hepatic and renal tissue. METHODOLOGY Animals and Experimental Protocol: This study was conducted in the Physiology Laboratory of Kirikkale University upon the consent of the Experimental Animals Ethics Committee of Kirikkale University. All of the procedures were performed according to the accepted standards of the Guide for the Care and Use of Laboratory Animals. In the study, 28 male Wistar Albino rats, weighing between 250 and 300 g, raised under the same environmental conditions, were used. The rats were kept under 20-21 oC at cycles of 12-hour daylight and 12-hour darkness and had free access to food until 2 hours before the anesthesia procedure. The animals were randomly separated into four groups, each containing 7 rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (Sigma Chemical, St. Louis, MO, USA) at a dose of 65 mg/kg body weight. The blood glucose levels were measured at 72 hrs following this injection. Rats were classified as diabetic if their fasting blood glucose (FBG) levels exceeded 250 mg/dl, and only animals with FBGs of > 250 mg/dl were included in the diabetic groups (dia­betes only, diabetes plus ischemia-reperfusion and diabetes plus dexmedetomidine-ischemia-reperfusion). The rats were kept alive 4 weeks after streptozotocin injection to allow development of chronic dia­betes before they were exposed to ischemia-reperfusion.(19) The rats were weighed before the study. Rats were anesthetized with intraperitoneal ketamine 100 mg/kg. The chest and abdomen were shaved and each animal was fixed in a supine position on the operating table. The abdomen was cleaned with 1% polyvinyl iodine and when dry, the operating field was covered with a sterile drape and median laparotomy was performed. There were four experimental groups (Group C (sham-control; n = 7), (Group DC (diabetes-sham-control; n = 7), Group DIR (diabetes-ischemia-reperfusion; n = 7), and Group DIRD (diabetes-ischemia-reperfusion-dexmedetomidine; n = 7). Sham operation was performed on the rats in Group C and Group DC. The sham operation consisted of mobilization of the hepatic pedicle only. The rats in this group were sacrificed 90 min after the procedure. Hepatic I/R injury was induced in Groups DIR and DIRD respectively with hepatic pedicle clamping using a vascular clamp as in the previous study of Arslan et al.(17) After an ischemic period of 45 min, the vascular clamp was removed. A reperfusion period was maintained for 45 min. In Group DIRD, dexmedetomidine hydrochloride 100 μg/kg, (Precedex 100 μg/2 ml, Abbott®, Abbott Laboratory, North Chicago, Illinois, USA) was administrated via intraperitoneal route 30 minutes before surgery. All the rats were given ketamine 100 mg/kg intraperitoneally and intracardiac blood samples were obtained. Preserving the tissue integrity by avoiding trauma, liver and renal biopsy samples were obtained. Biochemical Analysis: The liver and renal tissues were first washed with cold deionized water to discard blood contamination and then homogenized in a homogenizer. Measurements on cell contest require an initial preparation of the tissues. The preparation procedure may involve grinding of the tissue in a ground glass tissue blender using a rotor driven by a simple electric motor. The homogenizer as a tissue blender similar to the typical kitchen blender is used to emulsify and pulverize the tissue (Heidolph Instruments GMBH & CO KGDiax 900 Germany®) at 1000 U for about 3 min. After centrifugation at 10,000 g for about 60 min, the upper clear layer was taken. MDA levels were determined using the method of Van Ye et al,(20) based on the reaction of MDA with thiobarbituric acid (TBA). In the TBA test reaction, MDA and TBA react in acid pH to form a pink pigment with an absorption maximum at 532 nm. Arbitrary values obtained were compared with a series of standard solutions (1,1,3,3-tetraethoxypropane). Results were expressed as nmol/mg.protein. Part of the homogenate was extracted in ethanol/chloroform mixture (5/3 v/v) to discard the lipid fraction, which caused interferences in the activity measurements of T-SOD, CAT and GST activities. After centrifugation at 10.000 x g for 60 min, the upper clear layer was removed and used for the T-SOD, CAT, GST enzyme activity measurement by methods as described by Durak et al21, Aebi22 and Habig et al23 respectively. One unit of SOD activity was defined as the enzyme protein amount causing 50% inhibition in NBTH2 reduction rate and result were expressed in U/mg protein. The CAT activity method is based on the measurement of absorbance decrease due to H2O2 consumption at 240 nm. The GST activity method is based on the measurement of absorbance changes at 340 nm due to formation of GSH-CDNB complex. Histological determinations: Semiquantitative evaluation technique used by Abdel-Wahhab et al(24) was applied for interpreting the structural changes investigated in hepatic tissues of control and research groups. According to this, (-) (negative point) represents no structural change, while (+) (one positive point) represents mild, (++) (two positive points) medium and (+++) (three positive points) represents severe structural changes. Statistical analysis: The Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA) 20.0 softwre was used for the statistical analysis. Variations in oxidative state parameters, and histopathological examination between study groups were assessed using the Kruskal-Wallis test. The Bonferroni-adjusted Mann-Whitney U-test was used after significant Kruskal-Wallis to determine which groups differed from the others. Results were expressed as mean ± standard deviation (Mean ± SD). Statistical significance was set at a p value < 0.05 for all analyses. RESULTS There was statistically significant difference observed between the groups with respect to findings from the histological changes in the rat liver tissue (hepatocyte degeneration, sinüsoidal dilatation, pycnotic nucleus, prenecrotic cell) determined by light microscopy according to semiquantitative evaluation techniques (p < 0.0001). In Group DIR, hepatocyte degeneration was significantly high compared to Group C, Group DC and Group DIRD (p < 0.0001, p < 0.0001, p = 0.002, respectively), (Table 1, Figure 1-4). Similarly, sinüsoidal dilatation was significantly higher in Group DIR (p < 0.0001, p = 0.004, p = 0.015, respectively). Although, pcynotic nucleus was decreased in Group DIRD, it did not make a significant difference in comparison to Group DIR (p = 0.053), (Table 1, Figure 1-4). The prenecrotic cells were significantly increased in Group DIR, with respect to Group C, Group DC and Group DIRD (p < 0.0001, p = 0.004, p < 0.0001, respectively), (Table 1, Figure 1-4). Table 1. The comparison of histological changes in rat hepatic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR Figure 1: Light microscopic view of hepatic tissue of Group C (control). VC: vena centralis, *: sinusoids. ®: hepatocytes, k: Kupffer cells, G: glycogen granules, mc: minimal cellular changes, Hematoxilen & Eosin x 40 Figure 2: Light-microscopic view of hepatic tissue of Group DC (diabetes mellitus control) (G: Glycogen granules increased in number, (VC: vena centralis, *:sinusoids. ®:hepatocytes, k:Kupffer cells, G: glycogen granules, mc: minimal cellular changes; Hematoxylin & Eosin x 40) Figure 3: Light-microscopic view of hepatic tissue of Group DIR (Diabetes Mellitus and ischemia-reperfusion) (VC: vena centralis, (H) degenerative and hydrophic hepatocytes, (dej) vena centralis degeneration (centrolobar injury) (*): sinusoid dilatation. (←) pycnotic and hyperchromatic nuclei, MNL: mononuclear cell infiltration, (¯) congestion, K: Kupffer cell hyperplasia, (­) vacuolar degeneration (Hematoxylin & Eosin x 40) Figure 4: Light-microscopic view of hepatic tissue of Group DIRD (Diabetes Mellitus and ischemia-reperfusion together with dexmedetomidine applied group) (VC: vena centralis, (MNL) mononuclear cell infiltration, (dej) hydrophilic degeneration in hepatocytes around vena centralis, (conj) congestion, G: glycogen granules, (←) pycnotic and hyperchromatic nuclei, sinusoid dilatation (*) (Hematoxylin & Eosin x 40) Besides, in liver tissue parenchyma, MN cellular infiltration was a light microscopic finding; and showed significant changes among the groups (p < 0.0001). This was significantly higher in Group DIR, compared to Group C, DC, and DIRD (p < 0.0001, p=0.007, p = 0.007, respectively), (Table 1, Figure 1-4). The enzymatic activity of MDA, SOD and GST in hepatic tissues showed significant differences among the groups [(p = 0.019), (p = 0.034). (p = 0.008) respectively]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p = 0.011, p = 0.016, respectively), (Table 2). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.010, p = 0.038, respectively), (Table 2). The GST enzyme activity was significantly higher in Group DIR, when compared to Group C, DC and DIRD (p = 0.007, p = 0.038, p = 0.039, respectively), (Table 2). Table 2. Oxidative state parameters in rat hepatic tissue [Mean ± SD] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR The enzymatic activity of MDA, SOD in renal tissues, showed significant differences among the groups [(p < 0.0001), (p = 0.008) respectively ]. MDA enzyme activity was significantly incresed in Group DIR, according to Group C and Group DIRD (p < 0.0001, p < 0.0001, respectively). Also MDA enzyme activity level was significantly increased in Group DC, in comparison to Group C and Group DIRD (p = 0.003, p = 0.001, respectively), (Table 3). In Group DIR SOD enzyme activity was lower with respect to Group C and Group DIRD (p = 0.032, p = 0.013, respectively), (Table 3). The GST enzyme activity was significantly higher in Group DIR than the other three groups, however; CAT levels were similar among the groups (Table 3). Table 3: Oxidative state parameters in rat nephrotic tissue [Mean ± SD)] p**: Statistical significance was set at a p value < 0.05 for Kruskal-Wallis test *p < 0.05: When compared with Group DIR DISCUSSION In this study, we have reported the protective effect of dexmedetomidine in experimental hepatic and renal IRI model in the rat by investigating the MDA and SOD levels biochemically. Besides, hepatic histopathological findings also supported our report. Ischemic damage may occur with trauma, hemorrhagic shock, and some surgical interventions, mainly hepatic and renal resections. Reperfusion following ischemia results in even more injury than ischemia itself. IRI is an inflammatory response accompanied by free radical formation, leucocyte migration and activation, sinusoidal endothelial cellular damage, deteoriated microcirculation and coagulation and complement system activation.1 We also detected injury in hepatic and renal tissue caused by reperfusion following ischemia in liver. Experimental and clinical evidence indicates that OS is involved in both the pathogenesis and the complications of diabetes mellitus.25,26 Diabetes mellitus is a serious risk factor for the development of renal and cardiovascular disease. It is also related to fatty changes in the liver.27 Diabetes-related organ damage seems to be the result of multiple mechanisms. Diabetes has been associated with increased free radical reactions and oxidant tissue damage in STZ-induced diabetic rats and also in patients.26Oxidative stress has been implicated in the destruction of pancreatic β-cells28 and could largely contribute to the oxidant tissue damage associated with chronic hyperglycemia.29 A number of reports have shown that antioxidants can attenuate the complications of diabetes in patients30 and in experimental models.28,31 This study demonstrated that diabetes causes a tendency to increase the IRI. There is a lot of investigations related to the pharmacological agents or food supplements applied for decreasing OS and IRI. Antioxidant agents paly an important role in IRI by effecting antioxidant system or lessening the formation of ROS. It has been reported that anesthetic agents too, are effective in oxidative stress.1 During surgical interventions, it seems rational to get benefit from anesthetic agents in prevention of OS caused by IRI instead of using other agents. It has been declared that; dexmedetomidine; as an α-2 agonist with sedative, hypnotic properties; is important in prevention of renal, focal, cerebral, cardiac, testicular and tourniquet-induced IRI.13-18 On the other hand Bostankolu et al. concluded that dexmedetomidine did not have an additional protective role for tournique induced IRI during routine general anesthesia.32 In this study; we have shown that dexmedetomidine has a reducing effect in IRI in diabetic rats. Some biochemical tests and histopathological evaluations are applied for bringing up oxidative stress and IRI in the tissues. Reactive oxygen species (ROS) that appear with reperfusion injury damage cellular structures through the process of the lipid peroxidation of cellular membranes and yield toxic metabolites such as MDA.33 As an important intermidiate product in lipid peroxidation, MDA is used as a sensitive marker of IRI.34 ROS-induced tissue injury is triggered by various defense mechanisms.35 The first defence mechanisms include the antioxidant enzymes of SOD, CAT, and GPx. These endogenous antioxidants are the first lines of defence against oxidative stres and act by scavenging potentially damaging free radical moieties.36 There is a balance between ROS and the scavenging capacity of antioxidant enzymes.1-8 In this study, for evaluation of oxidative damage and antioxidant activity, MDS, SOD, GST and CAT levels were determined in liver and kidney tissues. MDA levels in hepatic and renal tissues were higher in Group DIR compared to Group C and Group DIRD. GST levels were higher in Group DIR compared to all the other three groups. When the groups were arranged from highest to lowest order, with respect to CAT levels, the order was; Group DIR, Group DIRD, Group DC and Group C. However, the difference was not significant. The acute phase reactant MDA, as a marker of OS, was found to be high in Group DIR and low in Group DIRD. This could be interpreted as the presence of protective effect of dexmedetomidine in IRI. IRI developing in splanchnic area causes injury also in the other organs.35 Leithead et al showed that clinically significant hepatic IRI demonstrates a strong relationship with peri-operative acute kidney injury.2 In our experimental research that showed correlation to that of research by Leithead et al. After hepatic IRI in diabetic rats renal OS marker MDA levels were significantly more in Group DIR than Group DIRD. In our study, we observed histopathological changes in the ischemic liver tissue and alterations in the level of MDA, SOD, GST and CAT levels which are OS markers. Histopathological changes of the liver tissues are hepatocyt degeneration, sinusoidal dilatation, nuclear picnosis, celluler necrosis, mononuclear cell infiltrationat paranchimal tissue. These histopathological injury scores were significantly lower in the Group DIRD than those in group DIR. LIMITATION Study limitation is there was no negative control group, as this type of surgical intervention is not possible in rats without anesthesia. CONCLUSION The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease ischemia-reperfusion injury. Conflict of interest and funding: The authors have not received any funding or benefits from industry or elsewhere to conduct this study. 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Cut In 1964, William S. Burroughs' Nova Express is published. Part of the trilogy of books Burroughs wrote in the early 1960s (The Soft Cell and The Ticket That Exploded are the other two), Nova Express explores the problems that technology creates in the information age; and the ways in which language and thought have come under the influence of mass media. The book begins with a broad declaration against consumerism and corporate control: Listen all you boards syndicates and governments of the earth. And you powers behind what filth deals consummated in what lavatory to take what is not yours. To sell the ground from unborn feet forever - "For God's sake don't let that Coca-Cola thing out -" (Nova Express 3) Rather than opt for conventional narrative as a means of uncovering the problems ideology brings with media-driven mass consumption, in the early '60s, Burroughs develops a method of writing he calls "the cut-up". The cut-up method entails taking a page of writing (a newspaper, a poem, a novel, an advertisement, a speech) and cutting it down the middle twice so that four sections remain. One then rearranges the sections in random order to create a new page. Variations of the four section cut are permissible and can lead to further juxtapositions. The purpose of the cut-up is to disclose ideological positions within media, to recontextualise the language of media often taken for granted as natural and not as a socially and economically constructed act. Information has become addictive, Burroughs says, invoking the junkie as a metaphor for mass consumption. Its addictive state leads to hallucinations, distortions of what is real and what is illusion; what do we need to live, and what do we buy for mere consumption. The scanning pattern we accept as "reality" has been imposed by the controlling power on this planet, a power primarily oriented towards total control - In order to retain control they have moved to monopolize and deactivate the hallucinogen drugs by effecting noxious alternations on a molecular level. (Nova Express 53) The cut-up provides a means to combat the "junky" in us all by revealing the powers of technology. In the end, the cut-up leads to a collagist practice of juxtaposition. As Burroughs and collaborator Byron Gysin explained in a later work, The cut-up method brings to writers the collage, which has been used by painters for fifty years. And used by the moving and still camera. In fact all street shots from movie or still cameras are by the unpredictable factors of passersby and juxtaposition cut-ups (Burroughs and Gysin 29). Through its structure, Nova Express is a lesson in making cut-ups, a demonstration of how power might be undermined in the digital age. Paste In 1964, the Center for Contemporary Cultural Studies at Birmingham began. Influenced by Raymond Williams' 1958 Culture and Society, the Birmingham School legitimized the reading of popular culture as a means to uncovering dominant ideologies and power structures within institutional systems. In particular, the center proposed structuring scholasticism so that the study of media texts would allow for the questioning of social and political practices. The Birmingham school advised that curriculae supplement their agendas with the question of class; the complex relationships between power, which is an easier term to establish in the discourses of culture than exploitation, and exploitation; the question of a general theory which could, in a critical way, connect together in a critical reflection different domains of life, politics, and theory, theory and practice, economic, political ideological questions, and so on; the notion of critical knowledge itself and the production of critical knowledge as a practice. (Hall 279) One of the Birmingham School's first works was Stuart Hall and Paddy Whannel's Popular Arts, which searched out ways to teach media. In particular, Hall and Whannel viewed popular culture as a place to teach the power of ideology. There is, in fact, a growing recognition that the media of mass communication play such a significant role in society, and especially in the lives of young people, that the school must embrace the study of their organization, content, and impact. But there is little agreement about how such studies should be carried out. Just what shall be studied? With what precise purpose? In what relationship to the established subjects? Ultimately the answer will depend upon our attitude towards these media, our social thinking about the kind of society in which they wield their influence and, in particular, our response to the things the media offer - individual films, television programmes, popular songs, etc. (Hall and Whannel 21) Today, the Birmingham School is recognised as the beginning of contemporary cultural studies. It answers Hall and Whannel by using texts from popular culture to uncover the semiotic cultural codes that make up popular discourse. These methods shed light on how supposedly naturally constructed messages contain deeper meanings and purposes. Mix In 1964, DJ Alan Freed was convicted of tax evasion as a result of his involvement in the payola record business scandal of 1962. Considered one of the first rock and roll DJs, Freed is often credited for breaking ‘50s racial barriers by playing African-American music on the airwaves and hosting largely attended African-American dances and concerts. Even though Freed didn't invent the phrase "rock and roll," he credited himself with the term's introduction into music vocabulary, a myth-making act with far reaching implications. As critic Nick Tosch writes: "Though he was certainly not the first who had done so; he was only the most influential of those who had - Freed [had] rinsed the Dixie Peach from its image, rendering it more agreeable to the palate of a greater public" (Tosch 9). In the same year of Freed's conviction, another legendary DJ, Murray the K, found fame again by following the Beatles around on their 1964 North American tour. Murray the K had been popular in the late '50s for "his wild stammering of syllables, fragments of words, black slang, and meaningless, rhythmical burbling" to make transitions between songs (Poschardt 75). Mass copying of Murray the K's DJ stylings led to his redundancy. When New Journalist Tom Wolfe rediscovered the DJ tagging along with the Beatles, he became intrigued, describing him as "the original hysterical disk jockey": Murray the K doesn't operate on Aristotelian logic. He operates on symbolic logic. He builds up an atmosphere of breathless jollification, comic hysteria, and turns it up to a pitch so high it can hypnotize kids and keep them frozen. (Wolfe 34) While Freed introduced African-American culture to mainstream music, Murray the K's DJing worked from a symbolic logic of appropriation: sampled sounds, bits and pieces of eccentric outtakes used as vehicles to move from song to song. Both Freed and Murray the K, however, conceived the idea of the DJ as more than a spinner of records. They envisioned the DJ as a form of media, a myth maker, a composer of ideas through sounds and politics. In a sense, they saw their work as disseminating social commentary on '60s racial politics and ideology, working from a fairly new innovation: the rock and roll record. Their DJ work became the model for contemporary hip hop artists. Instead of considering isolated train whistles or glass crashing (the technique of Murray the K) as sources for sampling, contemporary DJs and digital samplers cut and paste fragments from the history of popular music in order to compose new works, compositions which function as vehicles of cultural critique. Groups like Public Enemy and The Roots utilise their record collections to make political statements on drug usage, economic problems within the African-American community, and racism. For Tricia Rose, these artists are the cultural studies writers of the digital age. "Rappers are constantly taking dominant discursive fragments and throwing them into relief, destabilizing hegemonic discourses and attempting to legitimate counterhegemonic interpretations." (Rose 102) Remix The juxtaposition of these three events in 1964 marks an interesting place to consider the potential for new media and cultural studies. Such a juxtaposition answers the calls of Lawrence Grossberg, Cary Nelson, and Paula Treichler in their introduction to Cultural Studies, a collection of essays from the 1970s and 1980s. The editors suggest that cultural studies can be thought of, in some ways, as a collagist practice. The methodology of cultural studies provides an equally uneasy marker, for cultural studies in fact has no distinct methodology, no unique statistical, ethnomethodological, or textual analysis to call its own. Its methodology, ambiguous from the beginning, could best be seen as a bricolage. (2) For these editors, "Cultural studies needs to remain open to unexpected, unimagined, even uninvited possibilities" (3). To consider cultural studies from the perspective of 1964 is to evoke the unexpected, the unimagined, and the uninvited. It is to resituate the demands of cultural study within the context of new media - the legacy of Burroughs' cut-up reborn in the digital sampler. In response to the editors of Cultural Studies, I propose the practice of temporal juxtaposition as a way of critical writing. My initial juxtaposition of 1964 asserts that to teach such a practice, one must teach cutting and mixing. The Break The break, as a DJ method, is "any short captured sound whatsoever" (Eshun 14). The break motivates digital sampling; it provides the points from which samplers appropriate past works into their own: "Break beats are points of rupture in their former contexts, points at which the thematic elements of a musical piece are suspended and the underlying rhythms brought center stage. In the early stages of rap, these break beats formed the core of rap DJs' mixing strategies" (Rose 73-74). Breaks are determined by how DJs produce cuts in previously recorded music. "The cut is a command, a technical and conceptual operation which cuts the lines of association" (Eshun 16). For William Burroughs, cuts create shock in readers; they are tools for destroying ideology. "Once machine lines are cut, the enemy is helpless" (Ticket That Exploded 111). In Nova Express, Burroughs issues the command, "Cut word lines" (62). And in Naked Lunch, the cut provides a set of reading instructions, a way for readers to uncover Burroughs' own ideological positions. You can cut into Naked Lunch at any intersection point . . . I have written many prefaces. . . Naked Lunch is a blueprint, a How-To Book. (Naked Lunch 224 For Roland Barthes, a major influence on the founding of the Birmingham School, the How-To functioned as a place for cultural critique. Barthes felt that semiotic analysis could break ideological positions constructed in popular culture. Barthes used the How-To as one example of what he called mythologies, items of popular culture assumed to be natural but latent with ideological meanings. He treated the how-to tourist guide (how to enjoy yourself on vacation) as one such place for further analysis. The good natured image of "the writer on holiday" is therefore no more than one of these cunning mystifications which the Establishment practices the better to enslave its writers. (Barthes 30) Mythologies has inspired contemporary cultural studies. Dick Hebdige states that through Barthes' work, "It was hoped that the invisible temporary seam between language, experience and reality could be located and prised open through a semiotic analysis" (Hebdige 10). My juxtapositions of 1964, however, tell me that the How-To for cultural studies is cutting and pasting, not hermeneutical or semiotic analysis (i.e. What does this mean? What do these codes reveal?), which have long been cultural studies' focus. 1964 updates cultural studies practices by reinventing its methods of inquiry. 1964 forces academic study to ask: How would a contemporary cultural critic cut into cultural texts and paste selections into a new media work? The Sample Cuts and breaks become samples, authorial chosen selections. My sample comes from Walter Benjamin, an early DJ of media culture who discovered in 19th century Paris a source for a new compositional practice. Benjamin's unfinished Arcades project proposed that the task of the writer in the age of mechanical reproduction is to become a collector. "The collector was the true inhabitant of the interior" (Benjamin 168). Benjamin felt that the "poets find their refuse on the street" (79) preempting William Gibson's now often cited remark, "the street finds its own use for things" (Gibson 186) and modern DJs who build record collections by rummaging bargain street sales. I find in Benjamin's work a place to sample, a break for cutting into Burroughs' nova method. "The basic nova mechanism is very simple: Always create as many insoluble conflicts as possible and always aggravate existing conflict - This is done by dumping life forms with incompatible conditions of existence on the same planet" (Nova Express 53). Like Burroughs, Benjamin expressed interest in the ideological conflicts created through juxtaposition. His collections of the Parisian Arcades led to a cultural history different from that of the Frankfurt School. The Arcades' juxtapositions of consumer goods and artifacts opposed the Frankfurt School's understandings of Marxism and methods of critique. The conflict I create is that of incorporating the concerns of cultural studies into media study as an alternative practice. This practice is a system of sampling, cutting, breaking, and pasting. What might initially seem incompatible to cultural studies, I propose as a method of critique. My initial juxtaposition of 1964 becomes the first step towards doing so: I critique current cultural studies' methods of semiotic and hermeneutical analysis by way of the cut and mix I create. This Benjamin sample is pasted onto the Networked Writing Environment (NWE) at the University of Florida where I teach media classes in one of several computer networked classrooms. Working from a sampled Benjamin and the juxtaposition of the previously described temporal events of 1964, I see a place to rethink new media and cultural studies. The NWE's graphical user interface completes the cut. Our Unix operating system uses X Windows for desktop display. The metaphor of the X, the slash, the cut, becomes a place to rethink what cultural studies admits to be a cut-up, or a non-unified practice (as stated by Grossberg et al). The X also recalls the crossroads, the iconic marker of the place of decision. Standing at the crossroads, I envision the blues song of the same name, which in 1964 was cut from its Robert Johnson origins and remixed as a new recording by the Yardbirds. This decision shifts the focus of media study to cultural collections, their juxtapositions, and the alternative understandings that surface. The tools of technology (like those we use in the NWE: the Web, MOO, and e-mail) cut the structural dominance of critique and encourage us to make new pedagogical decisions, like juxtaposing a William Burroughs novel with the founding of the Birmingham School with the rise of the DJ. Putting these practices into the mix, we redefine cultural critique. 1964, then, is the place where cultural mixing begins. References Barthes, Roland. Mythologies. New York: Hill and Wang, 1957. Benjamin, Walter. Charles Baudelaire: A Lyric Poet in the Era of High Capitalism. Harry Zohn trans. London: NLB, 1973. Burroughs, William S. Naked Lunch. New York: Grove, 1982 (1959). _________________. Nova Express. New York: Grove, 1992 (1964). _________________. The Ticket That Exploded. New York: Grove, 1987 (1962). Burroughs, William S. and Byron Gysin. The Third Mind. New York: Viking Press, 1978. Eshun, Kodwo. More Brilliant Than the Sun. London: Quartet, 1999. Gibson, William. "Burning Chrome." Burning Chrome. New York: Ace Books, 1981. Grossberg, Lawrence, Cary Nelson, and Paula Treichler, eds. Cultural Studies. London: Routledge, 1992. Hall, Stuart. "Theoretical Legacies." Cultural Studies. Hall, Stuart and Paddy Whannel. The Popular Arts. New York: Pantheon, 1964. Hebdige, Dick. Subculture: The Meaning of Style. London and New York: Routledge, 1979. Poschardt, Ulf. DJ Culture. London: Quartet, 1998. Rose, Tricia. Black Noise: Black Music and Black Culture in Contemporary America.Hanover: Wesleyan University Press, 1994. Tosch, Nick. Unsung Heroes of Rock and Roll. New York: Da Capo Press, 1999. Wolfe, Tom. "The Fifth Beatle." The Kandy Kolored Tangerine Flake Streamlined Baby. New York: Pocket Books, 1965.

Preamble: Medium/Format/Marker Medium/Format/Marker (M/F/M) was a visual-aural improvisational performance involving myself, and musicians Joe Sorbara, and Ben Grossman. It was formed through my work as a PhD candidate at the Improvisation, Community, and Social Practice research initiative at the University of Guelph. This performance was conceived as an attempted intervention against the propensity to reify the “new.” It also sought to address the proliferation of the screen and question how the increased presence of screens in everyday life has augmented the way in which an audience is conceived and positioned. This conception is in direct conversation with my thesis, which is a practice-based research project exploring what the experimental combination of intermediality, improvisation, and the cinema might offer towards developing a reflexive approach to "new" media, screen culture, and expanded cinemas. One of the ways I chose to explore this area involved developing an interface that allowed an audio-visual ensemble to improvise with a film's audio-visual projection. I experimented with different VJ programs. These programs often utilize digital filters and effects to alter images through real-time mixing and layering, much like a DJ does with sound. I found a program developed by Chicago-based artist Ontologist called Ontoplayer, which he developed out of his practice as an improvisational video artist. The program works through a dual-channel interface where two separate digital files could be augmented, with their projected tempo capable of being determined by musicians through a MIDI interface. I conceptualized the performance around the possibility of networking myself with two other musicians via this interface. I approached percussionist Joe Sorbara and multi-instrumentalist Ben Grossman with the idea to use Ontoplayer as a means to improvise with Chris Marker's La Jetée (1962, 28 mins). The film itself would be projected simultaneously in four different formats: 16mm celluloid, VHS, Blu-ray, and Standard Definition video (the format the ensemble improvised with) projected onto four separate screens. From left to right, the first screen contained the projected version of La Jetée that we improvised with, next to it was its Blu-ray format, next to that, a degraded VHS copy of the film, and next to that, the 16mm print. The performance materialized through performing a number of improvisatory experiments. A last minute experiment conceived a few hours before the performance involved placing contact microphones overtop of the motor on a Bell & Howell 16mm projector. The projector was tested in the days leading up to the performance and it ran as smoothly as could be expected. It had a nice cacophonous hum that Ben Grossman intended to improvise with using some contact mics attached directly over the projector’s motor, a $5 iPad app, and his hurdy-gurdy. Fifteen minutes before the performance began, the three of us huddled to discuss how long we'd like to go. We had met briefly the day before to discuss the technical setup of the performance but not its execution and length. I hadn't considered duration. Joe broke the silence by asking if we'd be "finding beginnings and endings." I didn't know what that entailed, but nodded. We started. I turned on the projector and it immediately started to cough and chew on the 40 year old 16mm print I found online. My first impulse was to intervene, to try to save it. The film continued and I sat frozen for a moment. Joe started playing and Ben, expecting me to send him the audio track from La Jetée, prompted me to do so. I let the projector go and began. Joe had a digital kick-drum and two contact mics on his drum kit hooked into a MIDI hub, while Ben's hurdy-gurdy had a contact mic inside it, wired into the hub. The hub hooked into my laptop and allowed for an intermedial conversation to emerge between the three of us. While the 16mm, VHS, and Blu-Ray formats proceeded relatively unimpeded alongside each other on their respective screens, the fourth screen was where this conversation took place. I digitally reordered different image sequences from La Jetée. The fact that it’s a film (almost) comprised entirely of still images made this reordering intriguing in that I was able control the speed of progressing from each image to the next. The movement from image to image was structured between Ben and Joe’s improvisations and the kind of effects and filters I had initialized. Ontoplayer has a number of effects and filters that push the base image into more abstract territories (e.g.: geometric shapes, over pixelation) I was uninterested in exploring. I utilized effects that to some degree still kept the representational content of the image intact. The degree to which these effects took hold of the image were determined by whether or not Ben and Joe decided to use the part of their instrument that would trigger them. The decision to linger on an image, colour it differently, or skip ahead in the film’s real-time projection destabilized my sense of where I was in the film. It became an event in the sense that each movement, both visual and aural was happening with an indeterminate duration. La Jetée opens with the narrator proclaiming: “this is the story of a man marked by an image from his childhood.” The story itself is situated around a man in a post-apocalyptic world, haunted by the persistent memory of a woman he saw as a child while standing on the jetty at Orly Airport in Paris. The man was a soldier, now captured, and imprisoned in an underground camp. The prison guards have been conducting experiments on the prisoners, attempting to use the prisoner’s memories as a mechanism to send them backwards and forwards in time. The narrator explains, “with the surface of the planet irradiated … The human race was doomed. Space was off limits. The only link with survival passed through time … The purpose of the experiments was to throw emissaries into time to call the past and future to the aid of the present.” La Jetée is visually structured as a photomontage, with voice-over narration, diegetic and non-diegetic sound existing as component parts to the whole film. I decided to separate these components for the sake of isolating them before the performance as instruments of the film to be improvisationally deployed through the intermedial connection between Ben, Joe, and myself. The resulting projections that emerged from our interface became a kind of improvised "grooving" to La Jetée that restricted the impulse to discriminately place sound beneath and behind the image. I selected images from different points in the film that felt "timely" given the changing dynamic between the three of us. I remember lingering on an image of the woman's face, her hand against her mouth, her hair being blown back by the wind. I looked and listened for the moment when the film would catch and then catch fire. It never came. We let the reel run to the end and continued on improvising until we found an ending. But the sound of that film catching but never breaking, the intention and tension of the film being near death the entire time made everything we did more precious, teetering on the brink of failure. We could never have predicted that, and it gave us something I continue to ponder and be thankful for. Celluloid junkies in the room commented on how precipitous the whole thing was, given how rare it is to encounter the sound of celluloid film travelling through a projector inside a cinematic space. An audiophile mused over how there wasn’t any document, his mind adequately blown by how “funky” the projector sounded. With there being no document of the performance, I'm left with my own memories. In mining the aftermath of this performance, I hope to find an addendum that considers how improvisation might negotiate with augmentation in ways that speak to Walter Benjamin's assertion that the "camera, the film, on the one hand, extends our comprehension of the necessities which rule our lives; on the other hand, it manages to assure us of an immense and unexpected field of action” (Benjamin 236-7).Images to be Determined I got a job working in a photo lab eight years ago, right around the time digital cameras started becoming not only affordable, but technologically-comparable alternatives to film cameras. The photo printer in the lab was setup to scan and digitize celluloid filmstrips to allow for digital “touchups” by the technician. It was also hooked into touchscreen media stations that accepted a variety of memory card formats so that customers could “touchup” their own images. Celluloid film meant that as long as their format was chemical, touching up their images remained the task of the technician. Against the urging of the lab’s manager, I resisted altering other people’s images. It felt like a violation, despite the fact that almost every customer was unaware of this process. They assumed a degree of responsibility for a chemically-exposed image. I still got blamed for a lot of bad photography, but an image chemically under or overexposed was irreparable. Digital cameras changed all of that. I still preferred an evenly exposed celluloid print to a digital, but the allure was the ability for these images to be augmented. Augmentation is synonymous with "enhancement," "prosthesis," "addition," "amplification," "enrichment," "expansion,” and "extension" (to name a few). For the purpose of this essay, I am situating augmentation as an agential act engaging with a static form to purposefully alter its aesthetic and political relation to a reality. To what extent can we say that the digital image is itself, an augmentation? If Instagram is any indication, the digital image's existence is bound by its perpetual augmentation. A digital image is only as good as its capacity to be worked on. The ubiquity of digitally applying lomographic filters to digital images, as a defining step in their distributive chain, is indicative of the discursive impact remediating the old into the new has on digital forms. These digitally-coded filters used to augment “clear” digital images are comprised of exaggerated imperfections that existed to varying degrees, as unforeseen side effects of working with comparatively more unstable celluloid textures. The filtered images themselves are digital distortions of a digital original. The filters augment this original through obscuring one or a number of components. Some filters might exaggerate the green values or sharpen a particular quadrant within the frame that might coincide with the look of a particular film stock from the past. The discourse of “film” and “vintage” photography has become a synonymous component of the digital aesthetic, discursively warming up what is often considered to be a cold, and disembodied medium. Augmentation works to re-establish a congruous relationship between the filmic and the digital, attempting to reconcile the aesthetic distance between granularity and pixelation. This is ironic because this process is encapsulated through digitally encoding and applying these filters for the sake of obscuring clarity. Thus, the object is both hailed as clear and clearly manipulable. Another example a bit closer to the cinema is the development of digital video cameras offering RAW, or minimally compressed file formats for the sole purpose of augmenting the initial recording in post-production workflows in an attempt to minimize degradation in the image. The colour values and dynamic range of these images are muted, or flattened so that the human can control their elevation after the fact. To some degree the initial image, in itself, is an augmentation of its filmic relative. From early experiments with video synthesizers to the present digital coding of film effects, digital images have tantalized video artists and filmmakers with possibility shrouded in instantaneity and malleability. A key problem with this structure remains the unbridled proliferation and expansion of the digital image, set free for the sake of newness. How might improvisation work towards establishing an ethics of augmentation? An ethics of this kind must disrupt the popular notion of the digital image existing beyond analogical constraints. The belief that “if you can imagine it, you can do it” obfuscates the reality that to work with images, whatever their texture, is a negotiation with constraint. Part of M/F/M’s fruition emerged from a conversation I'd had with Canadian Animator Pierre Hébert last summer. Now obvious, but for Hébert, the first obstacle he needed to overcome as an improviser was developing an instrument that he could gig with. Through the act of designing an instrument I immediately became aware of what wasn't possible, and so the work leading up to the performance involved attempting to expand the possibilities of that instrument. How might I conceive of my own treatment of images simultaneously treated by Joe and Ben as a kind of cinematic extended technique we collaboratively bring into being? Constraint necessitates the need for extension, for finding new ways to sound and appear. Constraint is also consistently conceived as shackling progress. In scientific methodologies it is often arbitrarily imposed to steer an experiment into a desired direction. This sort of experimental methodology is in the business of presupposing outcomes, which I feel is often the case with what ultimately becomes the essay of end result in Humanities research. Constraint is an important imposition in improvisation only if the parties involved are willing to find new ways to move in consort with it. The act of improvisation is thus an engagement with the spatio-temporal constraints of performance, politics, memory, texture, and difference. My conception of the cinema is that of an instrument, whose past is what I work with to better understand its future. Critic Gene Youngblood, in his landmark book, Expanded Cinema, theorized a new conception of the cinema as a global planetary phenomenon suffused inside a space of intermedia, where immersive, interactive, and interconnected realms necessitated the need to critically conceptualise the cinema in cosmic terms. At around the time of Youngblood's writing, another practitioner of the cosmic way, improviser and composer Sun Ra was staking a similar claim for music's ability to uplift the species cosmically. Ra's popular line “If we came from nowhere here, why can’t we go somewhere there?” (Heble 125), articulated the problematic racial politics in post-WWII America, that fixed African-American identity into a static domain with little room to move upward. The "somewhere there" to Ra was a non-space, created from "a desire to opt out of the very codes of representation and intelligibility, the very frameworks of interpretation and assumption which have legitimated the workings of dominant culture" (Heble 125). Though Youngblood's and Ra's intellectual and creative impulses formed from differing political circumstances, the work and thinking of these two figures remain significant articulations of the need to work from and towards the cosmic. In 2003, Youngblood published a follow-up essay in a reprint of Expanded Cinema entitled Cinema and the Code. In it, he defines cinema as a “phenomenology of the moving image.” Rather than conceiving of it through any of its particular media, Youngblood advocates for a segregated conception of the cinema: Just as we separate music from its instruments. Cinema is the art of organizing a stream of audiovisual events in time. It is an event-stream, like music. There are at least four media through which we can practice cinema – film, video, holography, and structured digital code—just as there are many instruments through which we can practice music. (Youngblood cited in Marchessault and Lord 7) Music and cinema are thus conceived as the exterior consequences of creative and co-creative instrumental experimentation. For Ra and Youngblood, the planetary stakes of this project are infused with the need to manufacture and occupy an imaginative space (if only for a moment) outside of the known. This is not to say that the action itself is transcendental. But rather this outside is the planetary. For the past year I've been making a documentary with Joe Sorbara on the free improv scene in Toronto. Listening to musicians talk about improvisation in expansive terms, as this ethereal and ephemeral experience, that exists on the brink of failure, that is as much an act of memory as renewal, reverberated with my own feelings surrounding the cinema. Improvisation, to philosopher Gary Peters, is the "entwinement of preservation and destruction", that "invites us to make a transition from a closed conception of the past to one that re-thinks it as an endlessly ongoing event or occurrence whereby tradition is re-originated (Benjamin) or re-opened (Heidegger)” (Peters 2). This “entwinement of preservation and destruction” takes me back to my earlier discussion of the ways in which digital photography, in particular lomographically filtered snapshots, is structured through preserving the discursive past of film while destroying its standard. The performance of M/F/M attempted to connect the augmentation of the digital image and the impact this augmentation had on conceptualizing the past through an improvisational approach to intermediality. The issue I have with the determination of images concerns their technological standardization. As long as manufacturers and technicians control this process then the practice of gathering, projecting, and experiencing digital images is predetermined by their commercial obligation. It assures that augmenting the “immense and unexpected field of action” comprising the domain of images is itself a predetermination. References Benjamin, Walter. Illuminations. New York: Schocken Books, 1985. Heble, Ajay. Landing on the Wrong Note. London: Routledge, 2000. Marker, Chris, dir. La Jetée. Argos Films. 1962. Marchessault, Janine, and Susan Lord. Fluid Screens, Expanded Cinema. Toronto: University of Toronto Press, 2007. Peters, Gary. The Philosophy of Improvisation. Chicago: University of Chicago Press, 2009.

The western world has an enthusiasm for blondes that amounts to a cultural fetish. As a signifier the blonde is loaded: blondes have more fun, blondes are dumb, blondes are more sexually available, blondes are less capable, less serious, less complicated. The blonde is, in modern day patriarchy, often portrayed as the ideal woman. The Oxford Dictionary defines a Goddess as a female deity or a woman who is adored for her beauty. The Blonde Goddess then is the ultimate contemporary female, worshipped for her appearance, erotically idolised. She may be a Playboy bunny, the hot girl on the beach or the larger than life billboard, but everywhere her image haunts mere mortals: the men who can’t have her and the women who can’t be her. During the second wave of feminism the Blonde Goddess was vilified as an unrealistic illusion and exploitive fantasy and our enthusiasm for her was roundly challenged. She was a stereotype, feminists cried, a site of oppression, a phoney construct. Men were judged harshly for desiring her and women were discouraged from being her. Well beyond hair colour and its power as signifier the very notion of Goddessness, of being adored for one’s beauty, was considered repressive. Women were called upon to refuse participation in blondeness (in its signifying sense) and Goddessness (in the sense of being revered for attractiveness) and men were chastised for being superficial and chauvinistic.Nevertheless, decades later, many men continue to lust after her, women (and increasingly younger girls) work ever harder at being her — bleaching, shaving, breast augmenting and botoxing — and the media promotes endless representations of her. If the second wave thought the Blonde Goddess would give up the ghost easily it was mistaken but what their enthusiastic critique did enable is the birth of a new type of Blonde Goddess, one generally considered to be stronger, more empowered and a better role model for the 21st century Miss. Though the likes of Mae West hinted at this type of Blonde Goddess well before Madonna it was not until Madonna’s generation that she went mainstream. There have been many Blonde Goddess “It girls” — Jean Harlow, Jayne Mansfield and Debbie Harry (singer of the band Blondie) to name a few, but two in particular stand out as the embodiment of these types; their bodies and identities going beyond the image-making machinery to become a kind of Blonde Goddess performance art. They are Marilyn Monroe and Madonna. The enthusiasm for blondeness and Goddessness routinely gives rise to faddish cultural enthusasisms. In Monroe’s day her curvaceous figure was upheld as the model female form. After Madonna appeared with her bangles and layered tops girls all across America and around the world dressed like her. Drawing on Angela Carter’s feminist readings of De Sade in The Sadeian Woman and envisioning Monroe and Madonna, two of the most fêted examples of Blonde Goddessness in history, as De Sade’s Justine and Juliette reveals their erotic currency as both couched in patriarchal gender relations and binding us to it. Considering Monroe and Madonna with the Marquis De Sade characters Justine and Juliette in mind illustrates that Goddessness as I’m defining it here — the enthusiasm which with women rely on beauty for affirmation and men’s enthusiastic feeding of that dependence — amounts to a feminine masquerade that disempowers women from a real experience of femaleness, emancipation and eroticism. When feminists in the 60s and 70s critiqued the Blonde Goddess as the poster-child for good old-fashioned sexism it was women like Monroe they had in mind. What feminists argued for they largely got — access to life beyond the domestic domain, financial autonomy, self-determination — but, as a De Sadian viewing of Madonna will show, we’re still compromised. While many feminists, most notably Andrea Dworkin, rejected the Marquis De Sade, notorious libertine and writer, as a dishonourable pornographer, others, such as Luce Irigaray and Angela Carter, felt he accurately reflected the social structures and relations of western civilisation and was therefore fertile ground for the exploration of what it is to be a woman in our culture. Justine and Juliette are erotic novels that recount the very different fortunes of two dissimilar sisters. They are beautiful (of course) and as such they are Goddesses, even while being defiled and defiling. Monroe and Madonna are metaphorical sisters in a man's world (and it was an infamous touch of video genius when Madonna acknowledged as much by doing Monroe in the video for “Material Girl” early on in her career). Yet one is a survivor and one isn't. One is living and one is long dead. Monroe is the Blonde Goddess as victim; Madonna is the Blonde Goddess as Villain. Monroe cast a shadow; Madonna has danced with the shadow. Both Marilyn and Madonna assumed a feminine masquerade so successful, so omnipotent, that they became not just Goddesses, desired by men, admired by women, and emulated by girls, but the most iconic and celebrated Blonde Goddesses of their age. It was, and in Madonna’s case still is, a highly sexualised masquerade that utilises and promotes itself as a commodity. Both women milked this masquerade to achieve notoriety and wealth in a world where women are disadvantaged in the public sphere. Some read this kind of exploitation of erotic desire as a mark of subjugation while others see it as a feminist act: a knowing usage of means toward a self-possessed end, but as Carter will help demonstrate, masquerade is, either way, an artificial construct and our enthusiasm for trading in it comes at a high price. Monroe, the sexy, fragile child-woman, was the firstborn of the sisters. Her star rose in the moralistic fifties, and by all accounts she spent most of her time in the limelight frustrated by her career and by the studio’s control of it. She was “owned”, and she rebelled against it, fleeing to New York City to study acting at the renowned Actors Studio. She became a devoted student of method acting, a technique that encourages actors to plumb their emotional depths and experiences, though her own psychological instability threatened her career. She was scandalously difficult to work with: chronically late, forgetful, and self-indulgent; and she died alone, intoxicated and naked. Conspiracy theories aside, it seems likely that a cocktail of mental disturbance, man trouble, and substance addiction led to her premature death by overdose in 1962. Monroe’s traditional take on blondeness and Goddessness embodied the purely feminine masquerade and translated to the classic Justine trajectory.Madonna can be thought of as Monroe’s post-modern younger sister, the next generation of Blonde Goddessness. Known for her self-determination, business savvy and self-control Madonna’s self-parody and decades long survival and triumph in a male dominated industry is remarkable. Perhaps this is where the sisters differ most: Madonna challenges the dominant semiotic code of traditional gender roles in that she combines her feminine masquerade with masculinity, witness the pointy cone bra worn with pinstripe trousers and monocle on the “Blonde Ambition” tour. Madonna is the new blonde — shrewder, more forceful, more man-like. She plays girly in her feminine masquerade, but she does so self-consciously, with a wink, as the second sister who has observed and learned the lesson of the first. In Carter’s exploration of the characters of Justine and Juliette she notes that when the orphaned girls are turned out of the convent to fend for themselves, Justine, the sister whose goodness and innocence is constantly met with the brutality and betrayal of men, "embarks on a dolorous pilgrimage in which each preferred sanctuary turns out to be a new prison and all the human relations offered her are a form of servitude" (39). During Monroe’s pilgrimage from foster care, to young wife, to teen model, to star she found herself trapped in an abusive studio system that could not nurture her and instead raped her over and over again in the sense that it thwarted her personal aspirations as an actor and her desire for creative autonomy by overpowering her with its demands. Monroe did not own her own life and sexuality so much as function as a site of objectification, a possession of the Tinsel Town suits. In her personal life she was endowed with the “feminine” trait of feeling; she was, like Justine, "the broken heart, the stabbed dove, the violated sepulcher, the persecuted maiden whose virginity is perpetually refreshed by rape” (Carter 49).In real life and in most of her characters Monroe was kind hearted, generous, caring and compassionate. It is this heart that Justine values most; whatever happens to the body, no matter how impure it becomes, the heart remains sacred. The victim with heart is morally superior to her masters. In a suffering that becomes second nature, "Justine marks the start of a kind of self-regarding female masochism, a woman with no place in the world, no status, the core of whose resistance has been eaten away by self-pity” (57).Conspiracy theories and rumors of Monroe's suffering and possible murder at the hands of the Kennedys (cast as evil Sadian masters) abound. Suicide attempts, drug dependency, and nervous breakdowns were the order of the day in her final years. The continuing fascination with Monroe lies in the fact that she was the archetypal sullied virgin. Feminine virtue and goodness require sexual innocence and purity. If Monroe’s innocence (a feature of films like Some Like it Hot) was too often confused with stupidity she made the most of it by cornering the market on bimbo roles (Gentleman Prefer Blondes is her ultimate dumb blonde performance). But even those who thought she couldn’t act realised that her appeal was potent because her innocence was infused with the potentiality of an uncontainable libidinous energy. Like Justine, Juliette was a woman born into a man's world, but in her corruption Juliette decided beat men at their own game, to transcend her destiny as woman at any cost. Carter says of Juliette: She is rationality personified and leaves no single cell of her brain unused. She will never obey the fallacious promptings of her heart. Her mind functions like a computer programmed to produce two results for herself — financial profit and libidinal gratification. (79)Indeed, it could be said that it is financial profit and libidinal gratification that most defines Madonna in the public’s eye. She is obscenely rich and often cited for her calculated re-inventions and assertive sexuality (which peaked in the early nineties with the album Erotica and the graphic Sex book). Madonna, like Juliette, is a story-teller. Even if she isn’t always the author of her songs she creates narrative interplay using song, fashion, and video. Like Juliette Madonna takes control of her destiny. She heads her own production company and is intimately involved with the details of her multi-faceted career. Like Monroe Madonna is said to have slept around strategically in her pre-stardom years, but unlike Monroe she was not passed around. The men in Madonna’s life early in her career were critical to advancing it. From Dan Gilroy, who helped form her first rock band, the Breakfast Club to DJ John "Jellybean" Benitez, who remixed tracks on her debut album Madonna took every step up the ladder of success guided by a precision instinct for self-preservation and promotion. She was not used up as she used others. Her trail leaves no sign of weakness, just one envelope-pushing accomplishment after another, with a few failures along the way, most notably in film. Though very different central to both Monroe and Madonna’s lives and careers is a mega-watt erotic appeal, an appeal that has everything to do with their respective differential repetitions of being blonde.In Eroticism Georges Bataille defines eroticism as the fusion of separate objects involving the play of discontinuity and continuity. In Bataille’s work these words have a specific and unconventional meaning. Discontinuity describes our individuality, our separateness from each other, a separateness that reigns in our social and work-a-day lives. Continuity refers to dissolution of separateness that is most associated with death but which is also experienced by way of exalted living through a taste of transcendence. Bataille posits three types of eroticism: physical, emotional and religious and he claims that they all “substitute for the individual isolated discontinuity a feeling of profound continuity” (15).Here Bataille meets De Sade. In the Introduction to Eroticism Bataille speaks of De Sade’s assertion that we come closest to death (continuity) through the “licentious image.” Further, Bataille declares that eroticism is not just an enthusiasm; it is the enthusiasm of humankind. “It seems to be assumed that man has his being independently of his passions,” he says. “I affirm, on the other hand, that we must never imagine existence except in terms of these passions” (12). He goes on to state that our enthusiasm/eroticism is not just an aspect of our being, but its driving force: “We are discontinuous beings, individuals who perish in isolation in the midst of an incomprehensible adventure, but we yearn for our lost continuity. We find the state of affairs that binds us to our random and ephemeral individuality hard to bear.” (15).Human beauty is, Bataille suggests, measured by its distance from the animal — the more ethereal (light and unearthly) the female shape and texture, and the less clear its relation to animal reality, the more beautiful — the erotic moment lies in profaning that beauty, reducing it to its animal essence. Perhaps this is another reason why blondeness matters and signifies sex, conferring as it does a halo, an ethereal “light” which evokes the sacredness of continuity while denying the animal (the hairy and base reality of the body). This is the invitation The Blonde Goddess makes to defilement, her begging to be reduced to her private parts. Juliette/Madonna subverts her blonde invitation to be profaned by actively taking part in the profanation. Madonna has openly embraced gay culture, S & M, exhibitionism, fetishism, role-play and religious symbolism placing herself centre stage at all times. Justine/Monroe attracted erotic victimisation while Juliette/Madonna refused it by sleight of hand, and here again De Sade can help make sense of this. The works that illustrate this difference between Justine/Monroe and Juliette/Madonna most clearly are The Misfits and Truth or Dare. The Misfits is a beautiful and delicate film, written by Monroe’s then husband, Arthur Miller. The role of Roslyn is rumored to be based on Monroe's own character and her relationship with its three metaphorically dying cowboys reveals an enchanting and pale Justine broken by the dysfunctional and dominating masculinity around her. In contrast, Truth or Dare is a self styled documentary of Madonna’s “Blonde Ambition” tour. It portrays Madonna striking a pose as the tough-talking Queen of the castle, calling the shots, with a bevy of play-thing pawns scuttling beneath her. But, opposite as these characterisations are, some sameness emanates from the two women in these works. Something haunts the screen and it is this: the sisters’ unavoidable cultural roots as women. Even as Madonna sucks on a bottle in faux fellatio, even as she simulates masturbation on stage or scolds her messy young dancers there is something melancholic about her, a vague relationship to Monroe. And here Carter helps solve the mystery: "She [Juliette] is just as her sister is, a description of a type of female behavior rather than a model of female behavior and her triumph is just as ambivalent as is Justine's disaster. Justine is the thesis, Juliette the antithesis” (79).In other words, in Carters’ view Justine/Monroe as heart personified maintains the traditional role of woman as body, as one belonging to the private sphere who pays dearly for entering public life, while Juliette/Madonna as reason personified infiltrates the male dominated territory of culture. Unlike Monroe, Madonna gets away with being a public figure, flourishes even, but as Carter’s Juliette, this victory has required her to betray herself in some way. It is “ambivalent” and Madonna doesn’t quite get off scot free. Madonna has been progressive in that she moved away from the traditional feminine role of body in a forbidding industry, but even though her lucrative maneuvering is more sophisticated than Monroe’s careening, she walks a fine line. In De Sade the sexuality of a libertine is a male identified desire in which women are objectified and exploited. Madonna’s trick is to manifest in feminine masquerade then take an ironic turn in objectifying and exploiting herself in what amounts to a split persona, half woman, half man. In other words she seduces herself under our gaze, and she dares to enjoy it. Ultimately, neither sister can escape the social structure into which she was born. Monroe, who was unable to live as a real woman, lives on as a legend, a Blonde Goddess in the eternal feminine masquerade. Madonna is reborn every time she re-invents herself but it’s hard to tell, with all the costume changing, who the real Madonna is. It was the unactualised real woman that the second wave tried to free by daring to suggest that she existed and was valuable beyond signification and Goddessness and that she had a right to her own experience of enthusiasm/eroticism rather than being relegated to the role of being the “licentious image” for the male gaze. The attack on the Blonde Goddess underestimated the deeply rooted psychic/emotional conditioning at play on both sides of the Blonde Goddess game. Here we are in a new millennium in which the ‘pornified’ Blonde Goddess is everywhere but even if she’s more unfettered and sexually active that deeply rooted conditioning remains. For Carter neither Justine nor Juliette is a worthy role model for the women of today and it would seem to follow that neither are Monroe nor Madonna. However, Carter does speak of “a future in which might lie the possibility of a synthesis of their modes of being, neither submissive nor aggressive, capable of both thought and feeling” (79). Blondeness as a signifier and Goddessness as a function inhibit an experience of shared enthusiasm and eroticism between men and women. When Bataille speaks of nakedness he means eroticism as the destruction of the self-contained character that gives rise to an experience of continuity. This kind of absolute nakedness is impossible for those trapped in the cycle of signification and functional relations. I suggest that the liberation project of the second wave of feminism stalled when in our desire to not be Justines we simply became more akin to Juliette. Blondeness as a signifier is still problematic, and Goddessness of the kind I have spoken of here — women’s attachment to using beauty to garner adoration in place of an innate sense of self and worth and men’s willingness to patronise it — is still rampant and both the Justine and Juliette feminine masquerades produce a false economy of enthusiasm and eroticism that denies the experience of authenticity and the true potential of relationship. The challenge now is one that most needs to be met not in the spotlight but in the privacy of our own beings and the forum of our lives as the struggle for synthesis continues in those of us, female and male, blonde, brunette, redhead, black or grey-haired, who long for an experience of ourselves and each other that transcends masquerade. ReferencesCarter, Angela. The Sadeian Woman. London: Virago Press, 1979.Bataille, Georges. Eroticism. London: Marion Boyars Publishers, 1987.Madonna. Erotica. Warner Bros, 1992.———. “Material Girl.” Like a Virgin. WEA/Warner Bros, 1984.——— and Steven Meisel. Sex. Warner Bros, 1992. The Misfits. Dir. John Huston.. MGM, 1961. Some Like It Hot. Dir. Billy Wilder, Billy. MGM, 1959. Truth or Dare. Dir. Alek Keshishian. Live/Artisan, 1991.

What creative techniques of resistance are available to a female filmmaker when she is the victim of a violent event and filmed at her most vulnerable? This article uses an autoethnographic lens to discuss my experience of a serious car crash my family and I were inadvertently involved in due to police negligence and a criminal act. Employing Creative Analytical Practice (CAP) ethnography, a reflexive form of research which recognises that the creative process, producer and product are “deeply intertwined” (Richardson, “Writing: A Method” 930), I investigate how the crash’s violent affects crippled my agency, manifested in my creative praxis and catalysed my identification of latent forms of institutionalised violence in film culture, its discourse and pedagogy that also contributed to my inertia. The article maps my process of writing a feature length screenplay during the aftermath of the crash as I set out to articulate my story of survival and resistance. Using this narrative inquiry, in which we can “investigate how we construct the world, ourselves, and others, and how standard objectifying practices...unnecessarily limit us” (Richardson, “Writing: A Method” 924), I outline how I attempted to disrupt the entrenched power structures that exist in dominant narratives of violence in film and challenge my subjugated positioning as a woman within this canon. I describe my engagement with the deconstructionist practices of writing the body and militant feminist cinema, which suggest subversive opportunities for women’s self-determination by encouraging us to embrace our exiled positioning in dominant discourse through creative experimentation, and identify some of the possibilities and limitations of this for female agency. Drawing on CAP ethnography, existentialism, film feminism, and narrative reframing, I assert that these reconstructive practices are more effective for the creative enfranchisement of women by not relegating us to the periphery of social systems and cultural forms. Instead, they enable us to speak back to violent structures in a language that has greater social access, context and impact.My strong desire to tell screen stories lies in my belief that storytelling is a crucial evolutionary mechanism of resilience. Narratives do not simply represent the social world but also have the ability to change it by enabling us to “try to figure out how to live our lives meaningfully” (Ellis 760). This conviction has been directly influenced by my personal story of trauma and survival when myself, my siblings, and our respective life partners became involved in a major car crash. Two police officers attending to a drunken brawl in an inner city park had, in their haste, left the keys in the ignition of their vehicle. We were travelling across a major intersection when the police car, which had subsequently been stolen by a man involved in the brawl – a man who was wanted on parole, had a blood alcohol level three times over the legal limit, and was driving at speeds exceeding 110kms per hour - ran a red light and crossed our path, causing us to crash into his vehicle. From the impact, the small four-wheel drive we were travelling in was catapulted metres into the air, rolling numerous times before smashing head on into oncoming traffic. My heavily pregnant sister was driving our vehicle.The incident attracted national media attention and our story became a sensationalist spectacle. Each news station reported erroneous and conflicting information, one stating that my sister had lost her unborn daughter, another even going so far as to claim my sister had died in the crash. This tabloidised, ‘if it bleeds, it leads’, culture of journalism, along with new digital technologies, encourages and facilitates the normalisation of violent acts, often inflicted on women. Moreover, in their pursuit of high-rating stories, news bodies motivate dehumanising acts of citizen journalism that see witnesses often inspired to film, rather than assist, victims involved in a violent event. Through a connection with someone working for a major news station, we discovered that leading news broadcasters had bought a tape shot by a group of men who call themselves the ‘Paparazzi of Perth’. These men were some of the first on the scene and began filming us from only a few metres away while we were still trapped upside down and unconscious in our vehicle. In the recording, the men are heard laughing and celebrating our tragedy as they realise the lucrative possibilities of the shocking imagery they are capturing as witnesses pull us out of the back of the car, and my pregnant sister incredibly frees herself from the wreckage by kicking out the window.As a female filmmaker, I saw the bitter irony of this event as the camera was now turned on me and my loved ones at our most vulnerable. In her discussion of the male gaze, a culturally sanctioned form of narrational violence against women that is ubiquitous in most mainstream media, Mulvey proposes that women are generally the passive image, trapped by the physical limits of the frame in a permanent state of powerlessness as our identity is reduced to her “to-be-looked-at-ness” (40). For a long period of time, the experience of performing the role of this commodified woman of a weaponised male gaze, along with the threat of annihilation associated with our near-death experience, immobilised my spirit. I felt I belonged “more to the dead than to the living” (Herman 34). When I eventually returned to my creative praxis, I decided to use scriptwriting as both my “mode of reasoning and a mode of representation” (Richardson, Writing Strategies 21), test whether I could work through my feelings of alienation and violation and reclaim my agency. This was a complex and harrowing task because my memories “lack[ed] verbal narrative and context” (Herman 38) and were deeply rooted in my body. Cixous confirms that for women, “writing and voice...are woven together” and “spring from the deepest layers of her psyche” (Moi 112). For many months, I struggled to write. I attempted to block out this violent ordeal and censor my self. I soon learnt, however, that my body could not be silenced and was slow to forget. As I tried to write around this experience, the trauma worked itself deeper inside of me, and my physical symptoms worsened, as did the quality of my writing.In the early version of the screenplay I found myself writing a female-centred film about violence, identity and death, using the fictional narrative to express the numbness I experienced. I wrote the female protagonist with detachment as though she were an object devoid of agency. Sartre claims that we make objects of others and of ourselves in an attempt to control the uncertainty of life and the ever-changing nature of humanity (242). Making something into an object is to deprive it of life (and death); it is our attempt to keep ourselves ‘safe’. While I recognise that the car crash’s reminder of my mortality was no doubt part of the reason why I rendered myself, and the script’s female protagonist, lifeless as agentic beings, I sensed that there were subtler operations of power and control behind my self-objectification and self-censorship, which deeply concerned me. What had influenced this dea(r)th of female agency in my creative imaginings? Why did I write my female character with such a red pen? Why did I seem so compelled to ‘kill’ her? I wanted to investigate my gender construction, the complex relationship between my scriptwriting praxis, and the context within which it is produced to discover whether I could write a different future for myself, and my female characters. Kiesinger supports “contextualizing our stories within the framework of a larger picture” (108), so as to remain open to the possibility that there might not be anything ‘wrong’ with us, per se, “but rather something very wrong with the dynamics that dominate the communicative system” (109) within which we operate: in the case of my creative praxis, the oppressive structures present in the culture of film and its pedagogy.Pulling FocusWomen are supposed to be the view and when the view talks back, it is uncomfortable.— Jane Campion (Filming Desire)It is a terrible thing to see that no one has ever taught us how to develop our vision as women neither in the history of arts nor in film schools.— Marie Mandy (Filming Desire)The democratisation of today’s media landscape through new technologies, the recent rise in female-run production companies (Zemler) in Hollywood, along with the ground-breaking #MeToo and Time’s Up movements has elevated the global consciousness of gender-based violence, and has seen the screen industry seek to redress its history of gender imbalance. While it is too early to assess the impact these developments may have on women’s standing in film, today the ‘celluloid ceiling’ still operates on multiple levels of indoctrination and control through a systemic pattern of exclusion for women that upholds the “nearly seamless dialogue among men in cinema” (Lauzen, Thumbs Down 2). Female filmmakers occupy a tenuous position of influence in the mainstream industry and things are not any better on the other side of the camera (Lauzen, The Celluloid Ceiling). For the most part, Hollywood’s male gaze and penchant for sexualising and (physically or figuratively) killing female characters, which normalises violence against women and is “almost inversely proportional to the liberation of women in society” (Mandy), continues to limit women to performing as the image rather than the agent on screen.Film funding bodies and censorship boards, mostly comprised of men, remain exceptionally averse to independent female filmmakers who go against the odds to tell their stories, which often violate taboos about femininity and radically redefine female agency through the construction of the female gaze: a narrational technique of resistance that enables reel woman to govern the point of view, imagery and action of the film (Smelik 51-52). This generally sees their films unjustly ghettoised through incongruent classification or censorship, and forced into independent or underground distribution (Sexton-Finck 165-182). Not only does censorship propose the idea that female agency is abject and dangerous and needs to be restrained, it prevents access to this important cinema by women that aims to counter the male gaze and “shield us from this type of violence” (Gillain 210). This form of ideological and institutional gatekeeping is not only enforced in the film industry, it is also insidiously (re)constituted in the epistemological construction of film discourse and pedagogy, which in their design, are still largely intrinsically gendered institutions, encoded with phallocentric signification that rejects a woman’s specificity and approach to knowledge. Drawing on my mutually informative roles as a former film student and experienced screen educator, I assert that most screen curricula in Australia still uphold entrenched androcentric norms that assume the male gaze and advocate popular cinema’s didactic three-act structure, which conditions our value systems to favour masculinity and men’s worldview. This restorative storytelling approach is argued to be fatally limiting to reel women (Smith 136; Dancyger and Rush 25) as it propagates the Enlightenment notion of a universal subjectivity, based on free will and reason, which neutralises the power structures of society (and film) and repudiates the influence of social positioning on our opportunity for agency. Moreover, through its omniscient consciousness, which seeks to efface the presence of a specific narrator, the three-act method disavows this policing of female agency and absolves any specific individual of responsibility for its structural violence (Dyer 98).By pulling focus on some of these problematic mechanisms in the hostile climate of the film industry and its spaces of learning for women, I became acutely aware of the more latent forms of violence that had conditioned my scriptwriting praxis, the ambivalence I felt towards my female identity, and my consequent gagging of the female character in the screenplay.Changing Lenses How do the specific circumstances in which we write affect what we write? How does what we write affect who we become?— Laurel Richardson (Fields of Play 1)In the beginning, there is an end. Don’t be afraid: it’s your death that is dying. Then: all the beginnings.— Helene Cixous (Cixous and Jensen 41)The discoveries I made during my process of CAP ethnography saw a strong feeling of dissidence arrive inside me. I vehemently wanted to write my way out of my subjugated state and release some of the anguish that my traumatised body was carrying around. I was drawn to militant feminist cinema and the French poststructuralist approach of ‘writing the body’ (l’ecriture feminine) given these deconstructive practices “create images and ideas that have the power to inspire to revolt against oppression and exploitation” (Moi 120). Feminist cinema’s visual treatise of writing the body through its departure from androcentric codes - its unformulaic approach to structure, plot, character and narration (De Lauretis 106) - revealed to me ways in which I could use the scriptwriting process to validate my debilitating experience of physical and psychic violence, decensor my self and move towards rejoining the living. Cixous affirms that, “by writing her self, woman will return to the body which has been more than confiscated from her, which has been turned into…the ailing or dead figure” (Cixous, The Laugh of the Medusa 880). It became clear to me that the persistent themes of death that manifested in the first draft of the script were not, as I first suspected, me ‘rehearsing to die’, or wanting to kill off the woman inside me. I was in fact “not driven towards death but by death” (Homer 89), the close proximity to my mortality, acting as a limit, was calling for a strengthening of my life force, a rebirth of my agency (Bettelheim 36). Mansfield acknowledges that death “offers us a freedom outside of the repression and logic that dominate our daily practices of keeping ourselves in order, within the lines” (87).I challenged myself to write the uncomfortable, the unfamiliar, the unexplored and to allow myself to go to places in me that I had never before let speak by investigating my agency from a much more layered and critical perspective. This was both incredibly terrifying and liberating and enabled me to discard the agentic ‘corset’ I had previously worn in my creative praxis. Dancyger and Rush confirm that “one of the things that happens when we break out of the restorative three-act form is that the effaced narrator becomes increasingly visible and overt” (38). I experienced an invigorating feeling of empowerment through my appropriation of the female gaze in the screenplay which initially appeased some of the post-crash turmoil and general sense of injustice I was experiencing. However, I soon, found something toxic rising inside of me. Like the acrimonious feminist cinema I was immersed in – Raw (Ducournau), A Girl Walks Home at Night (Amirpour), Romance (Breillat), Trouble Every Day (Denis), Baise-Moi (Despentes and Thi), In My Skin (Van), Anatomy of Hell (Breillat) – the screenplay I had produced involved a female character turning the tables on men and using acts of revenge to satisfy her needs. Not only was I creating a highly dystopian world filled with explicit themes of suffering in the screenplay, I too existed in a displaced state of rage and ‘psychic nausea’ in my daily life (Baldick and Sartre). I became haunted by vivid flashbacks of the car crash as abject images, sounds and sensations played over and over in my mind and body like a horror movie on loop. I struggled to find the necessary clarity and counterbalance of stability required to successfully handle this type of experimentation.I do not wish to undermine the creative potential of deconstructive practices, such as writing the body and militant cinema, for female filmmakers. However, I believe my post-trauma sensitivity to visceral entrapment and spiritual violence magnifies some of the psychological and physiological risks involved. Deconstructive experimentation “happens much more easily in the realm of “texts” than in the world of human interaction” (hooks 22) and presents agentic limitations for women since it offers a “utopian vision of female creativity” (Moi 119) that is “devoid of reality...except in a poetic sense” (Moi 122). In jettisoning the restorative qualities of narrative film, new boundaries for women are inadvertently created through restricting us to “intellectual pleasure but rarely emotional pleasure” (Citron 51). Moreover, by reducing women’s agency to retaliation we are denied the opportunity for catharsis and transformation; something I desperately longed to experience in my injured state. Kaplan acknowledges this problem, arguing that female filmmakers need to move theoretically beyond deconstruction to reconstruction, “to manipulate the recognized, dominating discourses so as to begin to free ourselves through rather than beyond them (for what is there ‘beyond’?)” (Women and Film 141).A potent desire to regain a sense of connectedness and control pushed itself out from deep inside me. I yearned for a tonic to move myself and my female character to an active position, rather than a reactive one that merely repeats the victimising dynamic of mainstream film by appropriating a reversed (female) gaze and now makes women the violent victors (Kaplan, Feminism and Film 130). We have arrived at a point where we must destabilise the dominance-submission structure and “think about ways of transcending a polarity that has only brought us all pain” (Kaplan, Feminism and Film 135). I became determined to write a screen narrative that, while dealing with some of the harsh realities of humanity I had become exposed to, involved an existentialist movement towards catharsis and activity.ReframingWhen our stories break down or no longer serve us well, it is imperative that we examine the quality of the stories we are telling and actively reinvent our accounts in ways that permit us to live more fulfilling lives.— Christine Kiesinger (107)I’m frightened by life’s randomness, so I want to deal with it, make some sense of it by telling a film story. But it’s not without hope. I don’t believe in telling stories without some hope.— Susanne Bier (Thomas)Narrative reframing is underlined by the existentialist belief that our spiritual freedom is an artistic process of self-creation, dependent on our free will to organise the elements of our lives, many determined out of our control, into the subjective frame that is to be our experience of our selves and the world around us (107). As a filmmaker, I recognise the power of selective editing and composition. Narrative reframing’s demand for a rational assessment of “the degree to which we live our stories versus the degree to which our stories live us” (Kiesinger 109), helped me to understand how I could use these filmmaking skills to take a step back from my trauma so as to look at it objectively “as a text for study” (Ellis 108) and to exercise power over the creative-destructive forces it, and the deconstructive writing methods I had employed, produced. Richardson confirms the benefits of this practice, since narrative “is the universal way in which humans accommodate to finitude” (Writing Strategies 65).In the script’s development, I found my resilience lay in my capacity to imagine more positive alternatives for female agency. I focussed on writing a narrative that did not avoid life’s hardships and injustices, or require them to be “attenuated, veiled, sweetened, blunted, and falsified” (Nietzsche and Hollingdale 68), yet still involved a life-affirming sentiment. With this in mind, I reintroduced the three-act structure in the revised script as its affectivity and therapeutic denouement enabled me to experience a sense of agentic catharsis that turned “nauseous thoughts into imaginations with which it is possible to live” (Nietzsche 52). Nevertheless, I remained vigilant not to lapse into didacticism; to allow my female character to be free to transgress social conventions surrounding women’s agency. Indebted to Kaplan’s writing on the cinematic gaze, I chose to take up what she identifies as a ‘mutual gaze’; an ethical framework that enabled me to privilege the female character’s perspective and autonomy with a neutral subject-subject gaze rather than the “subject-object kind that reduces one of the parties to the place of submission” (Feminism and Film 135). I incorporated the filmic technique of the point of view (POV) shot for key narrative moments as it allows an audience to literally view the world through a character’s eyes, as well as direct address, which involves the character looking back down the lens at the viewer (us); establishing the highest level of identification between the spectator and the subject on screen.The most pertinent illustration of these significant scriptwriting changes through my engagement with narrative reframing and feminist film theory, is in the reworking of my family’s car crash which became a pivotal turning point in the final draft. In the scene, I use POV and direct address to turn the weaponised gaze back around onto the ‘paparazzi’ who are filming the spectacle. When the central (pregnant) character frees herself from the wreckage, she notices these men filming her and we see the moment from her point of view as she looks at these men laughing and revelling in the commercial potential of their mediatised act. Switching between POV and direct address, the men soon notice they have been exposed as the woman looks back down the lens at them (us) with disbelief, reproaching them (us) for daring to film her in this traumatic moment. She holds her determined gaze while they glance awkwardly back at her, until their laughter dissipates, they stop recording and appear to recognise the culpability of their actions. With these techniques of mutual gazing, I set out to humanise and empower the female victim and neutralise the power dynamic: the woman is now also a viewing agent, and the men equally perform the role of the viewed. In this creative reframing, I hope to provide an antidote to filmic violence against and/or by women as this female character reclaims her (my) experience of survival without adhering to the culture of female passivity or ressentiment.This article has examined how a serious car crash, being filmed against my will in its aftermath and the attendant damages that prevailed from this experience, catalysed a critical change of direction in my scriptwriting. The victimising event helped me recognise the manifest and latent forms of violence against women that are normalised through everyday ideological and institutional systems in film and prevent us from performing as active agents in our creative praxis. There is a critical need for more inclusive modes of practice – across the film industry, discourse and pedagogy – that are cognisant and respectful of women’s specificity and our difference to the androcentric landscape of mainstream film. We need to continue to exert pressure on changing violent mechanisms that marginalise us and ghettoise our stories. As this article has demonstrated, working outside dominant forms can enable important emancipatory opportunities for women, however, this type or deconstruction also presents risks that generally leave us powerless in everyday spaces. While I advocate that female filmmakers should look to techniques of feminist cinema for an alternative lens, we must also work within popular film to critique and subvert it, and not deny women the pleasures and political advantages of its restorative structure. By enabling female filmmakers to (re)humanise woman though encouraging empathy and compassion, this affective storytelling form has the potential to counter violence against women and mobilise female agency. Equally, CAP ethnography and narrative reframing are critical discourses for the retrieval and actualisation of female filmmakers’ agency as they allow us to contextualise our stories of resistance and survival within the framework of a larger picture of violence to gain perspective on our subjective experiences and render them as significant, informative and useful to the lives of others. This enables us to move from the isolated margins of subcultural film and discourse to reclaim our stories at the centre.ReferencesA Girl Walks Home at Night. Dir. Ana Lily Amirpour. Say Ahh Productions, 2014.Anatomy of Hell. Dir. Catherine Breillat. Tartan Films, 2004. Baise-Moi. Dirs. Virginie Despentes and Coralie Trinh Thi. FilmFixx, 2000.Baldick, Robert, and Jean-Paul Sartre. Nausea. 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Bochner and Carolyn Ellis. Walnut Creek, CA: AltaMira Press, 2002. 107-111.Lauzen, Martha M. “Thumbs Down - Representation of Women Film Critics in the Top 100 U.S. Daily Newspapers - A Study by Dr. Martha Lauzen.” Alliance of Women Film Journalists, 25 July 2012. 4-5.———. The Celluloid Ceiling: Behind-the-Scenes Employment of Women on the Top 100, 250, and 500 Films of 2018. Center for the Study of Women in Television and Film San Diego State University 2019. <https://womenintvfilm.sdsu.edu/wp-content/uploads/2019/01/2018_Celluloid_Ceiling_Report.pdf>.Mansfield, Nick. Subjectivity: Theories of the Self from Freud to Haraway. St Leonards, NSW: Allen & Unwin, 2000.Moi, Toril. Sexual/Textual Politics: Feminist Literary Theory. London: Methuen, 2002.Mulvey, Laura. Visual Pleasure and Narrative Cinema in Feminism and Film. Ed. E. Ann Kaplan. New York: Oxford University Press, 1975. 34-47.Nietzsche, Friedrich W. The Birth of Tragedy and the Genealogy of Morals. Trans. Francis Golffing. 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I first came across etoy in Linz, Austria in 1995. They turned up at Ars Electronica with their shaved heads, in their matching orange bomber jackets. They were not invited. The next year they would not have to crash the party. In 1996 they were awarded Arts Electronica’s prestigious Golden Nica for web art, and were on their way to fame and bitterness – the just rewards for their art of self-regard. As founding member Agent.ZAI says: “All of us were extremely greedy – for excitement, for drugs, for success.” (Wishart & Boschler: 16) The etoy story starts on the fringes of the squatters’ movement in Zurich. Disenchanted with the hard left rhetorics that permeate the movement in the 1980s, a small group look for another way of existing within a commodified world, without the fantasy of an ‘outside’ from which to critique it. What Antonio Negri and friends call the ‘real subsumption’ of life under the rule of commodification is something etoy grasps intuitively. The group would draw on a number of sources: David Bowie, the Sex Pistols, the Manchester rave scene, European Amiga art, rumors of the historic avant gardes from Dada to Fluxus. They came together in 1994, at a meeting in the Swiss resort town of Weggis on Lake Lucerne. While the staging of the founding meeting looks like a rerun of the origins of the Situationist International, the wording of the invitation might suggest the founding of a pop music boy band: “fun, money and the new world?” One of the – many – stories about the origins of the name Dada has it being chosen at random from a bilingual dictionary. The name etoy, in an update on that procedure, was spat out by a computer program designed to make four letter words at random. Ironically, both Dada and etoy, so casually chosen, would inspire furious struggles over the ownership of these chancey 4-bit words. The group decided to make money by servicing the growing rave scene. Being based in Vienna and Zurich, the group needed a way to communicate, and chose to use the internet. This was a far from obvious thing to do in 1994. Connections were slow and unreliable. Sometimes it was easier to tape a hard drive full of clubland graphics to the underside of a seat on the express train from Zurich to Vienna and simply email instructions to meet the train and retrieve it. The web was a primitive instrument in 1995 when etoy built its first website. They launched it with a party called etoy.FASTLANE, an optimistic title when the web was anything but. Coco, a transsexual model and tabloid sensation, sang a Japanese song while suspended in the air. She brought media interest, and was anointed etoy’s lifestyle angel. As Wishart and Bochsler write, “it was as if the Seven Dwarfs had discovered their Snow White.” (Wishart & Boschler: 33) The launch didn’t lead to much in the way of a music deal or television exposure. The old media were not so keen to validate the etoy dream of lifting themselves into fame and fortune by their bootstraps. And so etoy decided to be stars of the new media. The slogan was suitably revised: “etoy: the pop star is the pilot is the coder is the designer is the architect is the manager is the system is etoy.” (Wishart & Boschler: 34) The etoy boys were more than net.artists, they were artists of the brand. The brand was achieving a new prominence in the mid-90s. (Klein: 35) This was a time when capitalism was hollowing itself out in the overdeveloped world, shedding parts of its manufacturing base. Control of the circuits of commodification would rest less on the ownership of the means of production and more on maintaining a monopoly on the flows of information. The leading edge of the ruling class was becoming self-consciously vectoral. It controlled the flow of information about what to produce – the details of design, the underlying patents. It controlled the flows of information about what is produced – the brands and logos, the slogans and images. The capitalist class is supplanted by a vectoral class, controlling the commodity circuit through the vectors of information. (Wark) The genius of etoy was to grasp the aesthetic dimension of this new stage of commodification. The etoy boys styled themselves not so much as a parody of corporate branding and management groupthink, but as logical extension of it. They adopted matching uniforms and called themselves agents. In the dada-punk-hiphop tradition, they launched themselves on the world as brand new, self-created, self-named subjects: Agents Zai, Brainhard, Gramazio, Kubli, Esposto, Udatny and Goldstein. The etoy.com website was registered in 1995 with Network Solutions for a $100 fee. The homepage for this etoy.TANKSYSTEM was designed like a flow chart. As Gramazio says: “We wanted to create an environment with surreal content, to build a parallel world and put the content of this world into tanks.” (Wishart & Boschler: 51) One tank was a cybermotel, with Coco the first guest. Another tank showed you your IP number, with a big-brother eye looking on. A supermarket tank offered sunglasses and laughing gas for sale, but which may or may not be delivered. The underground tank included hardcore photos of a sensationalist kind. A picture of the Federal Building in Oklamoma City after the bombing was captioned in deadpan post-situ style “such work needs a lot of training.” (Wishart & Boschler: 52) The etoy agents were by now thoroughly invested in the etoy brand and the constellation of images they had built around it, on their website. Their slogan became “etoy: leaving reality behind.” (Wishart & Boschler: 53) They were not the first artists fascinated by commodification. It was Warhol who said “good art is good business.”(Warhol ) But etoy reversed the equation: good business is good art. And good business, in this vectoral age, is in its most desirable form an essentially conceptual matter of creating a brand at the center of a constellation of signifiers. Late in 1995, etoy held another group meeting, at the Zurich youth center Dynamo. The problem was that while they had build a hardcore website, nobody was visiting it. Agents Gooldstein and Udatny thought that there might be a way of using the new search engines to steer visitors to the site. Zai and Brainhard helped secure a place at the Vienna Academy of Applied Arts where Udatny could use the computer lab to implement this idea. Udatny’s first step was to create a program that would go out and gather email addresses from the web. These addresses would form the lists for the early examples of art-spam that etoy would perpetrate. Udatny’s second idea was a bit more interesting. He worked out how to get the etoy.TANKSYSTEM page listed in search engines. Most search engines ranked pages by the frequency of the search term in the pages it had indexed, so etoy.TANKSYSTEM would contain pages of selected keywords. Porn sites were also discovering this method of creating free publicity. The difference was that etoy chose a very carefully curated list of 350 search terms, including: art, bondage, cyberspace, Doom, Elvis, Fidel, genx, heroin, internet, jungle and Kant. Users of search engines who searched for these terms would find dummy pages listed prominently in their search results that directed them, unsuspectingly, to etoy.com. They called this project Digital Hijack. To give the project a slightly political aura, the pages the user was directed to contained an appeal for the release of convicted hacker Kevin Mitnick. This was the project that won them a Golden Nica statuette at Ars Electronica in 1996, which Gramazio allegedly lost the same night playing roulette. It would also, briefly, require that they explain themselves to the police. Digital Hijack also led to the first splits in the group, under the intense pressure of organizing it on a notionally collective basis, but with the zealous Agent Zai acting as de facto leader. When Udatny was expelled, Zai and Brainhard even repossessed his Toshiba laptop, bought with etoy funds. As Udatny recalls, “It was the lowest point in my life ever. There was nothing left; I could not rely on etoy any more. I did not even have clothes, apart from the etoy uniform.” (Wishart & Boschler: 104) Here the etoy story repeats a common theme from the history of the avant gardes as forms of collective subjectivity. After Digital Hijack, etoy went into a bit of a slump. It’s something of a problem for a group so dependent on recognition from the other of the media, that without a buzz around them, etoy would tend to collapse in on itself like a fading supernova. Zai spend the early part of 1997 working up a series of management documents, in which he appeared as the group’s managing director. Zai employed the current management theory rhetoric of employee ‘empowerment’ while centralizing control. Like any other corporate-Trotskyite, his line was that “We have to get used to reworking the company structure constantly.” (Wishart & Boschler: 132) The plan was for each member of etoy to register the etoy trademark in a different territory, linking identity to information via ownership. As Zai wrote “If another company uses our name in a grand way, I’ll probably shoot myself. And that would not be cool.” (Wishart & Boschler:: 132) As it turned out, another company was interested – the company that would become eToys.com. Zai received an email offering “a reasonable sum” for the etoy.com domain name. Zai was not amused. “Damned Americans, they think they can take our hunting grounds for a handful of glass pearls….”. (Wishart & Boschler: 133) On an invitation from Suzy Meszoly of C3, the etoy boys traveled to Budapest to work on “protected by etoy”, a work exploring internet security. They spent most of their time – and C3’s grant money – producing a glossy corporate brochure. The folder sported a blurb from Bjork: “etoy: immature priests from another world” – which was of course completely fabricated. When Artothek, the official art collection of the Austrian Chancellor, approached etoy wanting to buy work, the group had to confront the problem of how to actually turn their brand into a product. The idea was always that the brand was the product, but this doesn’t quite resolve the question of how to produce the kind of unique artifacts that the art world requires. Certainly the old Conceptual Art strategy of selling ‘documentation’ would not do. The solution was as brilliant as it was simple – to sell etoy shares. The ‘works’ would be ‘share certificates’ – unique objects, whose only value, on the face of it, would be that they referred back to the value of the brand. The inspiration, according to Wishart & Boschsler, was David Bowie, ‘the man who sold the world’, who had announced the first rock and roll bond on the London financial markets, backed by future earnings of his back catalogue and publishing rights. Gramazio would end up presenting Chancellor Viktor Klima with the first ‘shares’ at a press conference. “It was a great start for the project”, he said, “A real hack.” (Wishart & Boschler: 142) For this vectoral age, etoy would create the perfect vectoral art. Zai and Brainhard took off next for Pasadena, where they got the idea of reverse-engineering the online etoy.TANKSYSTEM by building an actual tank in an orange shipping container, which would become etoy.TANK 17. This premiered at the San Francisco gallery Blasthaus in June 1998. Instant stars in the small world of San Francisco art, the group began once again to disintegrate. Brainhard and Esposito resigned. Back in Europe in late 1998, Zai was preparing to graduate from the Vienna Academy of Applied Arts. His final project would recapitulate the life and death of etoy. It would exist from here on only as an online archive, a digital mausoleum. As Kubli says “there was no possibility to earn our living with etoy.” (Wishart & Boschler: 192) Zai emailed eToys.com and asked them if them if they would like to place a banner ad on etoy.com, to redirect any errant web traffic. Lawyers for eToys.com offered etoy $30,000 for the etoy.com domain name, which the remaining members of etoy – Zai, Gramazio, Kubli – refused. The offer went up to $100,000, which they also refused. Through their lawyer Peter Wild they demanded $750,000. In September 1999, while etoy were making a business presentation as their contribution to Ars Electronica, eToys.com lodged a complaint against etoy in the Los Angeles Superior Court. The company hired Bruce Wessel, of the heavyweight LA law firm Irell & Manella, who specialized in trademark, copyright and other intellectual property litigation. The complaint Wessel drafted alleged that etoy had infringed and diluted the eToys trademark, were practicing unfair competition and had committed “intentional interference with prospective economic damage.” (Wishart & Boschler: 199) Wessel demanded an injunction that would oblige etoy to cease using its trademark and take down its etoy.com website. The complaint also sought to prevent etoy from selling shares, and demanded punitive damages. Displaying the aggressive lawyering for which he was so handsomely paid, Wessel invoked the California Unfair Competition Act, which was meant to protect citizens from fraudulent business scams. Meant as a piece of consumer protection legislation, its sweeping scope made it available for inventive suits such as Wessel’s against etoy. Wessel was able to use pretty much everything from the archive etoy built against it. As Wishart and Bochsler write, “The court papers were like a delicately curated catalogue of its practices.” (Wishart & Boschler: 199) And indeed, legal documents in copyright and trademark cases may be the most perfect literature of the vectoral age. The Unfair Competition claim was probably aimed at getting the suit heard in a Californian rather than a Federal court in which intellectual property issues were less frequently litigated. The central aim of the eToys suit was the trademark infringement, but on that head their claims were not all that strong. According to the 1946 Lanham Act, similar trademarks do not infringe upon each other if there they are for different kinds of business or in different geographical areas. The Act also says that the right to own a trademark depends on its use. So while etoy had not registered their trademark and eToys had, etoy were actually up and running before eToys, and could base their trademark claim on this fact. The eToys case rested on a somewhat selective reading of the facts. Wessel claimed that etoy was not using its trademark in the US when eToys was registered in 1997. Wessel did not dispute the fact that etoy existed in Europe prior to that time. He asserted that owning the etoy.com domain name was not sufficient to establish a right to the trademark. If the intention of the suit was to bully etoy into giving in, it had quite the opposite effect. It pissed them off. “They felt again like the teenage punks they had once been”, as Wishart & Bochsler put it. Their art imploded in on itself for lack of attention, but called upon by another, it flourished. Wessel and eToys.com unintentionally triggered a dialectic that worked in quite the opposite way to what they intended. The more pressure they put on etoy, the more valued – and valuable – they felt etoy to be. Conceptual business, like conceptual art, is about nothing but the management of signs within the constraints of given institutional forms of market. That this conflict was about nothing made it a conflict about everything. It was a perfectly vectoral struggle. Zai and Gramazio flew to the US to fire up enthusiasm for their cause. They asked Wolfgang Staehle of The Thing to register the domain toywar.com, as a space for anti-eToys activities at some remove from etoy.com, and as a safe haven should eToys prevail with their injunction in having etoy.com taken down. The etoy defense was handled by Marcia Ballard in New York and Robert Freimuth in Los Angeles. In their defense, they argued that etoy had existed since 1994, had registered its globally accessible domain in 1995, and won an international art prize in 1996. To counter a claim by eToys that they had a prior trademark claim because they had bought a trademark from another company that went back to 1990, Ballard and Freimuth argued that this particular trademark only applied to the importation of toys from the previous owner’s New York base and thus had no relevance. They capped their argument by charging that eToys had not shown that its customers were really confused by the existence of etoy. With Christmas looming, eToys wanted a quick settlement, so they offered Zurich-based etoy lawyer Peter Wild $160,000 in shares and cash for the etoy domain. Kubli was prepared to negotiate, but Zai and Gramazio wanted to gamble – and raise the stakes. As Zai recalls: “We did not want to be just the victims; that would have been cheap. We wanted to be giants too.” (Wishart & Boschler: 207) They refused the offer. The case was heard in November 1999 before Judge Rafeedie in the Federal Court. Freimuth, for etoy, argued that federal Court was the right place for what was essentially a trademark matter. Robert Kleiger, for eToys, countered that it should stay where it was because of the claims under the California Unfair Competition act. Judge Rafeedie took little time in agreeing with the eToys lawyer. Wessel’s strategy paid off and eToys won the first skirmish. The first round of a quite different kind of conflict opened when etoy sent out their first ‘toywar’ mass mailing, drawing the attention of the net.art, activism and theory crowd to these events. This drew a report from Felix Stalder in Telepolis: “Fences are going up everywhere, molding what once seemed infinite space into an overcrowded and tightly controlled strip mall.” (Stalder ) The positive feedback from the net only emboldened etoy. For the Los Angeles court, lawyers for etoy filed papers arguing that the sale of ‘shares’ in etoy was not really a stock offering. “The etoy.com website is not about commerce per se, it is about artist and social protest”, they argued. (Wishart & Boschler: 209) They were obliged, in other words, to assert a difference that the art itself had intended to blur in order to escape eToy’s claims under the Unfair Competition Act. Moreover, etoy argued that there was no evidence of a victim. Nobody was claiming to have been fooled by etoy into buying something under false pretences. Ironically enough, art would turn out in hindsight to be a more straightforward transaction here, involving less simulation or dissimulation, than investing in a dot.com. Perhaps we have reached the age when art makes more, not less, claim than business to the rhetorical figure of ‘reality’. Having defended what appeared to be the vulnerable point under the Unfair Competition law, etoy went on the attack. It was the failure of eToys to do a proper search for other trademarks that created the problem in the first place. Meanwhile, in Federal Court, lawyers for etoy launched a counter-suit that reversed the claims against them made by eToys on the trademark question. While the suits and counter suits flew, eToys.com upped their offer to settle to a package of cash and shares worth $400,000. This rather puzzled the etoy lawyers. Those choosing to sue don’t usually try at the same time to settle. Lawyer Peter Wild advised his clients to take the money, but the parallel tactics of eToys.com only encouraged them to dig in their heels. “We felt that this was a tremendous final project for etoy”, says Gramazio. As Zai says, “eToys was our ideal enemy – we were its worst enemy.” (Wishart & Boschler: 210) Zai reported the offer to the net in another mass mail. Most people advised them to take the money, including Doug Rushkoff and Heath Bunting. Paul Garrin counseled fighting on. The etoy agents offered to settle for $750,000. The case came to court in late November 1999 before Judge Shook. The Judge accepted the plausibility of the eToys version of the facts on the trademark issue, which included the purchase of a registered trademark from another company that went back to 1990. He issued an injunction on their behalf, and added in his statement that he was worried about “the great danger of children being exposed to profane and hardcore pornographic issues on the computer.” (Wishart & Boschler: 222) The injunction was all eToys needed to get Network Solutions to shut down the etoy.com domain. Zai sent out a press release in early December, which percolated through Slashdot, rhizome, nettime (Staehle) and many other networks, and catalyzed the net community into action. A debate of sorts started on investor websites such as fool.com. The eToys stock price started to slide, and etoy ‘warriors’ felt free to take the credit for it. The story made the New York Times on 9th December, Washington Post on the 10th, Wired News on the 11th. Network Solutions finally removed the etoy.com domain on the 10th December. Zai responded with a press release: “this is robbery of digital territory, American imperialism, corporate destruction and bulldozing in the way of the 19th century.” (Wishart & Boschler: 237) RTMark set up a campaign fund for toywar, managed by Survival Research Laboratories’ Mark Pauline. The RTMark press release promised a “new internet ‘game’ designed to destroy eToys.com.” (Wishart & Boschler: 239) The RTMark press release grabbed the attention of the Associated Press newswire. The eToys.com share price actually rose on December 13th. Goldman Sachs’ e-commerce analyst Anthony Noto argued that the previous declines in the Etoys share price made it a good buy. Goldman Sachs was the lead underwriter of the eToys IPO. Noto’s writings may have been nothing more than the usual ‘IPOetry’ of the time, but the crash of the internet bubble was some months away yet. The RTMark campaign was called ‘The Twelve Days of Christmas’. It used the Floodnet technique that Ricardo Dominguez used in support of the Zapatistas. As Dominguez said, “this hysterical power-play perfectly demonstrates the intensions of the new net elite; to turn the World Wide Web into their own private home-shopping network.” (Wishart & Boschler: 242) The Floodnet attack may have slowed the eToys.com server down a bit, but it was robust and didn’t crash. Ironically, it ran on open source software. Dominguez claims that the ‘Twelve Days’ campaign, which relied on individuals manually launching Floodnet from their own computers, was not designed to destroy the eToys site, but to make a protest felt. “We had a single-bullet script that could have taken down eToys – a tactical nuke, if you will. But we felt this script did not represent the presence of a global group of people gathered to bear witness to a wrong.” (Wishart & Boschler: 245) While the eToys engineers did what they could to keep the site going, eToys also approached universities and businesses whose systems were being used to host Floodnet attacks. The Thing, which hosted Dominguez’s eToys Floodnet site was taken offline by The Thing’s ISP, Verio. After taking down the Floodnet scripts, The Thing was back up, restoring service to the 200 odd websites that The Thing hosted besides the offending Floodnet site. About 200 people gathered on December 20th at a demonstration against eToys outside the Museum of Modern Art. Among the crowd were Santas bearing signs that said ‘Coal for eToys’. The rally, inside the Museum, was led by the Reverend Billy of the Church of Stop Shopping: “We are drowning in a sea of identical details”, he said. (Wishart & Boschler: 249-250) Meanwhile etoy worked on the Toywar Platform, an online agitpop theater spectacle, in which participants could act as soldiers in the toywar. This would take some time to complete – ironically the dispute threatened to end before this last etoy artwork was ready, giving etoy further incentives to keep the dispute alive. The etoy agents had a new lawyer, Chris Truax, who was attracted to the case by the publicity it was generating. Through Truax, etoy offered to sell the etoy domain and trademark for $3.7 million. This may sound like an insane sum, but to put it in perspective, the business.com site changed hands for $7.5 million around this time. On December 29th, Wessel signaled that eToys was prepared to compromise. The problem was, the Toywar Platform was not quite ready, so etoy did what it could to drag out the negotiations. The site went live just before the scheduled court hearings, January 10th 2000. “TOYWAR.com is a place where all servers and all involved people melt and build a living system. In our eyes it is the best way to express and document what’s going on at the moment: people start to about new ways to fight for their ideas, their lifestyle, contemporary culture and power relations.” (Wishart & Boschler: 263) Meanwhile, in a California courtroom, Truax demanded that Network Solutions restore the etoy domain, that eToys pay the etoy legal expenses, and that the case be dropped without prejudice. No settlement was reached. Negotiations dragged on for another two weeks, with the etoy agents’ attention somewhat divided between two horizons – art and law. The dispute was settled on 25th January. Both parties dismissed their complaints without prejudice. The eToys company would pay the etoy artists $40,000 for legal costs, and contact Network Solutions to reinstate the etoy domain. “It was a pleasure doing business with one of the biggest e-commerce giants in the world” ran the etoy press release. (Wishart & Boschler: 265) That would make a charming end to the story. But what goes around comes around. Brainhard, still pissed off with Zai after leaving the group in San Francisco, filed for the etoy trademark in Austria. After that the internal etoy wranglings just gets boring. But it was fun while it lasted. What etoy grasped intuitively was the nexus between the internet as a cultural space and the transformation of the commodity economy in a yet-more abstract direction – its becoming-vectoral. They zeroed in on the heart of the new era of conceptual business – the brand. As Wittgenstein says of language, what gives words meaning is other words, so too for brands. What gives brands meaning is other brands. There is a syntax for brands as there is for words. What etoy discovered is how to insert a new brand into that syntax. The place of eToys as a brand depended on their business competition with other brands – with Toys ‘R’ Us, for example. For etoy, the syntax they discovered for relating their brand to another one was a legal opposition. What made etoy interesting was their lack of moral posturing. Their abandonment of leftist rhetorics opened them up to exploring the territory where media and business meet, but it also made them vulnerable to being consumed by the very dialectic that created the possibility of staging etoy in the first place. By abandoning obsolete political strategies, they discovered a media tactic, which collapsed for want of a new strategy, for the new vectoral terrain on which we find ourselves. Works Cited Negri, Antonio. Time for Revolution. Continuum, London, 2003. Warhol, Andy. From A to B and Back Again. Picador, New York, 1984. Stalder, Felix. ‘Fences in Cyberspace: Recent events in the battle over domain names’. 19 Jun 2003. <http://felix.openflows.org/html/fences.php>. Wark, McKenzie. ‘A Hacker Manifesto [version 4.0]’ 19 Jun 2003. http://subsol.c3.hu/subsol_2/contributors0/warktext.html. Klein, Naomi. No Logo. Harper Collins, London, 2000. Wishart, Adam & Regula Bochsler. Leaving Reality Behind: etoy vs eToys.com & Other Battles to Control Cyberspace Ecco Books, 2003. Staehle, Wolfgang. ‘<nettime> etoy.com shut down by US court.’ 19 Jun 2003. http://amsterdam.nettime.org/Lists-Archives/nettime-l-9912/msg00005.html Links http://amsterdam.nettime.org/Lists-Archives/nettime-l-9912/msg00005.htm http://felix.openflows.org/html/fences.html http://subsol.c3.hu/subsol_2/contributors0/warktext.html Citation reference for this article Substitute your date of access for Dn Month Year etc... MLA Style Wark, McKenzie. "Toywars" M/C: A Journal of Media and Culture< http://www.media-culture.org.au/0306/02-toywars.php>. APA Style Wark, M. (2003, Jun 19). Toywars. M/C: A Journal of Media and Culture, 6,< http://www.media-culture.org.au/0306/02-toywars.php>