Journal articles on the topic 'Switch probability effects'
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Gluzberg, Boris, Vadim Korolev, Alexey Loktev, Irina Shishkina, and Mikhail Berezovsky. "Switch operation safety." E3S Web of Conferences 138 (2019): 01017. http://dx.doi.org/10.1051/e3sconf/201913801017.
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The article studied the safety of passing the rolling stock by railway switches. On railway switches, counter rails provide the safe passage of the rolling stock by the wheelsets through the harmful space of the cross. The levels of dynamic effects arising from the passage of carriages by the railway switch significantly depend on the relative position of the wheelsets and elements of the switch, which is determined by the combination of their main geometric dimensions. To calculate the most unfavorable combinations of wheelset and gauge dimensions, taking into account the tolerances adopted for these dimensions, the method of probability compositions is used, based on the application of the theory of probability. The calculating apparatus of the approach using conditional probabilities of events based on the formulas of total probability and Bayes formula. The level of impact of the wheels on the counter-rail is regulated by rationing the values of the “impact effect” on the bent and catching parts of the counter-rail.
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Zhan, Zhuozhao, Geertruida H. de Bock, and Edwin R. van den Heuvel. "Statistical methods for unidirectional switch designs: Past, present, and future." Statistical Methods in Medical Research 27, no. 9 (January 26, 2017): 2872–82. http://dx.doi.org/10.1177/0962280216689280.
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Clinical trials may apply or use a sequential introduction of a new treatment to determine its efficacy or effectiveness with respect to a control treatment. The reasons for choosing a particular switch design have different origins. For instance, they may be implemented for ethical or logistic reasons or for studying disease-modifying effects. Large-scale pragmatic trials with complex interventions often use stepped wedge designs (SWDs), where all participants start at the control group, and during the trial, the control treatment is switched to the new intervention at different moments. They typically use cross-sectional data and cluster randomization. On the other hand, new drugs for inhibition of cognitive decline in Alzheimer’s or Parkinson’s disease typically use delayed start designs (DSDs). Here, participants start in a parallel group design and at a certain moment in the trial, (part of) the control group switches to the new treatment. The studies are longitudinal in nature, and individuals are being randomized. Statistical methods for these unidirectional switch designs (USD) are quite complex and incomparable, and they have been developed by various authors under different terminologies, model specifications, and assumptions. This imposes unnecessary barriers for researchers to compare results or choose the most appropriate method for their own needs. This paper provides an overview of past and current statistical developments for the USDs (SWD and DSD). All designs are formulated in a unified framework of treatment patterns to make comparisons between switch designs easier. The focus is primarily on statistical models, methods of estimation, sample size calculation, and optimal designs for estimation of the treatment effect. Other relevant open issues are being discussed as well to provide suggestions for future research in USDs.
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Wu, Songtao, Jianmin He, and Shouwei Li. "Effects of fundamentals acquisition and strategy switch on stock price dynamics." Physica A: Statistical Mechanics and its Applications 491 (February 2018): 799–809. http://dx.doi.org/10.1016/j.physa.2017.09.072.
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Cheng, Weijun, Xiaoting Wang, Tengfei Ma, and Gang Wang. "On the Performance Analysis of Switched Diversity Combining Receivers over Fisher–Snedecor ℱ Composite Fading Channels." Sensors 21, no. 9 (April 25, 2021): 3014. http://dx.doi.org/10.3390/s21093014.
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In some emerging wireless applications, such as wearable communication and low-power sensor network applications, wireless devices or nodes not only require simple physical implementation approaches but also require certain reliable receiver techniques to overcome the effects of multipath or shadowed fading. Switched diversity combining (SDC) systems could be a simple and promising solution to the above requirements. Recently, a Fisher–Snedecor F composited fading model has gained much interest because of its modeling accuracy and calculation tractability. However, the performance of SDC systems over F fading channels has not yet been analyzed in the open literature. To this end, this paper presents a systematic analysis of SDC systems over F fading channels, including dual-branch switch-and-stay combining (SSC), multibranch switch-and examine combining (SEC), and SEC with post-examining selection (SECps) systems. We first investigate the statistical characteristics of univariate and bivariate F distributions. Then, these statistical expressions are introduced into the above SDC systems and the statistical metrics of the output signal-to-noise ratio (SNR) for these systems are deduced in different F fading scenarios. Thirdly, certain exact and novel expressions of performance criteria, such as the outage probability, the average bit error probability and average symbol error probability, as well as the average channel capacity for SSC, SEC, and SECps are derived. To find the optimum performance, optimal analysis is performed for the independent and identically distributed cases. Finally, numerical evaluation and simulations are carried out to demonstrate the validity of the theoretical analysis under various F fading scenarios. According to the obtained results, the multipath fading parameter has more influence on the performance of SDC systems than the shadowing parameter, the correlation coefficient, or the average SNR. Importantly, the SDC systems can provide switched diversity gains only when the switching threshold is not too large or too small compared to the average SNR.
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Pronzato, P., M. E. Cazzaniga, G. Mustacchi, A. De Matteis, F. Di Costanzo, C. Verusio, N. Marzano, E. Rulli, and I. Floriani. "Factors influencing the switch from Tamoxifen (TAM) to Aromatase Inhibitors (AIs) as adjuvant therapy in early breast cancer (EBC) patients (pts). Results from the NORA study." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10633. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10633.
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10633 Background: Results from recent trials indicate that AIs as adjuvant treatment, either as up-front therapy or sequencing after TAM, can improve the clinical outcome of EBC pts. It is therefore important to assess the prevalence of the AI use in adjuvant setting and the reasons associated to the choice of this treatment. PATIENTS AND Methods: The NORA trial is an observational study, aimed at investigating adjuvant treatment modalities, that consecutively enrolled 3515 EBC pts, according to the following criteria: 10 pts each year starting from 2000 (retrospective cohort) and 20 pts starting from the beginning of 2003 or the date of ethical approval, if subsequent (prospective cohort). Using data from NORA, we focused on the subgroup of pts who switched from TAM to AIs in order to determine which factors are more likely to be associated with the probability of switching. Multivariate analysis was conducted using the Cox’s regression model. Results: Out of 2075 pts who started TAM, 329 (15.9%) switched to AIs. They had a median age of 63.1 yrs, 147 (45.9%) were N+, 190 (57.8%) received chemotherapy, 179 (54.6%) were T1, 248 (77.5%) were ER+/PgR+. Switch from TAM to AIs was influenced by N+ status, previous chemotherapy and age, whereas no effect was observed for T size or HR status. Previous chemotherapy increases the probability of switching by 27% (95% CI -4% to +70%, p = 0.10), each age decade increase by 35% (95% CI +21% to +52%, p < 0.0001), N+ status by 16% (95% CI +1% to 34%, p = 0.03). Conclusion: As expected, high risk N+ pts have higher probabilities to be switched in comparison to other groups, probably due to the encouraging results of AIs trials. In previously treated or older age pts, TAM side effects could have determined the switch. No significant financial relationships to disclose.
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Latimer, NR, IR White, K. Tilling, and U. Siebert. "Improved two-stage estimation to adjust for treatment switching in randomised trials: g-estimation to address time-dependent confounding." Statistical Methods in Medical Research 29, no. 10 (March 30, 2020): 2900–2918. http://dx.doi.org/10.1177/0962280220912524.
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In oncology trials, control group patients often switch onto the experimental treatment during follow-up, usually after disease progression. In this case, an intention-to-treat analysis will not address the policy question of interest – that of whether the new treatment represents an effective and cost-effective use of health care resources, compared to the standard treatment. Rank preserving structural failure time models (RPSFTM), inverse probability of censoring weights (IPCW) and two-stage estimation (TSE) have often been used to adjust for switching to inform treatment reimbursement policy decisions. TSE has been applied using a simple approach (TSEsimp), assuming no time-dependent confounding between the time of disease progression and the time of switch. This is problematic if there is a delay between progression and switch. In this paper we introduce TSEgest, which uses structural nested models and g-estimation to account for time-dependent confounding, and compare it to TSEsimp, RPSFTM and IPCW. We simulated scenarios where control group patients could switch onto the experimental treatment with and without time-dependent confounding being present. We varied switching proportions, treatment effects and censoring proportions. We assessed adjustment methods according to their estimation of control group restricted mean survival times that would have been observed in the absence of switching. All methods performed well in scenarios with no time-dependent confounding. TSEgest and RPSFTM continued to perform well in scenarios with time-dependent confounding, but TSEsimp resulted in substantial bias. IPCW also performed well in scenarios with time-dependent confounding, except when inverse probability weights were high in relation to the size of the group being subjected to weighting, which occurred when there was a combination of modest sample size and high switching proportions. TSEgest represents a useful addition to the collection of methods that may be used to adjust for treatment switching in trials in order to address policy-relevant questions.
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WANG, CAN-JUN. "DELAYS INDUCE DIFFERENT SWITCH IN A STOCHASTIC SINGLE GENETIC REGULATION SYSTEM WITH A POSITIVE AUTOREGULATORY FEEDBACK LOOP." International Journal of Modern Physics B 27, no. 11 (April 25, 2013): 1350085. http://dx.doi.org/10.1142/s0217979213500859.
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The steady properties of a stochastic single genetic regulation system with the different time delays, which appear in the deterministic and fluctuating forces, are investigated based on the small delay time approximation method. Using the approximation probability density approach, the delayed Fokker–Planck equation is obtained. The effects of two different time delays on the stationary probability distribution and the mean value are discussed. It is found that with the time delay τ1 in the deterministic force increasing, the TF-A monomer concentration shifts from "off" state to "on" state. However, with the time delay τ2 in the fluctuating force increasing, the TF-A monomer concentration shifts from "on" state to "off" state. In the switch process, two kinds of time delays play an opposite role. The theoretical predictions are found to be in good agreement with numerical results.
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Huang, Tao, Qian Gu, Zhangyan Deng, Chilun Tsai, Yue Xue, Jimeng Zhang, Liye Zou, Zuosong Chen, and Kun Wang. "Executive Function Performance in Young Adults When Cycling at an Active Workstation: An fNIRS Study." International Journal of Environmental Research and Public Health 16, no. 7 (March 28, 2019): 1119. http://dx.doi.org/10.3390/ijerph16071119.
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Background: This study aimed to investigate the effects of self-paced cycling at an active workstation on executive functions and cortical activity. Methods: In a crossover study design, 37 young adults (45.9% females) were randomly assigned to the following two task conditions: (1) performing cognitive tests during sitting, (2) performing cognitive tests while cycling at an active workstation. Executive functions were assessed by the Stroop color and word test and the task-switching paradigm. Cortical activity was monitored using a multi-channel functional near-infrared spectroscopy (fNIRS) system. Results: The behavioral results showed that there were no significant differences on the Stroop interference effects (P = 0.66) between the sitting and the cycling conditions. In all probability, no differences on the global switch costs (P = 0.90) and local switch costs (P = 0.67) were observed between the sitting and the cycling conditions. For the fNIRS results, the oxygenated hemoglobin (oxy-Hb) in response to the Stroop interference in channels 5, 10, and 12 were decreased during the cycling condition (all Ps < 0.05, FDR-corrected). Conversely, the oxy-Hb associated with the global switch costs in channels 3, 29, and 31 were increased during the cycling condition (all Ps < 0.05, FDR-corrected). Conclusions: The findings indicated that behavioral performances on executive functions were not affected by cycling at an active workstation, while cognitive resources were reallocated during cycling at an active workstation.
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Jenkins, Jade Marcus, Terri J. Sabol, and George Farkas. "Double Down or Switch It Up: Should Low-Income Children Stay in Head Start for 2 Years or Switch Programs?" Evaluation Review 42, no. 3 (June 2018): 283–317. http://dx.doi.org/10.1177/0193841x18786591.
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Background: Recent growth in subsidized preschool opportunities in the United States for low-income 4-year-old children has allowed federal Head Start programs to fund more slots for 3-year-old children. In turn, when Age-3 Head Start participants turn four, they may choose to switch into one of the many alternative care options or choose to stay in Head Start for a second year. Objectives: We analyze a nationally representative sample of Age-3 Head Start participants to examine whether children who stay in Head Start for a second year at Age 4 exhibit greater school readiness and subsequent cognitive and behavioral performance compared with children who switch out of Head Start into alternative care. We also examine differences between children who stay at the same Head Start center at Age 4 with those who switch to a different Head Start center. Research Design: Child fixed effects analyses coupled with inverse probability of treatment weights to remove observable, time-invariant differences between Head Start stayers and switchers. Subjects: Cohort of Age-3 Head Start attendees from the Head Start Impact Study. Measures: Child cognitive and behavioral skills assessed by trained administrators annually at ages 3–7. Results: Age-3 Head Start participants’ outcomes do not differ at the end of preschool, kindergarten, or first grade based on their choice of Age-4 program. Staying at the same Head Start center for 2 years may be beneficial for behavioral skills. Conclusions: For low-income families, there exist many equally beneficial options to support their children’s school readiness through public preschool programs.
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Petkovic, Milica, and Goran Djordjevic. "Performance analysis of coherent FSO system with SSC receiver." Serbian Journal of Electrical Engineering 13, no. 3 (2016): 395–404. http://dx.doi.org/10.2298/sjee1603395p.
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This paper analyzes the performance of coherent free-space optical (FSO) system employing the switch-and-stay (SSC) dual diversity receiver. The intensity fluctuations of the optical signal are modeled by Gamma-Gamma distribution, being caused by atmospheric turbulence. In addition, pointing errors are taken into account. Novel analytical expressions for the outage probability are derived. The general scenario of unbalanced average signal-to-noise ratios (SNRs) of independent and identically distributed SSC branches is considered, which is further simplified to the balanced SNR case. The effects of various system and channel parameters are investigated and discussed.
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Terebus, Anna, and Jie Liang. "Effects of Gene Duplication on the Non-Equilibrium Dynamics of Probability Mass in Toggle-Switch: Cellular States, Sources and Sinks, Oscillations." Biophysical Journal 114, no. 3 (February 2018): 151a—152a. http://dx.doi.org/10.1016/j.bpj.2017.11.850.
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Currie, Stephen P., Denis Combes, Nicholas W. Scott, John Simmers, and Keith T. Sillar. "A behaviorally related developmental switch in nitrergic modulation of locomotor rhythmogenesis in larval Xenopus tadpoles." Journal of Neurophysiology 115, no. 3 (March 1, 2016): 1446–57. http://dx.doi.org/10.1152/jn.00283.2015.
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Locomotor control requires functional flexibility to support an animal's full behavioral repertoire. This flexibility is partly endowed by neuromodulators, allowing neural networks to generate a range of motor output configurations. In hatchling Xenopus tadpoles, before the onset of free-swimming behavior, the gaseous modulator nitric oxide (NO) inhibits locomotor output, shortening swim episodes and decreasing swim cycle frequency. While populations of nitrergic neurons are already present in the tadpole's brain stem at hatching, neurons positive for the NO-synthetic enzyme, NO synthase, subsequently appear in the spinal cord, suggesting additional as yet unidentified roles for NO during larval development. Here, we first describe the expression of locomotor behavior during the animal's change from an early sessile to a later free-swimming lifestyle and then compare the effects of NO throughout tadpole development. We identify a discrete switch in nitrergic modulation from net inhibition to overall excitation, coincident with the transition to free-swimming locomotion. Additionally, we show in isolated brain stem-spinal cord preparations of older larvae that NO's excitatory effects are manifested as an increase in the probability of spontaneous swim episode occurrence, as found previously for the neurotransmitter dopamine, but that these effects are mediated within the brain stem. Moreover, while the effects of NO and dopamine are similar, the two modulators act in parallel rather than NO operating serially by modulating dopaminergic signaling. Finally, NO's activation of neurons in the brain stem also leads to the release of NO in the spinal cord that subsequently contributes to NO's facilitation of swimming.
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Liu, Xuemei, Wei Chen, William H. Meyers, and Yinguo Dong. "Effects of heterogeneous SPS measures on agricultural growth: Evidence from China." PLOS ONE 17, no. 5 (May 10, 2022): e0266904. http://dx.doi.org/10.1371/journal.pone.0266904.
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In order to explore the sustainable growth of Chinese agriculture, this paper assesses how the heterogeneous SPS measures affect China’s growth margins and quality upgrading in the agricultural sector. We estimate improved gravity-model that exploit the cross-country differences in SPS measures over the period from 2000 to 2014. Our findings show that the heterogeneous SPS measures restrict the intensive margin and extensive margin, but significantly promote the product quality-even with no significant effect on price index. Conditional on quality upgrading, the heterogeneous SPS measures decrease the extent of quality upgrading. On one hand, because of cross-country differences in SPS standards, standards from developed countries have less effective trade effect on China’s agri-products export quality upgrading; On the other hand, because of cross-firm differences in the ability to deal with SPS standards, the laggards in China have the higher probability to switch to lower entrance barrier countries. Therefore, it is possible for China to trap in the low-quality agricultural growth in the long term.
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Saha, Barsha, Miguel Martínez-García, Sharad Nath Bhattacharya, and Rohit Joshi. "Overcoming Choice Inertia through Social Interaction—An Agent-Based Study of Mobile Subscription Decision." Games 13, no. 3 (June 20, 2022): 47. http://dx.doi.org/10.3390/g13030047.
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Subscription decision in the telecom market is quite complex and cumbersome, invoking decision inertia in consumers and resulting in suboptimal choices. We implemented choice inertia and consumer interaction as an agent-based model to better understand the process. The model illustrates that with adequate peer interactions with active consumers, inactive consumers could overcome their inertia significantly and switch to a better alternative. Furthermore, the newly converted active consumers influenced their inert neighbors as a ripple effect. Active consumers contribute to firm profits and healthy market competition. Moreover, in environments with low neighborhood effects and a stronger inertia threshold, firms are able to maintain profits by retaining inert consumers. We show that apart from the attractiveness of market offerings, firms can benefit from understanding consumer inertia and devising means to reduce it.
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Luo, L., I. Reimert, E. A. M. Graat, S. Smeets, B. Kemp, and J. E. Bolhuis. "Effects of early life and current housing on sensitivity to reward loss in a successive negative contrast test in pigs." Animal Cognition 23, no. 1 (November 13, 2019): 121–30. http://dx.doi.org/10.1007/s10071-019-01322-w.
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Abstract Animals in a negative affective state seem to be more sensitive to reward loss, i.e. an unexpected decrease in reward size. The aim of this study was to investigate whether early-life and current enriched vs. barren housing conditions affect the sensitivity to reward loss in pigs using a successive negative contrast test. Pigs (n = 64 from 32 pens) were housed in barren or enriched conditions from birth onwards, and at 7 weeks of age experienced either a switch in housing conditions (from barren to enriched or vice versa) or not. Allotting pigs to the different treatments was balanced for coping style (proactive vs. reactive). One pig per pen was trained to run for a large reward and one for a small reward. Reward loss was introduced for pigs receiving the large reward after 11 days (reward downshift), i.e. from then onwards, they received the small reward. Pigs housed in barren conditions throughout life generally had a lower probability and higher latency to get the reward than other pigs. Proactive pigs ran overall slower than reactive pigs. After the reward downshift, all pigs ran slower. Nevertheless, reward downshift increased the latency and reduced the probability to get to the reward, but only in pigs exposed to barren conditions in early life, which thus were more sensitive to reward loss than pigs from enriched early life housing. In conclusion, barren housed pigs seemed overall less motivated for the reward, and early life housing conditions had long-term effects on the sensitivity to reward loss.
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Ojeda Silva, Judith Helena, Juan Sebastián Paez Barbosa, and Carlos Alberto Duque Echeverri. "Thermo-Electrical Conduction of the 2,7-Di([1,1′-Biphenyl]-4-yl)-9H-Fluorene Molecular System: Coupling between Benzene Rings and Stereoelectronic Effects." Molecules 25, no. 14 (July 14, 2020): 3215. http://dx.doi.org/10.3390/molecules25143215.
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Theoretical and analytical thermal and electrical properties are studied through the 2,7-Di([1,1′-biphenyl]-4-yl)-9H-fluorene aromatic system as a prototype of a molecular switch. Variations of the dihedral angles between the two Benzene rings at each end of the molecule have been considered, thus determining the dependence on the structural variation of the molecule when the aromatic system is connected between metal contacts. The molecule is modeled through a Tight-Binding Hamiltonian where—from the analytical process of decimation and using Green’s functions—the probability of transmission (T) is calculated by using the Fisher–Lee relationship. Consequently, the thermal and electrical transport properties such as I − V curves, quantum noise (S), Fano factor (F), electrical conductance (G), thermal conductance ( κ ), Seebeck coefficient (Q), and merit number ( Z T ) are calculated. The available results offer the possibility of designing molecular devices, where the change in conductance or current induced by a stereoelectronic effect on the molecular junctions (within the aromatic system) can produce changes on the insulating–conductive states.
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Zilberberg, Noam, Nitza Ilan, Rosana Gonzalez-Colaso, and Steve A. N. Goldstein. "Opening and Closing of KcnkØ Potassium Leak Channels Is Tightly Regulated." Journal of General Physiology 116, no. 5 (October 30, 2000): 721–34. http://dx.doi.org/10.1085/jgp.116.5.721.
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Potassium-selective leak channels control neuromuscular function through effects on membrane excitability. Nonetheless, their existence as independent molecular entities was established only recently with the cloning of KCNKØ from Drosophila melanogaster. Here, the operating mechanism of these 2 P domain leak channels is delineated. Single KCNKØ channels switch between two long-lived states (one open and one closed) in a tenaciously regulated fashion. Activation can increase the open probability to ∼1, and inhibition can reduce it to ∼0.05. Gating is dictated by a 700-residue carboxy-terminal tail that controls the closed state dwell time but does not form a channel gate; its deletion (to produce a 300-residue subunit with two P domains and four transmembrane segments) yields unregulated leak channels that enter, but do not maintain, the closed state. The tail integrates simultaneous input from multiple regulatory pathways acting via protein kinases C, A, and G.
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Hu, Yirui, and Donald R. Hoover. "Non-randomized and randomized stepped-wedge designs using an orthogonalized least squares framework." Statistical Methods in Medical Research 27, no. 4 (July 10, 2016): 1202–18. http://dx.doi.org/10.1177/0962280216657852.
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Randomized stepped-wedge (R-SW) designs are increasingly used to evaluate interventions targeting continuous longitudinal outcomes measured at T-fixed time points. Typically, all units start out untreated, and randomly chosen units switch to intervention at sequential time points until all receive intervention. As randomization is not always feasible, non-randomized stepped-wedge (NR-SW) designs (units switching to intervention are not randomly chosen) have attracted researchers. We develop an orthogonlized generalized least squares framework for both R-SW and NR-SW designs. The variance of the intervention effect estimate depends on the number of steps ( S), length of step sizes ( ts), and number of units ( ns) switched at each step ( s=1,…, S). If all other design parameters are equal, this variance is higher for the NR-SW than for the equivalent R-SW design (particularly if the intercepts of non-randomly stepped switching strata are analyzed as fixed effects). We focus on balanced stepped-wedge (BR-SW, BNR-SW) designs (where ts and ns remain constant across s) to obtain insights into optimality for variance of the estimated intervention effect. As previously observed for the BR-SW, the optimal choice for number of time points at each step is also [Formula: see text] for the BNR-SW. In our examples, when compared to BR-SW designs, equivalent BNR-SW designs even with intercepts of non-randomly stepped switching strata analyzed using fixed effects sacrifice little efficiency given an intra-unit repeated measure correlation [Formula: see text]. Compared to traditional difference-in-differences designs, optimal BNR-SW designs are more efficient with the ratio of variances of these designs converging to 0.75 when T > 10. We illustrate these findings using longitudinal outcomes in long-term care facilities.
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Guo, Rong, Qi Liu, Junlin Li, and Yong Xu. "Response Statistics of a Shape Memory Alloy Oscillator with Random Excitation." Applied Sciences 11, no. 21 (October 29, 2021): 10175. http://dx.doi.org/10.3390/app112110175.
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This paper aimed to explore analytically the influences of random excitation on a shape memory alloy (SMA) oscillator. Firstly, on the basis of the deterministic SMA model under a harmonic excitation, we introduce a stochastic SMA model with a narrow-band random excitation. Subsequently, a theoretical analysis for the proposed SMA model was achieved through a multiple-scale method coupled with a perturbation technique. All of the obtained approximate analytical solutions were verified by numerical simulation results, and good agreements were observed. Then, effects of the random excitation and the temperature value on the system responses were investigated in detail. Finally, we found that stochastic switch and bifurcation can be induced by the random fluctuation, which were further illustrated through time history and steady-state probability density function. These results indicate that the random excitation has a significant impact on dynamics of the SMA model. This research provides a certain theoretical basis for the design and vibration control of the SMA oscillator in practical application.
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Ceron, Andrea. "Intra-party politics in 140 characters." Party Politics 23, no. 1 (July 9, 2016): 7–17. http://dx.doi.org/10.1177/1354068816654325.
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Scholars have emphasized the need to deepen investigation of intraparty politics. Recent studies look at social media as a source of information on the ideological preferences of politicians and political actors. In this regard, the present article tests whether social media messages published by politicians are a suitable source of data. It applies quantitative text analysis to the public statements released by politicians on social media in order to measure intraparty heterogeneity and assess its effects. Three different applications to the Italian case are discussed. Indeed, the content of messages posted online is informative on the ideological preferences of politicians and proved to be useful to understand intraparty dynamics. Intraparty divergences measured through social media analysis explain: (a) a politician’s choice to endorse one or another party leader, (b) a politician’s likelihood to switch off from his or her parliamentary party group; and (c) a politician’s probability to be appointed as a minister.
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MURPHY, F. C., A. MICHAEL, T. W. ROBBINS, and B. J. SAHAKIAN. "Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance." Psychological Medicine 33, no. 3 (April 2003): 455–67. http://dx.doi.org/10.1017/s0033291702007018.
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Background. Recent evidence suggests that an abnormal response to performance feedback may contribute to the wide-ranging neuropsychological deficits typically associated with depressive illness. The present research sought to determine whether the inability of depressed patients to utilize performance feedback advantageously is equally true for accurate and misleading feedback.Method. Patients with major depression and matched controls completed: (1) a visual discrimination and reversal task that featured intermittent and misleading negative feedback; and (2) feedback and no-feedback versions of a computerised test of spatial working memory. In the feedback version, negative feedback was accurate, highly informative, and could be used as a mnemonic aid.Results. On the Probability Reversal task, depressed patients were impaired in their ability to maintain response set in the face of misleading negative feedback as shown by their increased tendency to switch responding to the ‘incorrect’ stimulus following negative reinforcement, relative to that of controls. Patients' ability to acquire and reverse the necessary visual discrimination was unimpaired. On the Spatial Working Memory task, depressed patients made significantly more between-search errors than controls on the most difficult trials, but their ability to use negative feedback to facilitate performance remained intact.Conclusions. The present results suggest that feedback can have different effects in different contexts. Misleading, negative feedback appears to disrupt the performance of depressed patients, whereas negative but accurate feedback does not. These findings are considered in the context of recent studies on reinforcement systems and their associated neurobiological substrates.
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Latimer, NR, IR White, KR Abrams, and U. Siebert. "Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?" Statistical Methods in Medical Research 28, no. 8 (June 25, 2018): 2475–93. http://dx.doi.org/10.1177/0962280218780856.
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Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes, treatment effect changes over time, survival function shapes, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival that would be observed in the absence of switching, up to the end of trial follow-up. We found that analyses which re-censored usually produced negative bias (i.e. underestimating control group restricted mean survival and overestimating the treatment effect), whereas analyses that did not re-censor consistently produced positive bias which was often smaller in magnitude than the bias associated with re-censored analyses, particularly when the treatment effect was high and the switching proportion was low. The RPSFTM with re-censoring generally resulted in increased bias compared to the other methods. We believe that analyses should be conducted with and without re-censoring, as this may provide decision-makers with useful information on where the true treatment effect is likely to lie. Incorporating re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects.
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Van Leeuwen, Travis E., Oliver E. Hooker, Neil B. Metcalfe, and Colin E. Adams. "Differences in diet-induced flexibility in morphology and growth in a partially migratory species." Canadian Journal of Fisheries and Aquatic Sciences 73, no. 3 (March 2016): 358–65. http://dx.doi.org/10.1139/cjfas-2015-0300.
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Partial migration, in which some individuals of a population migrate while other individuals remain resident, is generally associated with ontogenetic shifts to better feeding or as a response to adversity, but its underlying mechanisms remain relatively unknown. Brown trout (Salmo trutta) exhibit partial migration, with some individuals remaining in fresh water (freshwater-resident) while others undertake an anadromous migration, gain most of their adult size at sea, and then return to fresh water to spawn. The option adopted by an individual trout is thought to be partly determined by its growth performance in early life, which in the stochastic and dynamic environment of freshwater streams may be dependent on its flexibility. To examine potential effects of parent type on phenotypic flexibility, we measured the metabolism, growth, and morphology of full-sibling groups of offspring from freshwater-resident and anadromous parents both before and after a switch in diet. We found that fry had a higher growth rate and a more rounded head and body shape when reared on chironomid larvae compared with when they were reared on Daphnia, but diet had no effect on standard metabolic rate. Interestingly, offspring of anadromous parents were less able to maintain their growth rate when fed on Daphnia than were those of freshwater-residents and showed a correspondingly greater increase in growth following a switch from Daphnia to chironomid larvae. Offspring of anadromous parents also showed less morphological flexibility in response to diet than did the offspring of freshwater-residents. We discuss how the migration history of the parents might interact with phenotypic flexibility in early life to influence the migration probability of the offspring.
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Armisen, R., J. Sierralta, P. Velez, D. Naranjo, and B. A. Suarez-Isla. "Modal gating in neuronal and skeletal muscle ryanodine-sensitive Ca2+ release channels." American Journal of Physiology-Cell Physiology 271, no. 1 (July 1, 1996): C144—C153. http://dx.doi.org/10.1152/ajpcell.1996.271.1.c144.
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The bursting behavior of ryanodine-sensitive single Ca2+ release channels present in chicken cerebellum endoplasmic reticulum (ER), rat hippocampus ER, and frog and rabbit skeletal muscle sarcoplasmic reticulum was established. Unconditional dwell time distributions fitted by the maximum likelihood method reveal at least three open and closed exponential components. Trains of low open probability (P(o)) bursts were interspersed with trains of high P(o) bursts (> or = 0.8) in all the ryanodine receptor isotypes tested. The gating kinetics of the Ca2+ release channels were defined in long recordings by analyzing burst sequences and gamma distributions of average intraburst open (T(o)) and closed times (Tc). The gamma distributions of T(o) had two gamma components, suggesting the existence of two distinct burst types. In contrast, the gamma distributions of Tc had only one component. The correlation between consecutive burst pairs was defined in terms of T(o) and then statistically tested by 2 x 2 matrix contingency analysis. The probability that the ubiquitous sequential burst pattern was generated by random occurrence was < 0.01 (two-tailed Fisher's exact test). Temporal correlations were observed in all ryanodine receptor isotypes under a variety of experimental conditions. These data strongly suggest that single Ca2+ release channels switch slowly between modes of gating. We propose that the effects of agonists of Ca2+ release channels such as Ca2+ itself can be explained as concentration-dependent changes in the availability of each mode.
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Mason, Doran M., Timothy B. Johnson, and James F. Kitchell. "Consequences of prey fish community dynamics on lake trout (Salvelinus namaycush) foraging efficiency in Lake Superior." Canadian Journal of Fisheries and Aquatic Sciences 55, no. 5 (May 1, 1998): 1273–84. http://dx.doi.org/10.1139/f98-007.
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We used a size-structured model, indexed by age, that combines bioenergetics and foraging theory to evaluate the effects of prey fish community structure (species dominance, size structure, and density) on the diet and net foraging efficiency of lake trout (Salvelinus namaycush) in Lake Superior. Prey size structure was important for young lake trout but decreased in importance for older lake trout, especially with increasing prey density. The model predicted that rainbow smelt (Osmerus mordax) should dominate the diet of young lake trout due to the size-dependent capture limitations of larger prey. In contrast, lake herring (Coregonus artedi) should dominate the diet of oldest lake trout owing to a higher net energy return than rainbow smelt. Model results are consistent with age-specific diet and size-at-age of lake trout during the last 40 years. Diets of intermediate-sized lake trout do not reflect the recent resurgence of lake herring populations. Absence of a dietary switch is probably due to higher capture probability for rainbow smelt. Lake trout growth and production will likely be highest with a mixed prey species assemblage of young rainbow smelt and older lake herring.
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Palmer, L. G., and G. Frindt. "Gating of Na channels in the rat cortical collecting tubule: effects of voltage and membrane stretch." Journal of General Physiology 107, no. 1 (January 1, 1996): 35–45. http://dx.doi.org/10.1085/jgp.107.1.35.
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The gating kinetics of apical membrane Na channels in the rat cortical collecting tubule were assessed in cell-attached and inside-out excised patches from split-open tubules using the patch-clamp technique. In patches containing a single channel the open probability (Po) was variable, ranging from 0.05 to 0.9. The average Po was 0.5. However, the individual values were not distributed normally, but were mainly < or = 0.25 or > or = 0.75. Mean open times and mean closed times were correlated directly and inversely, respectively, with Po. In patches where a sufficient number of events could be recorded, two time constants were required to describe the open-time and closed-time distributions. In most patches in which basal Po was < 0.3 the channels could be activated by hyperpolarization of the apical membrane. In five such patches containing a single channel hyperpolarization by 40 mV increased Po by 10-fold, from 0.055 +/- 0.023 to 0.58 +/- 0.07. This change reflected an increase in the mean open time of the channels from 52 +/- 17 to 494 +/- 175 ms and a decrease in the mean closed time from 1,940 +/- 350 to 336 +/- 100 ms. These responses, however, could not be described by a simple voltage dependence of the opening and closing rates. In many cases significant delays in both the activation by hyperpolarization and deactivation by depolarization were observed. These delays ranged from several seconds to several tens of seconds. Similar effects of voltage were seen in cell-attached and excised patches, arguing against a voltage-dependent chemical modification of the channel, such as a phosphorylation. Rather, the channels appeared to switch between gating modes. These switches could be spontaneous but were strongly influenced by changes in membrane voltage. Voltage dependence of channel gating was also observed under whole-cell clamp conditions. To see if mechanical perturbations could also influence channel kinetics or gating mode, negative pressures of 10-60 mm Hg were applied to the patch pipette. In most cases (15 out of 22), this maneuver had no significant effect on channel behavior. In 6 out of 22 patches, however, there was a rapid and reversible increase in Po when the pressure was applied. In one patch, there was a reversible decrease. While no consistent effects of pressure could be documented, membrane deformation could contribute to the variation in Po under some conditions.
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Migliore, Alberto, Giuseppe Pompilio, Davide Integlia, Joe Zhuo, and Evo Alemao. "Cycling of tumor necrosis factor inhibitors versus switching to different mechanism of action therapy in rheumatoid arthritis patients with inadequate response to tumor necrosis factor inhibitors: a Bayesian network meta-analysis." Therapeutic Advances in Musculoskeletal Disease 13 (January 2021): 1759720X2110026. http://dx.doi.org/10.1177/1759720x211002682.
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Introduction: For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching. Methods: We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993. Results: We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96–1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40–0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model. Discussion: Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy. Plain language summary Assessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literature Rheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death. Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues. When TNFi therapy is unsuccessful, the options are to “cycle” to another TNFi or to “switch” to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails. This study analyzed 25 published studies in which patients were either “cycled” to another TNFi or “switched” to a drug with a different MOA after unsuccessful treatment with an initial TNFi. The results showed that “switching” to a drug with a different MOA was a better treatment strategy than “cycling” to another TNFi; “switching” increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.
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Kang, Po Wei, Nourdine Chakouri, Johanna Diaz, Gordon F. Tomaselli, David T. Yue, and Manu Ben-Johny. "Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes." Proceedings of the National Academy of Sciences 118, no. 21 (May 21, 2021): e2025085118. http://dx.doi.org/10.1073/pnas.2025085118.
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In cardiomyocytes, NaV1.5 channels mediate initiation and fast propagation of action potentials. The Ca2+-binding protein calmodulin (CaM) serves as a de facto subunit of NaV1.5. Genetic studies and atomic structures suggest that this interaction is pathophysiologically critical, as human mutations within the NaV1.5 carboxy-terminus that disrupt CaM binding are linked to distinct forms of life-threatening arrhythmias, including long QT syndrome 3, a “gain-of-function” defect, and Brugada syndrome, a “loss-of-function” phenotype. Yet, how a common disruption in CaM binding engenders divergent effects on NaV1.5 gating is not fully understood, though vital for elucidating arrhythmogenic mechanisms and for developing new therapies. Here, using extensive single-channel analysis, we find that the disruption of Ca2+-free CaM preassociation with NaV1.5 exerts two disparate effects: 1) a decrease in the peak open probability and 2) an increase in persistent NaV openings. Mechanistically, these effects arise from a CaM-dependent switch in the NaV inactivation mechanism. Specifically, CaM-bound channels preferentially inactivate from the open state, while those devoid of CaM exhibit enhanced closed-state inactivation. Further enriching this scheme, for certain mutant NaV1.5, local Ca2+ fluctuations elicit a rapid recruitment of CaM that reverses the increase in persistent Na current, a factor that may promote beat-to-beat variability in late Na current. In all, these findings identify the elementary mechanism of CaM regulation of NaV1.5 and, in so doing, unravel a noncanonical role for CaM in tuning ion channel gating. Furthermore, our results furnish an in-depth molecular framework for understanding complex arrhythmogenic phenotypes of NaV1.5 channelopathies.
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Stoklosa, Michal, Fastone Goma, Nigar Nargis, Jeffrey Drope, Grieve Chelwa, Zunda Chisha, and Geoffrey T. Fong. "Price, tax and tobacco product substitution in Zambia: findings from the ITC Zambia Surveys." Tobacco Control 28, Suppl 1 (March 24, 2018): s45—s52. http://dx.doi.org/10.1136/tobaccocontrol-2017-054037.
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BackgroundIn Zambia, the number of cigarette users is growing, and the lack of strong tax policies is likely an important cause. When adjusted for inflation, levels of tobacco tax have not changed since 2007. Moreover, roll-your-own (RYO) tobacco, a less-costly alternative to factory-made (FM) cigarettes, is highly prevalent.Data and methodsWe modelled the probability of FM and RYO cigarette smoking using individual-level data obtained from the 2012 and 2014 waves of the International Tobacco Control (ITC) Zambia Survey. We used two estimation methods: the standard estimation method involving separate random effects probit models and a method involving a system of equations (incorporating bivariate seemingly unrelated random effects probit) to estimate price elasticities of FM and RYO cigarettes and their cross-price elasticities.ResultsThe estimated price elasticities of smoking prevalence are −0.20 and −0.03 for FM and RYO cigarettes, respectively. FM and RYO are substitutes; that is, when the price of one of the products goes up, some smokers switch to the other product. The effects are stronger for substitution from FM to RYO than vice versa.ConclusionsThis study affirms that increasing cigarette tax with corresponding price increases could significantly reduce cigarette use in Zambia. Furthermore, reducing between-product price differences would reduce substitution from FM to RYO. Since RYO use is associated with lower socioeconomic status, efforts to decrease RYO use, including through tax/price approaches and cessation assistance, would decrease health inequalities in Zambian society and reduce the negative economic consequences of tobacco use experienced by the poor.
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Kwun, Min Jung, Marco R. Oggioni, Stephen D. Bentley, Christophe Fraser, and Nicholas J. Croucher. "Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae." Genes 10, no. 9 (September 13, 2019): 707. http://dx.doi.org/10.3390/genes10090707.
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A diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae cells, but many isolates remain uninfected. The best-characterised defences against horizontal transmission of MGEs are restriction-modification systems (RMSs), of which there are two phase-variable examples in S. pneumoniae. Additionally, the transformation machinery has been proposed to limit vertical transmission of chromosomally integrated MGEs. This work describes how these mechanisms can act in concert. Experimental data demonstrate RMS phase variation occurs at a sub-maximal rate. Simulations suggest this may be optimal if MGEs are sometimes vertically inherited, as it reduces the probability that an infected cell will switch between RMS variants while the MGE is invading the population, and thereby undermine the restriction barrier. Such vertically inherited MGEs can be deleted by transformation. The lack of between-strain transformation hotspots at known prophage att sites suggests transformation cannot remove an MGE from a strain in which it is fixed. However, simulations confirmed that transformation was nevertheless effective at preventing the spread of MGEs into a previously uninfected cell population, if a recombination barrier existed between co-colonising strains. Further simulations combining these effects of phase variable RMSs and transformation found they synergistically inhibited MGEs spreading, through limiting both vertical and horizontal transmission.
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Heo, Moonseong, Paul Meissner, Alain H. Litwin, Julia H. Arnsten, M. Diane McKee, Alison Karasz, Paula McKinley, et al. "Preference option randomized design (PORD) for comparative effectiveness research: Statistical power for testing comparative effect, preference effect, selection effect, intent-to-treat effect, and overall effect." Statistical Methods in Medical Research 28, no. 2 (November 9, 2017): 626–40. http://dx.doi.org/10.1177/0962280217734584.
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Comparative effectiveness research trials in real-world settings may require participants to choose between preferred intervention options. A randomized clinical trial with parallel experimental and control arms is straightforward and regarded as a gold standard design, but by design it forces and anticipates the participants to comply with a randomly assigned intervention regardless of their preference. Therefore, the randomized clinical trial may impose impractical limitations when planning comparative effectiveness research trials. To accommodate participants’ preference if they are expressed, and to maintain randomization, we propose an alternative design that allows participants’ preference after randomization, which we call a “preference option randomized design (PORD)”. In contrast to other preference designs, which ask whether or not participants consent to the assigned intervention after randomization, the crucial feature of preference option randomized design is its unique informed consent process before randomization. Specifically, the preference option randomized design consent process informs participants that they can opt out and switch to the other intervention only if after randomization they actively express the desire to do so. Participants who do not independently express explicit alternate preference or assent to the randomly assigned intervention are considered to not have an alternate preference. In sum, preference option randomized design intends to maximize retention, minimize possibility of forced assignment for any participants, and to maintain randomization by allowing participants with no or equal preference to represent random assignments. This design scheme enables to define five effects that are interconnected with each other through common design parameters—comparative, preference, selection, intent-to-treat, and overall/as-treated—to collectively guide decision making between interventions. Statistical power functions for testing all these effects are derived, and simulations verified the validity of the power functions under normal and binomial distributions.
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de Pedro, Luis, Francisco Beitia, and José Tormos. "Two Better Than One? Potential Effects of Intraguild Predation on the Biological Control of Ceratitis capitata (Diptera: Tephritidae) by the Parasitoid Aganaspis daci (Hymenoptera: Figitidae) and the Predator Pseudoophonus rufipes (Coleoptera: Carabidae)." Agronomy 13, no. 1 (December 27, 2022): 87. http://dx.doi.org/10.3390/agronomy13010087.
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The use of more than one species to manage a single insect pest is a common practice among biological control programs. However, the beneficial effects of natural enemies are not always additive, which in many cases may be attributed to interspecific interactions such as intraguild predation (IGP). Herein, we investigated the potential IGP between two relevant natural enemies of the Medfly (Ceratitis capitata), the predator Pseudoophonus rufipes and the parasitoid Aganaspis daci, as well as the possible implications of this phenomenon in their efficiency as biocontrol agents. To this end, we assessed their functional responses and different demographic parameters when acting alone and together against C. capitata under laboratory conditions. Coexistence led to a switch in the functional response of both species, from type III to type II in A. daci and the opposite in P. rufipes. Regarding demographic parameters, coexistence resulted in higher parasitoidism and population reduction by A. daci only at low host densities, probably due to competition pressure. In the same circumstances, P. rufipes reduced its predatory activity, rejecting those larvae that were presumably parasitized and causing negligible IGP. At high Medfly densities, A. daci efficiency decreased, and the reduced encounter probability enhanced the predatory activity by P. rufipes. As a result of these trends, Medfly population reduction reached almost 100% at all densities, which suggests an additive effect of both natural enemies and recommends combined releases of these agents as a strategy for the control of the Medfly.
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Myint, Phyo Thazin, Amani Erra, Taha Alrifai, Salman Syed, Bibek Singh Pannu, Shyam Chalise, and Kelley E. Kozma. "Appropriateness of Heparin-Induced Thrombocytopenia (HIT) Testing and the Reliability of 4-Ts Scoring in Critically Ill Patients." Blood 132, Supplement 1 (November 29, 2018): 4988. http://dx.doi.org/10.1182/blood-2018-99-114788.
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Abstract Introduction: Thrombocytopenia is a common occurrence in critically ill patients and results in an array of diagnostic workup. Heparin induced thrombocytopenia (HIT) is one of the most frequently ordered tests in this scenario, although it is a less common cause (0.02-0.5%) The over testing and treatment of HIT in Intensive Care Unit (ICU) can lead to a change in medications, and result in side effects, increased ICU length of stay and increased costs. Current guidelines recommend 4-Ts criteria to evaluate the clinical HIT probability in general population, but it may also be used in Intensive Care Unit (ICU) patients. Here, we want to analyze the the usage of 4Ts score in a community hospital and to understand its correlation with HIT testing to see if HIT testing could have been avoided. Methods: We performed a retrospective chart review of adult patients who underwent testing for Heparin Induced Thrombocytopenia anti-platelet factor 4 antibody (anti- PF4 Ab) in ICU at our institution from 03/01/2012 to 02/01/2018. The primary outcomes were set to identify (1) the extent of inappropriate of HIT testing and its consequences in patients with low 4Ts scores, and (2) if 4Ts score as a potential predictor of length of stay and mortality in ICU. As a secondary outcome, we assessed if Body Mass Index (BMI) and Recent Surgery are related to false positive anti-PF4 Ab test. Kruskal-Wallis test and Fisher Exact test were used. Results: A total of 66 patients were identified. The mean age was 64 yr and the male-female ratio was similar. 40 patients had recent surgery in the past 3 months. The cause of thrombocytopenia other than HIT was possible or definite in 62 patients with sepsis being the most common cause (56.45%). 30 patients had low probability 4-Ts scores, 28 had intermediate and 7 had high probability. HIT was confirmed (Serotonin Release Assay-SRA positive) in 0%, 7.14% and 12.5% of patients with low, intermediate and high probability 4Ts scores, respectively. In the patients with low probability 4Ts and anti-PF4 Ab testing, heparin was held in 24 (80%) and the anti-coagulation was switched (to either fondaparinux or argatroban) in 10 (33.33%). In those patients with anticoagulation switch, 3 had minor bleeding. There was no difference in the ICU length of stay (p=0.1712) and mortality (p=0.149) between patients with low, intermediate and high probability 4Ts scores. Patients with BMI ≥40 kg/m2 had twice the percentage of false positive anti-PF4 Ab testing compared with the rest, but the results were not significant (p=0.285). Recent surgery was not related to the false positive anti-PF4 Ab testing (p=1). Conclusion: As no patient with low-probability 4Ts score had confirmed HIT, low 4Ts may be a good estimator of the unlikeliness of HIT even in critically ill patients. We found discrepancy in the recommendations and usage of Anti-PF4 Ab testing in our institution. This has resulted in switching of heparin to other, more expensive anti-coagulations. This may very well be the situation in many other similar institutions. This could partly be due to lack of awareness of HIT testing guidelines in the critical care setting. We recommend the use of 4Ts scoring and more sensible testing and treatment of HIT in ICU patients. Although we could not demonstrate the statistical association between morbid obesity and false positive anti-PF4 Ab, our study might have been underpowered by low subgroup population of such patients. We propose further studies about HIT testing and treatment to include morbidly obese patients as a separate sub-group. Disclosures No relevant conflicts of interest to declare.
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Kamboh, Muhammad Iqbal, Nazri Mohd Nawi, and Radiah Bt. Mohamad. "An improved flower pollination solution for economic dispatch with valve point effect." Indonesian Journal of Electrical Engineering and Computer Science 22, no. 2 (May 1, 2021): 629. http://dx.doi.org/10.11591/ijeecs.v22.i2.pp629-637.
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<span>The economic dispatch is used to find the best optimal output of power generation at the lowest operating cost of each generator, to fulfill the requirements of the consumer. To get a practical solution, several constraints have to be considered, like transmission losses, the valve point effect, prohibited operating region, and emissions. In this research, the valve point effect is to be considered which increases the complexity of the problem due to its ripple effect on the fuel cost curve. Economic load dispatch problems are well-known optimization problems. Many classical and meta-heuristic techniques have been used to get better solutions. However, there is still room for improvement to get an optimal solution for the economic dispatch problem. In this paper, an Improved Flower Pollination Algorithm with dynamic switch probability and crossover operator is proposed to solve these complex optimization problems. The performance of our proposed technique is analyzed against fast evolutionary programming (FEP), modified fast evolutionary programming (MFEP), improved fast evolutionary programming (IFEP), artificial bee colony algorithm (ABC), modified particle swarm optimization (MPSO) and standard flower pollination algorithm (SFPA) using three generator units and thirteen thermal power generation units, by including the effects of valve point loading unit and without adding it. The proposed technique has outperformed other methods in terms of the lowest operating fuel cost.</span>
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Libby, Eric, Peter L. Conlin, Ben Kerr, and William C. Ratcliff. "Stabilizing multicellularity through ratcheting." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1701 (August 19, 2016): 20150444. http://dx.doi.org/10.1098/rstb.2015.0444.
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The evolutionary transition to multicellularity probably began with the formation of simple undifferentiated cellular groups. Such groups evolve readily in diverse lineages of extant unicellular taxa, suggesting that there are few genetic barriers to this first key step. This may act as a double-edged sword: labile transitions between unicellular and multicellular states may facilitate the evolution of simple multicellularity, but reversion to a unicellular state may inhibit the evolution of increased complexity. In this paper, we examine how multicellular adaptations can act as evolutionary ‘ratchets’, limiting the potential for reversion to unicellularity. We consider a nascent multicellular lineage growing in an environment that varies between favouring multicellularity and favouring unicellularity. The first type of ratcheting mutations increase cell-level fitness in a multicellular context but are costly in a single-celled context, reducing the fitness of revertants. The second type of ratcheting mutations directly decrease the probability that a mutation will result in reversion (either as a pleiotropic consequence or via direct modification of switch rates). We show that both types of ratcheting mutations act to stabilize the multicellular state. We also identify synergistic effects between the two types of ratcheting mutations in which the presence of one creates the selective conditions favouring the other. Ratcheting mutations may play a key role in diverse evolutionary transitions in individuality, sustaining selection on the new higher-level organism by constraining evolutionary reversion. This article is part of the themed issue ‘The major synthetic evolutionary transitions’.
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Kim, Aleksey E., Evgeniy B. Shustov, Aleksey V. Lemeshchenko, and Vasily N. Tsygan. "Pathophysiological bases of maladjustment formation in high mountains and polar zones." Bulletin of the Russian Military Medical Academy 23, no. 3 (November 3, 2021): 215–22. http://dx.doi.org/10.17816/brmma71182.
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The pathophysiological features of the development of maladjustment under mountain-cold conditions as a manifestation of the syndrome of mutual burdening are considered. In this study, contents of various literary sources, characterizing a persons resistance to the effects of a complex of factors under high mountains and polar zones conditions, were analyzed. With the simultaneous exposure to hypoxia and hypothermia from a pathophysiological point of view, intersecting links of terminological paths, often having diametrically opposite dynamics of changes in the characterized concepts, will be significant. Thus, in the terminological mitochondrial pathway of energy metabolism, uncoupling proteins are present, which, to increase the resistance to hypothermia, should be activated to switch the energy metabolism to predominantly use fatty acids. However, hypoxic conditions should be suppressed to maintain the level of adenosine triphosphate acid available for cells. In the terminological tract of compensatory reactions in response to hypoxemia, the volume of pulmonary ventilation is released, which must increase to improve tolerance to hypoxia, which, under mountain-cold conditions, increased heat loss and promote the deterioration of the condition, i.e., tolerance to low temperatures. Under hypoxic and hypothermic conditions, a synergistic interaction can form, which can be manifested by the development of a syndrome of mutual burdening, which will result in a significant decrease in the functional capabilities of the body, result, and productivity. Maladjustment to mountain cold, with maximum probability, will manifest as disorders of the central nervous system, decreased physical performance, depletion of the functional and regulatory reserves of the body, functional immunodeficiency, decreased regenerative potential, and development of endogenous intoxication. With a high degree of probability, a significant synergistic interaction of hypoxia and hypothermia can be found in relation to the indicators of pulmonary ventilation, blood gases (hypercapnia), acidbase balance (gas alkalosis and lactic acidosis), heart rate (tachycardia), blood pressure (hypotension), central venous pressure (increase), blood viscosity (increase) and its coagulability (hypercoagulation), peroxide and free radical oxidation (activation), and protein catabolism (increase). These changes will negatively affect the functional state of specialists performing complex professional tasks in polar latitudes.
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Prole, David L., Pedro A. Lima, and Neil V. Marrion. "Mechanisms Underlying Modulation of Neuronal KCNQ2/KCNQ3 Potassium Channels by Extracellular Protons." Journal of General Physiology 122, no. 6 (November 24, 2003): 775–93. http://dx.doi.org/10.1085/jgp.200308897.
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Changes in extracellular pH occur during both physiological neuronal activity and pathological conditions such as epilepsy and stroke. Such pH changes are known to exert profound effects on neuronal activity and survival. Heteromeric KCNQ2/3 potassium channels constitute a potential target for modulation by H+ ions as they are expressed widely within the CNS and have been proposed to underlie the M-current, an important determinant of excitability in neuronal cells. Whole-cell and single-channel recordings demonstrated a modulation of heterologously expressed KCNQ2/3 channels by extracellular H+ ions. KCNQ2/3 current was inhibited by H+ ions with an IC50 of 52 nM (pH 7.3) at −60 mV, rising to 2 μM (pH 5.7) at −10 mV. Neuronal M-current exhibited a similar sensitivity. Extracellular H+ ions affected two distinct properties of KCNQ2/3 current: the maximum current attainable upon depolarization (Imax) and the voltage dependence of steady-state activation. Reduction of Imax was antagonized by extracellular K+ ions and affected by mutations within the outer-pore turret, indicating an outer-pore based process. This reduction of Imax was shown to be due primarily to a decrease in the maximum open-probability of single KCNQ2/3 channels. Single-channel open times were shortened by acidosis (pH 5.9), while closed times were increased. Acidosis also recruited a longer-lasting closed state, and caused a switch of single-channel activity from the full-conductance state (∼8 pS) to a subconductance state (∼5 pS). A depolarizing shift in the activation curve of macroscopic KCNQ2/3 currents and single KCNQ2/3 channels was caused by acidosis, while alkalosis caused a hyperpolarizing shift. Activation and deactivation kinetics were slowed by acidosis, indicating specific effects of H+ ions on elements involved in gating. Contrasting modulation of homomeric KCNQ2 and KCNQ3 currents revealed that high sensitivity to H+ ions was conferred by the KCNQ3 subunit.
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Bouzid, Leyla, Mohand Hamizi, Naceur-Eddine Hannachi, Aghiles Nekmouche, and Karim Akkouche. "Plastic hinges mechano-reliability analysis in the beams of RC frames structures." World Journal of Engineering 17, no. 5 (August 4, 2020): 719–32. http://dx.doi.org/10.1108/wje-02-2020-0069.
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Purpose The purpose of this study is to establish a relationship between causes and effects, the respect of materials characteristics values [concrete compressive strength (fc) and steel yield stress (fy)] and the norms of the construction dispositions value (covers). This study is motivated by the post-seismic damages related to the plastification of the reinforced concrete (RC)/beams sections, named plastic hinges. The results are given by fragility curves representing the failure probability (Pf) of the plastic hinges versus covers value. Design/methodology/approach A mechanical-reliability coupling methodology is proposed and performed on three frames (three, six and nine storey). For each frame, seven covers the value of reinforcement steel bars has been taken into account in the beams. After definition of the limit state function G(x), a process of idea to twin-track; deterministic and probabilistic, is considered. Thus, numerical simulations are carried out under ETABS© software, to extract a soliciting moments Ms(x). Then, ultimate moments Mu(x), the result of reliability approach are calculated using Monte Carlo Simulations. In this step, two random variables; concrete compressive strength in 28 days of age (fc) and steel yield stress (fy), have been studied. Findings In the mechanical study, the results show that, the first plastic hinge appears at the beams for all frames. In the reliability study, the (fy) variation shows that all plastic hinges are in failure domain, nevertheless, the (fc) variation leads to have all sections in the safety domain, except A7 and B7 models. The failure probability (Pf) calculation according to (fc) and (fy) shows that an absolute error of 0.5 cm in the steel bars covers can switch the frame from the safety domain to the failure domain. Originality/value The plastic hinges reliability of the RC/ frame structures is independent on the high of the structure. The (fc) random variable according to the used distribution law does not affect the reliability (safety or failure). However, the impact of the steel yield stress variation (fy) is not negligible. The errors in covers affect considerably the strength of the elements.
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Fischer, H., and T. E. Machen. "CFTR displays voltage dependence and two gating modes during stimulation." Journal of General Physiology 104, no. 3 (September 1, 1994): 541–66. http://dx.doi.org/10.1085/jgp.104.3.541.
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The patch-clamp technique in conjunction with current noise analysis was employed to clarify the events underlying the regulation of the CFTR (cystic fibrosis transmembrane conductance regulator) during cAMP-dependent stimulation. 3T3 fibroblast cells expressing the CFTR were stimulated in cell-attached mode with forskolin. The number (N) of activated channels per patch ranged from 1 to approximately 100. In true single-channel recordings, CFTR's gating was best described by two open states (approximately 5 and approximately 100 ms) and three closed states (< or = 5, approximately 100, and approximately 1,000 ms). Current noise analysis resulted in spectra containing two distinct Lorentzian noise components with corner frequencies of 1.3 Hz and approximately 50 Hz, respectively. Single-channel time constants were dependent on voltage. The fastest closed state increased its contribution from 48% at +100 mV to 87% at -100 mV, and the medium open state reduced its length to one half, resulting in gating dominated by fast events. Similarly, the fast Lorentzian increased its amplitude, and its corner frequency increased from 44 Hz at +100 mV to 91 Hz at -100 mV, while the slow Lorentzian was voltage independent. In multi-channel recordings N.Po (i.e., N times open probability) increased significantly, on average by 52% between -90 and +90 mV. Stimulation with forskolin increased Po of CFTR to approximately 0.5, which resulted from a decrease of the longest closed state while the faster open and closed states were unaffected. Neither corner frequency was affected during stimulation. Recordings from multichannel patches revealed in addition, unique, very long channel openings (high Po mode, average 13 s). Channels exhibiting high Po (i.e., Po approximately 1.0) or low Po (i.e., Po approximately 0.5) gating modes were both present in multichannel recordings, and CFTRs switched modes during stimulation. In addition, the switch to the high Po mode appeared to be a cooperative event for channel pairs. High forskolin concentration (i.e., 10 microM) favored transition into the high Po mode, suggesting a cellularly mediated regulation of model switching due to a fundamental change in configuration of the CFTR. Thus, during stimulation the CFTR increased its activity through two distinct effects: the reduction of the long closed state and modal switching to the high Po mode.
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Hernandez, Adrian V., George Bradley, Mohammad Khan, Andrew Fratoni, Anna Gasparini, Yuani M. Roman, Thomas J. Bunz, Daniel Eriksson, Anna-Katharina Meinecke, and Craig I. Coleman. "Rivaroxaban vs. warfarin and renal outcomes in non-valvular atrial fibrillation patients with diabetes." European Heart Journal - Quality of Care and Clinical Outcomes 6, no. 4 (August 20, 2019): 301–7. http://dx.doi.org/10.1093/ehjqcco/qcz047.
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Abstract Aims Vascular calcification is common in diabetic patients. Warfarin has been associated with renovascular calcification and worsening renal function; rivaroxaban may provide renopreservation by decreasing vascular inflammation. We compared the impact of rivaroxaban and warfarin on renal outcomes in diabetic patients with non-valvular atrial fibrillation (NVAF). Methods and results Using United States IBM MarketScan data from January 2011 to December 2017, we identified adults with both NVAF and diabetes, newly-initiated on rivaroxaban or warfarin with ≥12-month insurance coverage prior to anticoagulation initiation. Patients with Stage 5 chronic kidney disease (CKD) or undergoing haemodialysis at baseline were excluded. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weighting (IPTW) based on propensity scores (absolute standardized differences <0.1 achieved for all after adjustment). Outcomes included incidence rates of emergency department/hospital admissions for acute kidney injury (AKI) and the composite of the development of Stage 5 CKD or need for haemodialysis. Patients were followed until an event, index anticoagulant discontinuation/switch, insurance disenrollment, or end-of-data availability. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression. We assessed 10 017 rivaroxaban (22.6% received a reduced dose) and 11 665 warfarin users. In comparison to warfarin, rivaroxaban was associated with lower risks of AKI (HR = 0.83, 95% CI = 0.74–0.92) and development of Stage 5 CKD or need for haemodialysis (HR = 0.82, 95% CI = 0.70–0.96). Sensitivity and subgroup analyses had similar effects as the base-case analysis. Conclusion Rivaroxaban appears to be associated with lower risks of undesirable renal outcomes vs. warfarin in diabetic NVAF patients.
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Adeboyeje, Gboyega, Eleanor Caplan, Yihua Xu, Monica Chase, Nicole Myer, Sheetal Sheth, and Brandon T. Suehs. "Clinical and economic outcomes associated with upfront comprehensive genomic profiling in newly diagnosed advanced lung cancer in the United States from 2018-2020: Evidence from the SEQUENCE study." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 9126. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.9126.
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9126 Background: As the number of approved molecularly-targeted therapies for the treatment of lung cancer increases, the debate continues as to whether a clinical strategy leveraging next-generation sequencing (NGS) comprehensive genomic profiling (CGP) to match patients to targeted treatments is advantageous versus a narrow/single-gene (N/S) panel testing. We examined clinical and economic outcomes of patients with advanced lung cancer (aLC) in the United States (US). Methods: In this retrospective study, newly diagnosed aLC patients aged 65-89 years were identified from a US Medicare Advantage plan from 2018-2020. Patients receiving genomic testing within 90 days of diagnosis and an FDA-approved pharmacotherapy cancer treatment after diagnosis were categorized by initial sequencing with NGS CGP (51+ genes) vs N/S (≤50 genes) panel testing using administrative claims based on previously validated algorithms. We assessed the proportion of patients with an inpatient or emergency department (INP/ED) visit for select outcomes (e.g., neutropenia) within 6 months of start of treatment, all-cause mortality, and PPPM (per patient per month) total healthcare costs through all available follow-up. Genomic testing costs within 90 days of cancer diagnosis were estimated using the Medicare fee schedule. Among patients with treatment within 30 days of testing, we assessed the proportion who did not switch treatment and were alive within 6 months. Descriptive analyses were conducted, and average effects were estimated using inverse probability weighted regression models. Results: We identified 3,532 patients who received genomic testing and pharmacotherapy cancer treatment (NGS CGP, n = 968; N/S, n = 2,564). Characteristics were similar between testing groups. The proportion of patients with INP/ED for outcomes of interest was similar following NGS CGP vs. N/S panels (15.0% vs. 17.8%; IRR [95% CI]: 0.76 [0.57 – 1.02]; p = 0.066), as were mortality (56.2% vs. 59.2%; HR: 1.05 [0.95 - 1.16]; p = 0.323) and PPPM costs (PPPM median cost difference -$575; ratio from regression 0.99, 0.94-1.04; p = 0.228). Among a subgroup of patients treated within 30 days of testing, a higher proportion receiving NGS CGP did not switch treatment and were alive after 6 months (47.6%) vs those receiving N/S panels (39.8%) (OR [95% CI]: 1.33 [1.12 - 1.59]; p = 0.001). Median genomic testing costs were $3,049 for NGS CGP vs. $218 for N/S testing. Conclusions: Outcomes were similar between patients receiving NGS CGP and N/S panel testing. Among patients with treatment within 30 days of testing, upfront NGS CGP was associated with fewer patients switching treatment and 6-month survival. Upfront testing with NGS CGP may represent a beneficial genomic profiling strategy as part of the initial management of patients with aLC.
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Braune, Stefan, Fabian Rossnagel, Heidi Dikow, and Arnfin Bergmann. "Impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany between 2010 and 2018: real-world data from the German NeuroTransData multiple sclerosis registry." BMJ Open 11, no. 8 (August 2021): e042480. http://dx.doi.org/10.1136/bmjopen-2020-042480.
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ObjectiveTo evaluate the impact of drug diversity on treatment effectiveness in relapsing-remitting multiple sclerosis (RRMS) in Germany.DesignThis study employs real-world data captured in-time during clinical visits in 67 German neurology outpatient offices of the NeuroTransData (NTD) multiple sclerosis (MS) registry between 1 January 2010 and 30 June 2019, including 237 976 visits of 17 553 patients with RRMS. Adherence and clinical effectiveness parameters were analysed by descriptive statistics, time-to-event analysis overall and by disease-modifying therapies (DMTs) stratified by administration modes (injectable, oral and infusion). Three time periods were compared: 2010–2012, 2013–2015 and 2016–2018.ResultsBetween 2010 and 2018, an increasing proportion of patients with RRMS were treated with DMTs and treatment was initiated sooner after diagnosis of MS. Introduction of oral DMT temporarily induced higher readiness to switch. Comparing the three index periods, there was a continuous decrease of annualised relapse rates, less frequent Expanded Disability Status Scale (EDSS) progression and increasing periods without relapse, EDSS worsening and with stability of no-evidence-of-disease-activity 2 and 3 criteria, lower conversion rates to secondary progressive MS on oral and on injectable DMTs.ConclusionSparked by the availability of new mainly oral DMTs, RRMS treatment effectiveness improved clinically meaningful between 2010 and 2018. As similar effects were seen for injectable and oral DMTs more than for infusions, a better personalised treatment allocation in many patients is likely. These results indicate that there is an overall beneficial effect for the whole patient with MS population as a result of the greater selection of available DMTs, a benefit beyond the head-to-head comparative efficacy, resulting from an increased probability and readiness to individualise MS therapy.
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Abelenda-Alonso, Gabriela, Alexander Rombauts, Carlota Gudiol, Yolanda Meije, Mercedes Clemente, Lucía Ortega, Carmen Ardanuy, et al. "Impact of comprehensive molecular testing to reduce antibiotic use in community-acquired pneumonia (RADICAP): a randomised, controlled, phase IV clinical trial protocol." BMJ Open 10, no. 8 (August 2020): e038957. http://dx.doi.org/10.1136/bmjopen-2020-038957.
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IntroductionCommunity-acquired pneumonia (CAP) continues to be a major health problem worldwide and is one of the main reasons for prescribing antibiotics. However, the causative agent is often not identified, resulting in antibiotic overtreatment, which is a key driver of antimicrobial resistance and adverse events. We aim to test the hypothesis that comprehensive molecular testing, compared with routine microbiological testing, would be effective in reducing antibiotic use in patients with CAP.Methods and analysisWe will perform a randomised, controlled, open-label clinical trial with two parallel groups (1:1) at two tertiary hospitals between 2020 and 2022. Non-severely immunosuppressed adults hospitalised for CAP will be considered eligible. Patients will be randomly assigned to receive either the experimental diagnosis (comprehensive molecular testing plus routine microbiological testing) or standard diagnosis (only microbiological routine testing). The primary endpoint will be antibiotic consumption measured as days of antibiotic therapy per 1000 patient-days. Secondary endpoints will be de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, days to reaching an aetiological diagnosis, antibiotic-related side effects, length of stay, days to clinical stability, intensive care unit admission, days of mechanical ventilation, hospital readmission up to 30 days after randomisation and death from any cause by 48 hours and 30 days after randomisation. We will need to include 440 subjects to be able to reject the null hypothesis that both groups have equal days of antibiotic therapy per 1000 patient-days with a probability >0.8.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Bellvitge Hospital (AC028/19) and from the Spanish Medicines and Medical Devices Agency, and it is valid for all participating centres under existing Spanish legislation. Results will be presented at international meetings and will be made available to patients, their caregivers and funders.Trial registration numberClinicalTrials: NCT04158492. EudraCT: 2018-004880-29.
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Rocchi, Paolo, and Orlando Panella. "Some probability effects in the classical context." Open Physics 18, no. 1 (August 17, 2020): 512–16. http://dx.doi.org/10.1515/phys-2020-0178.
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AbstractThis article gives an account of a theoretical research subdivided into three parts. The first stage recalls the theorem of large numbers and the theorem a single number which demonstrate how the frequentist and the subjective models of probability can be used according to distinct assumptions. Based on these achievements, the second stage describes the temporal evolution of the random outcome (this article distinguishes the outcome from the random event or phenomenon that produces it). It is proved that the outcome of a single unpredictable event switches from the indeterministic to the deterministic state when the event winds up. The third stage means to show how the theoretical results apply to physical situations.
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Castagnetti, Fausto, Francesco Di Raimondo, Antonio de Vivo, Antonio Spitaleri, Gabriele Gugliotta, Francesco Fabbiano, Isabella Capodanno, et al. "A Population-Based Study of Chronic Myeloid Leukemia Treated with Imatinib in First Line." Blood 128, no. 22 (December 2, 2016): 3076. http://dx.doi.org/10.1182/blood.v128.22.3076.3076.
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Abstract Background. Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapies. However these clinical trials included patients selected according to different inclusion and exclusion criteria, particularly age and comorbidities, and with specific treatment obligations. In daily clinical practice (real life), no inclusion and exclusion criteria do exist, and treatment outcomes depend not only on choice of the first-line TKI, but also on doctor- and patient-choice of second- and third-line TKIs. Aims. To investigate the response and the outcome on first-line imatinib, with switch to 2nd generation TKIs in case of failure or toxicity, in BCR-ABL1+ CML patients enrolled in a population-based registry (real-life setting). Methods. We report here the results from a prospective study, enrolling all newly diagnosed patients (N = 236, median age 60 years) living in two Italian regions, that were registered according to population-based criteria and treated front-line with imatinib. The decision to switch to second-line treatment was up to the Local Investigator (no predefined criteria) Definitions: major molecular response (MMR or MR3.0): BCR-ABL1IS ratio <0.1%; deep molecular response (MR4.0): BCR-ABL1IS ratio <0.01% with >10,000 ABL1 copies; failure and suboptimal response: according to 2009 European LeukemiaNet (ELN) criteria; progression: transformation to advanced phases according to ELN criteria; leukemia-related death (LRD): death after progression. Results. Median age was 60 years at diagnosis and 64 years at last contact, with a median follow up of 48 months (range 2-86 months). High risk patients according to Sokal score and new EUTOS long-term survival (ELTS) score were 23% and 18%, respectively. A switch from imatinib to a second generation TKI was reported in 14% of patients for side-effects, and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The median time to switch was 8 months for toxicity and 20 months for failure. At 12 months, 55% of all evaluable patients were in MR3.0 or better. At last contact, 75% of all evaluable patients were in MR3.0 or better and 48% were in MR4.0 or better. The molecular response of patients switching for failure or suboptimal response was evaluable in 61/63 patients: improved in 57%, not modified in 38%, worsened by at least 1 log in 5% of patients. Overall, the treatment switch was associated with a remarkable increase of MR3.0 rate: from 10% at the time of switching to 52% at last qPCR. Overall, 33% achieved a stable MR4.0, of whom 22% with imatinib alone, and 11% after switching to a second generation TKI (Table 1). The 5-year overall survival (OS) and leukemia-related survival (LRS) were 85% and 93%, respectively. Twenty-seven patients (11%) died, of whom 13 (6%) of leukemia, after disease progression and 14 (6%) of "other" causes, without any evidence of progression. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients who received nilotinib in second-line. OS was not affected by age in the interval between 18 and 69 years (5-year OS 92%, ranging from 89% to 95 % in the different decades), but 5-year OS probabilities of elderly (70-79 years) and very elderly patients (≥ 80 years) were significantly lower (78%, P = 0.003, and 34%, P < 0.0001, respectively). The probability of LRS was not affected by age. The Sokal score predicted OS, but not LRS. The ELTS score clearly separated low, intermediate, and high risk patients for OS and also for LRS. Conclusions. The results of this prospective population-based study emphasize the importance of second-line treatment in the clinical practice: the CML management with the 3 available TKIs in the period 2008-2012, according to current treatment recommendations for switching and without any predefined obligation, resulted in response rates and outcomes, that are in the high range of prospective interventional studies investigating the efficacy and the safety of a single TKI in selected patients. This study provides a robust dataset on the results of CML treatment with TKI in clinical practice, that will be important for interpreting and evaluating the results of the next prospective studies, arguably limited to selected patients. Disclosures Castagnetti: Bristol-Myers Squibb: Consultancy, Honoraria; ARIAD Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Gugliotta:Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Marasca:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Roche: Honoraria. Soverini:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Ariad: Consultancy. Martinelli:Genentech: Consultancy; ARIAD: Consultancy; Roche: Consultancy; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; MSD: Consultancy; Pfizer: Consultancy, Speakers Bureau; Amgen: Consultancy. Cavo:Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Rosti:Novartis: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau. Baccarani:Ariad: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau.
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Risqiani, Renny, and Ari Mulianta Ginting. "Factors Influencing the Consumer’s Decision Using Financial Technology: Case Study in Jakarta." Jurnal Ekonomi dan Kebijakan Publik 13, no. 1 (July 18, 2022): 29–41. http://dx.doi.org/10.22212/jekp.v13i1.1980.
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Economic evolution started with the first wave of the industrial revolution. Economic evolution brought about changes in the economy. One of these effects is the advancement of technology, which has increased the use of Financial Technology (Fintech) in Indonesia. Fintech usage has risen in Indonesia, particularly in Jakarta. The study’s goal is to look at the elements that influence people’s decision to keep using fintech services. The study used non-probability sampling methods to obtain data from fintech users in Jakarta aged 17 to 35 years old over the research period of March to May 2020. The data was analyzed by using Structural Equation Model (SEM) with the AMOS software program. This study found that competitive pressures in technology services and the ease of digital technology offer consumers a wide range of options. Customers easily switch to other technology services at a reasonably affordable price. The study also found that variable consumer perceptions of benefits and trust variables in fintech services influence consumer attitudes. However, these two variables have no direct effect on the desire to continue using fintech services. Variable risk perception does not affect the attitude and desire of consumers to continue using fintech services. Variable attitudes affect the desire to continue using fintech services. The study results showed that increasing the penetration of fintech and continue consumers to continue to use fintech. It is necessary to improve risk perception to fintech used by consumers.Keywords: fintech, benefit and risk perception, Structural Equation Model AbstrakPerkembangan evolusi perekonomian dimulai dari gelombang pertama hingga masuk revolusi industri membawa perubahan terhadap perekonomian. Salah satu dampak tersebut adalah semakin berkembangnya teknologi. Perkembangan teknologi membawa dampak terhadap peningkatan Financial Technology (Fintech) di Indonesia. Penggunaan fintech di Indonesia mengalami peningkatan khususnya penggunaan fintech di Jakarta. Penelitian ini bertujuan untuk menganalisis faktor-faktor yang memengaruhi niat untuk terus memanfaatkan layanan fintech. Studi ini mengumpulkan data dari pengguna fintech di Jakarta yang berusia 17 hingga 35 tahun menggunakan metode non-probability sampling dengan periode penelitian dari bulan Maret – Mei tahun 2020. Analisis data menggunakan Structural Equation Model (SEM) dengan program software AMOS. Studi ini menemukan bahwa tekanan persaingan dalam layanan teknologi dan kemudahan teknologi digital menawarkan konsumen berbagai pilihan. Konsumen dengan mudah beralih ke layanan teknologi lain dengan harga yang cukup terjangkau. Penelitian ini juga menemukan bahwa variabel persepsi konsumen terhadap manfaat dan variabel kepercayaan terhadap layanan fintech berpengaruh terhadap sikap konsumen. Namun, kedua variabel tersebut tidak berpengaruh langsung terhadap keinginan untuk terus menggunakan layanan fintech. Variabel persepsi risiko tidak memengaruhi sikap dan keinginan konsumen untuk tetap menggunakan layanan fintech. Variabel sikap memengaruhi keinginan untuk terus menggunakan layanan fintech. Hasil studi menunjukkan bahwa penetrasi fintech meningkat dan konsumen terus menggunakan fintech. Persepsi risiko terhadap fintech yang digunakan konsumen perlu ditingkatkan.Kata kunci: fintech, manfaat dan persepsi risiko, Structural Equation Model
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Skrzypczak, Izabela. "Statistical Quality Inspection Methodology in Production of Precast Concrete Elements." Materials 16, no. 1 (January 2, 2023): 431. http://dx.doi.org/10.3390/ma16010431.
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Today, prefabricated concrete elements are used in many construction areas, including in industrial, public, and residential construction; this was confirmed via questionnaire research. In the article, the prospects for precast concrete development are presented, and the factors determining the use of this technology are defined. Based on a review of the literature, it was shown that currently, higher-quality prefabricated elements are primarily created through the implementation of innovative materials and production technologies. For this reason, the lack of research regarding quality control in prefabricated elements based on statistical quality control is particularly noticeable. The quality control process is one of the most important distinguishing features in prefabrication due to the increasingly stringent expectations of customers; it helps to ensure that the desired durability of implemented constructions is achieved. Issues related to assessing the effectiveness of standard procedures presented in this paper were analyzed using statistical methods in the form of OC (operating characteristic) and AOQ (average outgoing quality) curves. Thus, a new approach was proposed because these methods have not been previously used in precast concrete. The shape of the curves obtained confirmed the significant dependence of the value of the acceptance probability on the defectiveness of production. In AQL control systems based on OC and AOQ curves, it is necessary to calculate the current average defectiveness, which should be treated as a basis for the decision to switch from one type of control (normal, tightened, or reduced) to another. In this respect, the standard requirements of quality control have been simplified, and it has not been considered necessary to determine the average defectiveness value in production processes. The examples included in this study, including the analysis of curb production data, clearly show the harmful effects of ignoring the actual process defectiveness. As a result of the calculations, it was found that the average actual defectiveness of the curbs produced could not be equated with batch defectiveness. The analyses carried out in this study prove that equating batch defectiveness with process defectiveness is not an appropriate approach, which was confirmed through the producer’s/customer’s risk analysis. The approach proposed in this study, the analysis of OC and AOQ curves, is an innovative solution in prefabrication and can be an effective tool for managing the quality of prefabricated products, taking into account economic boundary conditions.
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Luna, Alejandro, Natalia Estrada, Concepcion Boque, Blanca Xicoy, Pilar Giraldo, Anna Angona, Alberto Alvarez-Larrán, et al. "Safety and Efficacy Profile of Asciminib As Treatment in Chronic Myeloid Leukemia Patients after Several Tyrosine-Kinase Inhibitors Failure." Blood 136, Supplement 1 (November 5, 2020): 49–50. http://dx.doi.org/10.1182/blood-2020-138690.
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Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.
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Hirschberg, Birgit, James Maylie, John P. Adelman, and Neil V. Marrion. "Gating of Recombinant Small-Conductance Ca-activated K+ Channels by Calcium." Journal of General Physiology 111, no. 4 (April 1, 1998): 565–81. http://dx.doi.org/10.1085/jgp.111.4.565.
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Small-conductance Ca-activated K+ channels play an important role in modulating excitability in many cell types. These channels are activated by submicromolar concentrations of intracellular Ca2+, but little is known about the gating kinetics upon activation by Ca2+. In this study, single channel currents were recorded from Xenopus oocytes expressing the apamin-sensitive clone rSK2. Channel activity was detectable in 0.2 μM Ca2+ and was maximal above 2 μM Ca2+. Analysis of stationary currents revealed two open times and three closed times, with only the longest closed time being Ca dependent, decreasing with increasing Ca2+ concentrations. In addition, elevated Ca2+ concentrations resulted in a larger percentage of long openings and short closures. Membrane voltage did not have significant effects on either open or closed times. The open probability was ∼0.6 in 1 μM free Ca2+. A lower open probability of ∼0.05 in 1 μM Ca2+ was also observed, and channels switched spontaneously between behaviors. The occurrence of these switches and the amount of time channels spent displaying high open probability behavior was Ca2+ dependent. The two behaviors shared many features including the open times and the short and intermediate closed times, but the low open probability behavior was characterized by a different, long Ca2+-dependent closed time in the range of hundreds of milliseconds to seconds. Small-conductance Ca- activated K+ channel gating was modeled by a gating scheme consisting of four closed and two open states. This model yielded a close representation of the single channel data and predicted a macroscopic activation time course similar to that observed upon fast application of Ca2+ to excised inside-out patches.
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Falch, Torberg. "Teacher Mobility Responses to Wage Changes: Evidence from a Quasi-Natural Experiment." American Economic Review 101, no. 3 (May 1, 2011): 460–65. http://dx.doi.org/10.1257/aer.101.3.460.
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This paper utilizes a Norwegian experiment with exogenous wage changes to study teachers' turnover decisions. Within a completely centralized wage setting system, teachers in schools with a high degree of teacher vacancies in the past got a wage premium of about 10 percent during the period 1993–94 to 2002–03. The empirical strategy exploits that several schools switched status during the empirical period. In a fixed effects framework, I find that the wage premium reduces the probability of voluntary quits by six percentage points, which implies a short run labor supply elasticity of about 1¼.