Artykuły w czasopismach: „Custodum ss”

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Cheng, Ya-Wen, Anthony R. Anzell, Stefanie A. Morosky, Tristin A. Schwartze, Cynthia S. Hinck, Andrew P. Hinck, Beth L. Roman i Lance A. Davidson. "Shear Stress and Sub-Femtomolar Levels of Ligand Synergize to Activate ALK1 Signaling in Endothelial Cells". Cells 13, nr 3 (5.02.2024): 285. http://dx.doi.org/10.3390/cells13030285.

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Endothelial cells (ECs) respond to concurrent stimulation by biochemical factors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development. However, the mechanistic underpinnings of ALK1 signaling modulation by fluid flow and the link to AVMs remain uncertain. We recorded EC responses under varying SS magnitudes and ALK1 ligand concentrations by assaying pSMAD1/5/9 nuclear localization using a custom multi-SS microfluidic device and a custom image analysis pipeline. We extended the previously reported synergy between SS and BMP9 to include BMP10 and BMP9/10. Moreover, we demonstrated that this synergy is effective even at extremely low SS magnitudes (0.4 dyn/cm2) and ALK1 ligand range (femtogram/mL). The synergistic response to ALK1 ligands and SS requires the kinase activity of ALK1. Moreover, ALK1’s basal activity and response to minimal ligand levels depend on endocytosis, distinct from cell–cell junctions, cytoskeleton-mediated mechanosensing, or cholesterol-enriched microdomains. However, an in-depth analysis of ALK1 receptor trafficking’s molecular mechanisms requires further investigation.

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Nakamori, Kenji, Manabu Yamagishi, Keigo Takaya, Tomohiro Igarashi i Hiroyoshi Hiratsuka. "Effectiveness of a Custom-Made Temporary Obturator after Bilateral Total Maxillectomy". Surgical Science 04, nr 07 (2013): 322–24. http://dx.doi.org/10.4236/ss.2013.47063.

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Ragonezi, Carla, Nuno Nunes, Maria Cristina O. Oliveira, José G. R. de Freitas, José Filipe T. Ganança i Miguel Â. A. Pinheiro de Carvalho. "Sewage Sludge Fertilization—A Case Study of Sweet Potato Yield and Heavy Metal Accumulation". Agronomy 12, nr 8 (13.08.2022): 1902. http://dx.doi.org/10.3390/agronomy12081902.

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Sewage sludge (SS) is derived from wastewater treatment plants and can be used as a biofertilizer when properly stabilized. This work aimed to evaluate SS application for agricultural production improvement. SS was tested on Porto Santo Island (Portugal). The experiment was randomly designed with three 25 m2 plots for each treatment (2 SS concentrations + control without SS) and performed in two consecutive cycles. For the first cycle, dehydrated sludge was mixed with soil, obtaining final concentrations of 0.8 kg/m2 (C1) and 1.6 kg/m2 (C2). Half of the concentration was used for the second cycle. Fifty-eight sweet potato plants were used in each plot. SS application boosted the agronomic parameters of biomass, productivity, and shoot biomass. Furthermore, improvements in soil properties were observed, mainly for pH, CEC, and NO3-N, with no significant increase in heavy metals. For the edible parts, heavy metal concentrations decreased, and Pb was the only one that still exceeded the maximum limits. The results demonstrated that SS application to low-fertility soil is effective in improving the agronomic parameters of sweet potato and enhancing soil features. Further studies considering other variables, i.e., SS origin, soil properties, and the crop, must be carried out to propose custom applications.

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Salehpour, F., Z. Ghanian, C. Yang, N. N. Zheleznova, T. Kurth, R. K. Dash, A. W. Cowley i M. Ranji. "Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging". American Journal of Physiology-Renal Physiology 309, nr 4 (15.08.2015): F377—F382. http://dx.doi.org/10.1152/ajprenal.00098.2015.

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The goal of the present study was to quantify and correlate the contribution of the cytosolic p67 phox subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67 phox was rendered functionally inactive by zinc finger nuclease mutation of the gene (SSp67 phox-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly ( P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SSp67 phox-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios ( P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SSp67 phox-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SSp67 phox rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67 phox subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat.

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Resnik, Matic, Metka Benčina, Eva Levičnik, Niharika Rawat, Aleš Iglič i Ita Junkar. "Strategies for Improving Antimicrobial Properties of Stainless Steel". Materials 13, nr 13 (30.06.2020): 2944. http://dx.doi.org/10.3390/ma13132944.

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In this review, strategies for improving the antimicrobial properties of stainless steel (SS) are presented. The main focus given is to present current strategies for surface modification of SS, which alter surface characteristics in terms of surface chemistry, topography and wettability/surface charge, without influencing the bulk attributes of the material. As SS exhibits excellent mechanical properties and satisfactory biocompatibility, it is one of the most frequently used materials in medical applications. It is widely used as a material for fabricating orthopedic prosthesis, cardiovascular stents/valves and recently also for three dimensional (3D) printing of custom made implants. Despite its good mechanical properties, SS lacks desired biofunctionality, which makes it prone to bacterial adhesion and biofilm formation. Due to increased resistance of bacteria to antibiotics, it is imperative to achieve antibacterial properties of implants. Thus, many different approaches were proposed and are discussed herein. Emphasis is given on novel approaches based on treatment with highly reactive plasma, which may alter SS topography, chemistry and wettability under appropriate treatment conditions. This review aims to present and critically discuss different approaches and propose novel possibilities for surface modification of SS by using highly reactive gaseous plasma in order to obtain a desired biological response.

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Sztafrowski, Edward. "Przepisy kanoniczne dotyczące przechowywania Eucharystii". Prawo Kanoniczne 31, nr 1-2 (5.06.1988): 31–41. http://dx.doi.org/10.21697/pk.1988.31.1-2.03.

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Mense Iunio 1987 a. Congressus E ucharisticus Nationalis in Polonia — praesente Papa Joanne Paulo — celebrabitur. Hac de de causa in Facultate luris Canonici Academiae Theologiae Catholicae Varsoviae Canonistae Poloniae congregati sunt. Hoc in symposione nonnulae quaestiones ad Mysterium Ss. mae Eucharistiae pertinentes consideratae sunt. Inter alias etiam praelectio De custodia Ss. mae Eucharistiae in iure canonico habita est. Nunc autem uti articulus in hoc periodico inseritur. Auctor nunc vigentes normae canonicae hac in materia praesetare sibi porposuit. Cum autem , ut normae istae bene intelligi et interpretari possint, in luce principiorum theologicorum considerandae sunt, etiam doctrinae Concilii Vaticani II circa mystarium Eucharisticum breviter hic praesentatur. Eadem de causa nonnullae normae liturgicae proponuntur. In principio aspectus historicus illustratur.

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Kumarasamy, Sivarajan, Harshal Waghulde, Xi Cheng, Steven T. Haller, Blair Mell, Basrur Abhijith, Usman M. Ashraf, Ealla Atari i Bina Joe. "Targeted disruption of regulated endocrine-specific protein (Resp18) in Dahl SS/Mcw rats aggravates salt-induced hypertension and renal injury". Physiological Genomics 50, nr 5 (1.05.2018): 369–75. http://dx.doi.org/10.1152/physiolgenomics.00008.2018.

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Hypertension is a classic example of a complex polygenic trait, impacted by quantitative trait loci (QTL) containing candidate genes thought to be responsible for blood pressure (BP) control in mammals. One such mapped locus is on rat chromosome 9, wherein the proof for a positional candidate gene, regulated endocrine-specific protein-18 ( Resp18) is currently inadequate. To ascertain the status of Resp18 as a BP QTL, a custom targeted gene disruption model of Resp18 was developed on the Dahl salt-sensitive (SS) background. As a result of this zinc-finger nuclease (ZFN)-mediated disruption, a 7 bp deletion occurred within exon 3 of the Resp18 locus. Targeted disruption of Resp18 gene locus in SS rats decreases its gene expression in both heart and kidney tissues regardless of their dietary salt level. Under a high-salt dietary regimen, both systolic and diastolic BP of Resp18mutant rats were significantly increased compared with SS rats. Resp18mutant rats demonstrated increased renal damage, as evidenced by higher proteinuria and increased renal fibrosis compared with SS rats. Furthermore, under a high-salt diet regimen, the mean survival time of Resp18mutant rats was significantly reduced compared with SS rats. These findings serve as evidence in support of Resp18 as a gene associated with the development of hypertension and renal disease.

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KEDARISETTI, KANAKA DURGA, MARCIN J. MIZIANTY, SCOTT DICK i LUKASZ KURGAN. "IMPROVED SEQUENCE-BASED PREDICTION OF STRAND RESIDUES". Journal of Bioinformatics and Computational Biology 09, nr 01 (luty 2011): 67–89. http://dx.doi.org/10.1142/s0219720011005355.

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Accurate identification of strand residues aids prediction and analysis of numerous structural and functional aspects of proteins. We propose a sequence-based predictor, BETArPRED, which improves prediction of strand residues and β-strand segments. BETArPRED uses a novel design that accepts strand residues predicted by SSpro and predicts the remaining positions utilizing a logistic regression classifier with nine custom-designed features. These are derived from the primary sequence, the secondary structure (SS) predicted by SSpro, PSIPRED and SPINE, and residue depth as predicted by RDpred. Our features utilize certain local (window-based) patterns in the predicted SS and combine information about the predicted SS and residue depth. BETArPRED is evaluated on 432 sequences that share low identity with the training chains, and on the CASP8 dataset. We compare BETArPRED with seven modern SS predictors, and the top-performing automated structure predictor in CASP8, the ZHANG-server. BETArPRED provides statistically significant improvements over each of the SS predictors; it improves prediction of strand residues and β-strands, and it finds β-strands that were missed by the other methods. When compared with the ZHANG-server, we improve predictions of strand segments and predict more actual strand residues, while the other predictor achieves higher rate of correct strand residue predictions when under-predicting them.

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Alnashawy, Ayed Salem. "Approval of the text and its legal applications". April 2022 Issue 11, nr 2 (1.03.2022): 62–81. http://dx.doi.org/10.25255/ss.2022.11.2.62.81.

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The study showed the concept of approval, linguistically and idiomatically, and then the types of approval. It is the desirability of the text (the effect), the desirability of consensus, the desirability of custom or habit, the desirability of necessity, and the desirability of analogy. Approval or is it a matter of establishing the ruling with evidence and not approving, the result of the study was that approbation of the text (the effect) is not considered approbation in the idiomatic sense known to scholars of origins, but rather it is a ruling proven by evidence from the book or Sunnah, taking into account the honorable law for the benefit of the people, and the evidence is not approbation In its fundamentalist sense, which is based on the diligence of the mujtahid in what is not stipulated in the text, it is an act of pure evidence.

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Mackenbrock, Lars H. B., Grzegorz Łabuz, Timur M. Yildirim, Gerd U. Auffarth i Ramin Khoramnia. "Automatic Quantitative Assessment of Lens Opacities Using Two Anterior Segment Imaging Techniques: Correlation with Functional and Surgical Metrics". Diagnostics 12, nr 10 (4.10.2022): 2406. http://dx.doi.org/10.3390/diagnostics12102406.

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The purpose of this study is to quantitatively assess lens opacity, using a swept-source optical coherence tomography (SS-OCT) device for anterior segment assessment, and establish the correlation with Scheimpflug imaging, corrected distance visual acuity (CDVA) and cumulative dissipated energy (CDE). This prospective cross-sectional single-center study enrolled 51 patients (51 eyes) with crystalline lens opacity. Patients with previous ocular surgery, pathologies or general disorders affecting vision were excluded. Eyes were scanned with an SS-OCT device, and lens densitometry was automatically analyzed using a custom MATLAB script which examined lens density, nuclear density and linear density. The same analyses were performed on Scheimpflug images. Preoperative CDVA and CDE during phacoemulsification were recorded. Spearman’s (ρ) and Pearson’s (r) correlation coefficients were assessed according to data normality. Statistically significant correlations were established between SS-OCT and Scheimpflug imaging using lens analysis (ρ = 0.47, p < 0.001), nuclear analysis (ρ = 0.73, p < 0.001) and linear analysis (r = 0.44, p < 0.001). A significant correlation with CDE was found with all the SS-OCT methods (r = 0.57, p < 0.001). Only the nuclear analysis of the SS-OCT scans (Tb = −0.33, p < 0.01) and Pentacam Nucleus Staging (Tb = −0.26, p < 0.05) showed a statistically significant correlation with CDVA. Good inter-device agreement in lens densitometry was found. However, SS-OCT yielded improved lens imaging compared with the Scheimpflug device and a higher correlation with clinical parameters. Thus, high-resolution SS-OCT has the potential to become a preferable option for automatic cataract grading and preoperative planning.

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Chapman, Michael G., Megna N. Shah, Sean P. Donegan, J. Michael Scott, Paul A. Shade, David Menasche i Michael D. Uchic. "AFRL Additive Manufacturing Modeling Series: Challenge 4, 3D Reconstruction of an IN625 High-Energy Diffraction Microscopy Sample Using Multi-modal Serial Sectioning". Integrating Materials and Manufacturing Innovation 10, nr 2 (czerwiec 2021): 129–41. http://dx.doi.org/10.1007/s40192-021-00212-9.

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AbstractHigh-energy diffraction microscopy (HEDM) in-situ mechanical testing experiments offer unique insight into the evolving deformation state within polycrystalline materials. These experiments rely on a sophisticated analysis of the diffraction data to instantiate a 3D reconstruction of grains and other microstructural features associated with the test volume. For microstructures of engineering alloys that are highly twinned and contain numerous features around the estimated spatial resolution of HEDM reconstructions, the accuracy of the reconstructed microstructure is not known. In this study, we address this uncertainty by characterizing the same HEDM sample volume using destructive serial sectioning (SS) that has higher spatial resolution. The SS experiment was performed on an Inconel 625 alloy sample that had undergone HEDM in-situ mechanical testing to a small amount of plastic strain (~ 0.7%), which was part of the Air Force Research Laboratory Additive Manufacturing (AM) Modeling Series. A custom-built automated multi-modal SS system was used to characterize the entire test volume, with a spatial resolution of approximately 1 µm. Epi-illumination optical microscopy images, backscattered electron images, and electron backscattered diffraction maps were collected on every section. All three data modes were utilized and custom data fusion protocols were developed for 3D reconstruction of the test volume. The grain data were homogenized and downsampled to 2 µm as input for Challenge 4 of the AM Modeling Series, which is available at the Materials Data Facility repository.

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Moleko-Boyce, Pulleng, Hlamulo Makelane, Mbokazi Z. Ngayeka i Zenixole R. Tshentu. "Recovery of Platinum Group Metals from Leach Solutions of Spent Catalytic Converters Using Custom-Made Resins". Minerals 12, nr 3 (16.03.2022): 361. http://dx.doi.org/10.3390/min12030361.

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Platinum group metals (PGMs) play a key role in modern society as they find application in clean technologies and other high-tech equipment. Spent catalytic converters as a secondary resource contain higher PGM concentrations and the recovery of these metals via leaching is continuously being improved but efforts are also directed at the purification of individual metal ions. The study presents the recovery of PGMs, namely, rhodium (Rh), platinum (Pt) and palladium (Pd) as well as base metals, namely, zinc (Zn), nickel (Ni), iron (Fe), manganese (Mn) and chromium (Cr) using leachates from spent diesel and petrol catalytic converters. The largest amount of Pt was leached from the diesel catalytic converter while the petrol gave the highest amount of Pd when leached with aqua regia. Merrifield beads (M) were functionalized with triethylenetetramine (TETA), ethane-1,2-dithiol (SS) and bis((1H-benzimidazol-2-yl)methyl)sulfide (NSN) to form M-TETA, M-SS and M-NSN, respectively, for recovery of PGMs and base metals from the leach solutions. The adsorption and loading capacities of the PGMs and base metals were investigated using column studies at 1 M HCl concentration. The loading capacity was observed in the increasing order of Pd to be 64.93 mmol/g (M-SS), 177.07 mmol/g (M-NSN), and 192.0 mmol/g (M-TETA), respectively, from a petrol catalytic converter. The M-NSN beads also had a much higher loading capacity for Fe (489.55 mmol/g) compared to other base metals. The finding showed that functionalized Merrifield resins were effective for the simultaneous recovery of PGMs and base metals from spent catalytic converters.

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Horvai, Andrew E., Miranda J. Kramer i Richard O'Donnell. "β-Catenin Nuclear Expression Correlates With Cyclin D1 Expression in Primary and Metastatic Synovial Sarcoma: A Tissue Microarray Study". Archives of Pathology & Laboratory Medicine 130, nr 6 (1.06.2006): 792–98. http://dx.doi.org/10.5858/2006-130-792-cnecwc.

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Abstract Context.—The association between aberrant (nuclear) β-catenin expression and cyclin D1 accumulation has been demonstrated in diverse neoplasms. In synovial sarcoma (SS), aberrant β-catenin expression has prognostic relevance, but the association with cyclin D1 has not been established. The SYT-SSX fusion protein, unique to SS, may independently increase cyclin D1. Objective.—To determine whether nuclear β-catenin is associated with cyclin D1 overexpression in SS and whether primary and metastatic SS differ in the expression of these markers. Design.—We incorporated 82 tumors initially diagnosed as SS into a tissue array. Fluorescence in situ hybridization with custom probes was used to select t(X;18) positive tumors. Clinical data, tumor type and outcome were tabulated. The tumors were tested for the association between nuclear β-catenin and cyclin D1 immunostaining. Primary and metastatic tumors were compared. Results.—Fifty-one tumors (41 primary and 10 metastatic) from 43 patients demonstrated t(X;18). Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear β-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively. No significant difference was noted between primary and metastatic tumors with respect to the above markers. The presence of nuclear β-catenin showed a significant association with cyclin D1 expression (P < .001). A small number of cyclin D1 cases were negative for nuclear β-catenin but positive for phosphorylated Akt. Conclusions.—Increased cyclin D1 in SS may be driven by abnormally expressed β-catenin, similar to other neoplasms. The pattern of expression of these markers is established early during tumorigenesis.

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Riedel, Richard, Robin Jones, Antoine Italiano, Chet Bohac, Juliette Thompson, Kerstin Mueller, Zaeem Khan, Seth Pollack i Brian Van Tine. "Systemic Anti-Cancer Therapy in Synovial Sarcoma: A Systematic Review". Cancers 10, nr 11 (1.11.2018): 417. http://dx.doi.org/10.3390/cancers10110417.

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Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.

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Marcin, Michal, Martin Sisol, Dušan Kudelas, Igor Ďuriška i Tomáš Holub. "The Differences in Evaluation of Flotation Kinetics of Talc Ore Using Statistical Analysis and Response Surface Methodology". Minerals 10, nr 11 (11.11.2020): 1003. http://dx.doi.org/10.3390/min10111003.

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This paper investigates the effect of sodium hexametaphosphate (SHMP) depressant/dispersant in the presence of methyl isobutyl carbinol (MIBC) frother and soluble starch (SS) depressant on the flotation kinetics of talc ore. Emphasis is on a comparison between the evaluation of a custom design of experiment (DoE) using the multilinear regression analysis (MRA) and response surface methodology (RSM) approach. Although analysis of variance (ANOVA) is a good first step in the evaluation of the effect of factors on froth flotation processing, it nonetheless only reveals the effects that are the same under all conditions. In the case of SHMP, its effect on separation efficiency is positive; however, if it is used along with SS, the effect is negative. Moreover, if a higher frother dosage is used, the effect of SHMP on separation efficiency is negligible.

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Pliska, Benjamin T., John P. Beyer i Brent E. Larson. "A comparison of resistance to sliding of self-ligating brackets under an increasing applied moment". Angle Orthodontist 81, nr 5 (14.05.2011): 794–99. http://dx.doi.org/10.2319/111510-666.1.

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Abstract Objective: To test the null hypotheses that at clinically relevant amounts of applied moment, there are no differences in the amount of resistance to sliding (RS) between self-ligating (SL) and conventionally ligated (CL) brackets on both stainless steel (SS) and nickel-titanium (NT) archwire. Materials and Methods: Three different SL brackets and one CL bracket, all 0.022″ slot, were tested on a custom-built device to simulate canine retraction mechanics in the second-order dimension. The setup allowed for simultaneous and continuous measurement of RS and applied moment at the bracket-archwire interface. The brackets tested were Damon3, In-Ovation R, Smartclip, and Victory, all of which were tested with 0.019″ × 0.025″ SS and NT archwires. The RS at calculated moments of 2000 g-mm and 4000 g-mm was determined and compared between the various brackets and both archwire types. Descriptive measures, analysis of variance, and Tukey-Kramer post-test comparisons were used to calculate results. Results: All brackets displayed a greater amount of RS with NT than with SS archwires. At the higher moment levels (4000 g-mm), no significant reduction in RS was found between CL and SL brackets on both SS and NT archwires. At lower levels of applied moment (2000 g-mm), reductions in RS of 18% (42.7 g) and 18% (38.5 g) were found between the CL bracket and the best performing SL bracket on NT and SS, respectively. Conclusion: At low values of applied moment, some statistical differences were found; however, in general, the differences in RS amongst the various SL and CL brackets tested may not be clinically relevant.

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Rybalko, Danil, Aimee Bobko, Farid Amirouche, Dmitriy Peresada, Awais Hussain, Michael Patetta, Anshum Sood, Jason Koh i Benjamin Goldberg. "Biomechanics in an Incomplete Versus Complete Supraspinatus Tear: A Cadaveric Study". Orthopaedic Journal of Sports Medicine 8, nr 12 (1.12.2020): 232596712096447. http://dx.doi.org/10.1177/2325967120964476.

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Background: Degenerative and traumatic changes to the rotator cuff can result in massive and irreparable rotator cuff tears (RCTs). Purpose/Hypothesis: The study objective was to conduct a biomechanical comparison between a small, incomplete RCT and a large, complete RCT. We hypothesized that the incomplete supraspinatus (SS) tear would lead to an incremental loss of abduction force and preserve vertical position of the humeral head, while a complete SS tear would cause superior humeral migration, decrease functional deltoid abduction force, and increase passive range of motion (ROM). Study Design: Controlled laboratory study. Methods: Six cadaveric shoulders were evaluated using a custom testing apparatus. Each shoulder was subjected to 3 conditions: (1) intact/control, (2) 50%, full-thickness, incomplete SS tear, and (3) 100%, complete SS tear. Deltoid abduction force, superior humeral head migration, and passive ROM were measured in static conditions at 0°, 30°, and 60° of glenohumeral abduction, respectively. Results: The intact SS resulted in a mean deltoid abduction force of 2.5, 3.3, and 3.8 N at 0°, 30°, and 60° of abduction, respectively. Compared with the intact shoulder, there was no significant difference in mean abduction force seen in the incomplete tear, while the force was significantly decreased by 52% at 30° of abduction in the complete tear ( P = .009). Compared with the incomplete tear, there were significant decreases in abduction force seen in the complete tear, by 33% and 48% (0.9 N and 1.1 N) at 0° and 30° of abduction, respectively ( P = .04 and .004). The intact configuration experienced a mean superior humeral head migration of 1.5, 1.4, and 1.1 mm at 0°, 30°, and 60° of abduction, respectively. The complete tear resulted in a superior migration of 3.0 and 4.4 mm greater than the intact configuration at 0° and 30° of abduction, respectively ( P = .001). There was a 5° and 10° increase in abduction ROM with 50% and 100% tears, respectively ( P = .003 and .03). Conclusion: An incomplete SS tear does not significantly alter the biomechanics of the shoulder, while a large, complete SS tear leads to a significant superior humeral migration, a decreased deltoid abduction force, and a mild increase in passive ROM. Clinical Relevance: Our findings demonstrate the effects of large SS tears on key biomechanical parameters, as they progress from partial tears.

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Seely, Kai, Shwetha Mangalesh, Katrina Winter, Vincent Tai, Du Tran-Viet, Stephanie Chiu i Cynthia Toth. "4431 Utilization of swept source optical coherence tomography to optimize characterization of cystoid macular edema in preterm infants". Journal of Clinical and Translational Science 4, s1 (czerwiec 2020): 103–4. http://dx.doi.org/10.1017/cts.2020.320.

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OBJECTIVES/GOALS: The goal of this study is to evaluate and optimize the characterization of cystoid macular edema (CME) using an investigational swept source (SS)-OCT system. Our knowledge of CME in preterm infants is limited; optimizing its characterization is a critical step in understanding its impact on vision. METHODS/STUDY POPULATION: In this IRB-approved protocol, 118 preterm infants were imaged in the Duke intensive care nursery (ICN) with a novel lightweight, hand-held, high-speed, SS-OCT system following routine clinical eye exams. SS-OCT images were deidentified, automatically segmented using custom software (DOCTRAP), measured for several retinal layer thicknesses, and reviewed by masked expert graders for the presence and severity of CME. Reliability of SS-OCT measures will be assessed, and the association between CME status and retinal layer thicknesses will be calculated using logistic regression modeling. RESULTS/ANTICIPATED RESULTS: The prevalence of CME overall and by severity will be calculated. The distribution of several retinal layer thicknesses will be reported and compared by infant CME status and, when edema is present, by CME severity. Reproducibility and repeatability will be reported for objective variables, and intra-grader and inter-grader agreement will be reported for subjective variables. Multivariate logistic regression coefficients and odds ratios will be calculated for each retinal layer thickness variable. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will use a novel SS-OCT system to identify retinal thickness measures that may be objective markers of CME status. This will refine the characterization of CME and provide a framework for correlating CME with functional outcomes like visual acuity. CONFLICT OF INTEREST DESCRIPTION: SC and CT have unlicensed patents on relevant technologies. CT receives royalties from Alcon and Hemosonics and consultation fees from EMMES.

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Mestre Navas, Pablo Alberto. "Imago ecclesiae: los sellos de validación de los cabildos catedrales de Baeza y Jaén (ss. XIII-XIV)". Espacio Tiempo y Forma. Serie III, Historia Medieval, nr 35 (18.04.2022): 443–74. http://dx.doi.org/10.5944/etfiii.35.2022.31238.

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La restauración eclesiástica en el reino de Jaén supuso la puesta en marcha de la institución capitular, que residiría en Baeza hasta su traslado a Jaén después de que se verificase su conquista, permaneciendo parte de los canónigos en la antigua catedral. La organización de este cabildo coincidió con la difusión que el sello de validación experimentó en los reinos peninsulares durante el siglo XIII. En este artículo se estudia la creación del sello capitular de Baeza-Jaén, su utilización como instrumento de garantía jurídica en la expedición de documentos y su custodia. A través de diversas improntas conservadas en el archivo capitular de Toledo, se analiza la evolución que experimentó la representación iconográfica del campo del sello, evidenciándose importantes modificaciones en el último tercio del siglo XIII.

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Batista, Graziela R., Alessandra B. Borges, Rayssa F. Zanatta, Cesar R. Pucci i Carlos R. G. Torres. "Esthetical Properties of Single-Shade and Multishade Composites in Posterior Teeth". International Journal of Dentistry 2023 (12.09.2023): 1–9. http://dx.doi.org/10.1155/2023/7783321.

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This study aimed to compare the aesthetic properties of posterior composite restorations made with a multishade (MS) or single-shade (SS) material. For that, 23 extracted human molars were used. The shade determination was performed, and the occlusal anatomy was registered by a custom-made stamp. Then, class I preparations were made, and each tooth was restored twice, using two different composites of MS/opacity layering material (Admira Fusion—Voco) and an SS/opacity bulk-fill composite (Admira Fusion X-tra—Voco). After finishing the first restoration with the MS material, a standardized picture was taken, and the restoration was removed. Then, the preparation was restored again with the other composite, obtaining a new picture. The pictures were randomly analyzed by 10 calibrated evaluators regarding color match using the FDI criteria. The evaluators were blinded to the restorative material used. Data were analyzed using an unpaired t-test and Wilcoxon test. The significance level adopted in the study was 5%. As a result, there were nonsignificant differences between the composites evaluated for color match, as well nonsignificant differences were obtained related to which restorative technique produced the best aesthetic results. Only for darker shades (A4, B4, and C4), most of the evaluators considered the restorations made with the MS material more aesthetic than with the SS, while for the other shades, nonsignificant differences were observed. Therefore, the choice of the SS and the MS/opacity composites does not influence the aesthetic outcome of posterior restorations for the lighter shades. However, the use of bulk fill material for dark shades is less favorable than the MS layering ones.

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Milenović, Živorad. "Educational activities and learning in the Lebensborn project of Nazi Germany". Zbornik radova Pedagoskog fakulteta, Uzice, nr 22 (2020): 121–30. http://dx.doi.org/10.5937/zrpfu2022121m.

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During the time of Nazi Germany from 1933 to 1945, that is, to the end of World War II, the most horrific crimes in human history took place. Nazi Germany was based on militarism, racism, anti-Semitism, ideologism and occultism. First, the Nuremberg Laws were passed, which led to the Holocaust, and on December 12, 1935, in Munich, by the order of the commander of the SS troops, Heinrich Himmler, a secret state Lebensborn project was established. The goal of this state project was to create a pure Aryan race, which was considered a key condition for Germany to become the world's leading power in military, economic and cultural terms, and for the German people to rule the world with their sublime tradition and culture. The Lebensborn project involved the birth of children from biological mothers carefully selected from the ranks of racially pure young, beautiful and healthy German girls and biological fathers from the ranks of SS troops, who would later be housed in Lebensborn homes or in the homes of SS officers or prominent purely Aryan families. Children abducted all over Europe, who met the criteria of seemingly belonging to the members of the pure Aryan race, were also accommodated in these homes. In addition to custody and upbringing, the educational activities and teaching of these children in Lebensborn homes were carried out under strict supervision, based on the principles of fascist pedagogy the point that will be discussed in this theoretical study.

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Mousavi, S. Mostafa, Charles A. Langston i Stephen P. Horton. "Automatic microseismic denoising and onset detection using the synchrosqueezed continuous wavelet transform". GEOPHYSICS 81, nr 4 (lipiec 2016): V341—V355. http://dx.doi.org/10.1190/geo2015-0598.1.

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Typical microseismic data recorded by surface arrays are characterized by low signal-to-noise ratios (S/Ns) and highly nonstationary noise that make it difficult to detect small events. Currently, array or crosscorrelation-based approaches are used to enhance the S/N prior to processing. We have developed an alternative approach for S/N improvement and simultaneous detection of microseismic events. The proposed method is based on the synchrosqueezed continuous wavelet transform (SS-CWT) and custom thresholding of single-channel data. The SS-CWT allows for the adaptive filtering of time- and frequency-varying noise as well as offering an improvement in resolution over the conventional wavelet transform. Simultaneously, the algorithm incorporates a detection procedure that uses the thresholded wavelet coefficients and detects an arrival as a local maxima in a characteristic function. The algorithm was tested using a synthetic signal and field microseismic data, and our results have been compared with conventional denoising and detection methods. This technique can remove a large part of the noise from small-amplitudes signal and detect events as well as estimate onset time.

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Baumhauer, J. F., R. Wervey, J. McWilliams, G. F. Harris i M. J. Shereff. "A Comparison Study of Plantar Foot Pressure in a Standardized Shoe, Total Contact Cast, and Prefabricated Pneumatic Walking Brace". Foot & Ankle International 18, nr 1 (styczeń 1997): 26–33. http://dx.doi.org/10.1177/107110079701800106.

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Total contact casting is the current recommended treatment for Wagner Stage 1 and 2 neuropathic plantar ulcers. The rationale for this treatment includes the equalization of plantar foot pressures and generalized unweighting of the foot through a total contact fit at the calf. Total contact casting requires meticulous technique and multiple cast applications to avoid complications before ulcer healing. An alternative to total contact casting is the use of a prefabricated brace designed to maintain a total contact fit. This study compares plantar foot pressure metrics in a standardized shoe (SS), total contact cast (TCC), and prefabricated pneumatic walking brace (PPWB). Five plantar foot sensors (Interlink Electronics, Santa Barbara, CA) were placed at the first, third, and fifth metatarsal heads, fifth metatarsal base, and midplantar heel of 10 healthy male subjects. Each subject walked at a constant speed over a distance of 280 meters in a SS, PPWB, and TCC. A custom-made portable microprocessor-based system, with demonstrated accuracy and reliability, was used to acquire the data. No significant differences in peak pressure or contact duration were found between the initial and repeat SS trials ( P > 0.05). Peak pressures were reduced in the PPWB as compared to the SS for all sensor locations ( P < 0.05). Similarly, peak pressures were reduced in the TCC compared to the SS for all sensor locations ( P < 0.05) with the exception of the fifth metatarsal base ( P = 0.45). Our results are summarized as follows: (1) the methods used in the current study were found to be reliable through a test-retest analysis; (2) the PPWB decreased peak plantar foot pressures to an equal or greater degree than the TCC in all tested locations of the forefoot, midfoot, and hindfoot; (3) compared to a SS, contact durations were increased in both the TCC and PPWB for most sensor locations; and (4) the relationship of peak pressure over time, the pressure-time integral, is lower in the brace compared to the shoe at the majority of sensor locations. The values are not significantly different between the cast and shoe. These findings suggest an unweighting of the plantar foot and equalization of plantar foot pressures with both the PPWB and TCC. Based on these findings, the PPWB may be useful in the treatment of neuropathic plantar ulcerations of the foot.

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Gollamudi, Jahnavi, Rowan Goldin, Paul Territo i Hyacinth Idu Hyacinth. "The Role of P-Selectin in Microvascular Hemodynamics and Cerebral Brain Volumes in Aging Sickle Cell Mice". Blood 142, Supplement 1 (28.11.2023): 2486. http://dx.doi.org/10.1182/blood-2023-189295.

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Cerebral vasculopathy has been linked to the development of cognitive impairment in sickle cell disease (SCD). We have previously demonstrated that 13-month-old sickle cell mice recapitulate features of cerebral vasculopathy such as tortuous vessels, microthrombi, and hypoperfusion seen in adults with SCD. Histologically, we also showed these mice have increased cerebral microvascular deposition of P-selectin and more frequent and larger microinfarcts compared to matched controls. We further showed that these mice developed evidence of cognitive deficit compared to matched controls. Based on these observations, we hypothesized P-selectin may play a critical role in development of cerebral micro vasculopathy and downstream pathologic sequalae such as microinfarcts by enhancing leukocyte-endothelial interactions. Furthermore, abundant evidence from non-sickle mice shows that microinfarcts can exacerbate small vessel changes including gray matter volume loss. Building on our prior work, in this study, we examined the effect of P-selectin deficiency on cerebral microvascular hemodynamics and leukocyte-endothelial interaction and well as changes in cortical and subcortical gray matter volume in aged sickle mice. Male, P-selectin knockout (Psel KO) or intact (Psel WT) chimeric mice were generated by transplanting control (AA) or sickle (SS) bone marrow into P-selectin knockout (Psel -/-) or C57BL/6 (B6) recipients. To assess the impact of vasculopathy and brain gray matter volume changes longitudinally, male mice were assessed at 12-, 14- or 16-month post-transplant. Hemodynamics (mean velocity, red blood cell (RBC) flux, white blood cell stalls in capillaries as well as venules) were obtained from line-scan images acquired using in-vivo two-photon microscopy, using custom and validated MATLAB scripts. Gray matter volumes in 26 cortical and subcortical brain regions with relevance to cognitive function, were derived from parcellation of T2-weighted magnetic resonance imaging after non-linear registration to Allen brain atlas T1 anatomical space. Parcellation was accomplished by registering the Paxinos atlas to the mouse T2 now in Allen space. Brain volume analyses was accomplished using Analyze 12 software. After the completion of in-vivo studies, brains were extracted for immunohistochemistry analysis. Statistical analysis was performed using two-way ANOVA. The breakdown of the mice included in this study are; 14 B6 AA, 12 B6 SS, 12 Psel KO AA and 13 Psel KO SS. Given the high attrition rate in older mice, data from 12-, 14- and 16-month-old cohorts were combined. Mean age of B6 AA cohort was 13.1 months, 12.8 months for B6 SS, 13. 9 months for Psel KO AA and 13.6 months for Psel KO SS mice and were not statistically different. Psel KO sickle mice had a significantly lower mean capillary RBC velocity (1.733 mm/s vs 4.717 mm/s, p < 0.01) compared to Psel WT SS mice. In addition, Psel KO SS mice had relatively smaller (more normal) capillary diameter compared to Psel WT SS mice (6.248 um vs 8.613 um, p < 0.001). Interestingly, there was no statistically significant difference in RBC flux between Psel KO SS and Psel WT SS mice, however Psel KO SS mice show a lower red blood cell flux similar to that seen in Psel WT AA mice ( Figure 1). Of the 26 brain regions that were assessed, Psel KO SS mice had larger measured gray matter volume in the frontal association cortex (3.01 ± 0.77 vs 3.66± 0.33 mm 3, p= 0.0083), prelimbic cortex (1.72 ± 0.27 vs 1.95 ± 0.17 mm 3, p=0.0079), hippocampus (17.67 ± 1.56 vs 16.21± 1.97 mm 3, p=0.01)( Figure 1) including other regions such as lateral (2.12 ± 0.19 vs 1.88 ± 0.31 vs mm 3 p=0.0096) medial (1.84± 0.16 vs 1.64 ± 0.26 mm 3, p=0.01), and ventral orbital cortex( 1.95± 0.17 vs1.72 ± 0.27 mm 3, p=0.01) and dorsolateral olfactory tract (1.46 6± 0.13 vs 1.31 ± 0.20 mm 3, p=0.023 compared to the Psel WT SS mice (data not shown). In conclusion, non-hematopoetic P-selectin deficiency improves cerebral vasculopathy as demonstrated by normalization of hemodynamics in sickle mice. We also show that Psel KO SS mice had larger brain gray matter volume in regions involved in cognitive function. Additional studies are needed to identify the underlying mechanism of improvement in brain gray matter volume as well as whether P-selectin could be potential target for reducing SCD associated neurological complications.

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Liang, Mingyu, Baozhi Yuan, Elizabeth Rute, Andrew S. Greene, Ai-Ping Zou, Paulo Soares, Gregory D. McQuestion, Glenn R. Slocum, Howard J. Jacob i Allen W. Cowley. "Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study". Physiological Genomics 8, nr 2 (28.02.2002): 139–49. http://dx.doi.org/10.1152/physiolgenomics.00083.2001.

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Substitution of chromosome 13 from Brown Norway BN/SsNHsd/Mcw (BN/Mcw) rats into the Dahl salt-sensitive SS/JrHsd/Mcw (SS/Mcw) rats resulted in substantial reduction of blood pressure salt sensitivity in this consomic rat strain designated SSBN13. In the present study, we attempted to identify genes associated with salt-sensitive hypertension by utilizing a custom, known-gene cDNA microarray to compare the mRNA expression profiles in the renal medulla (a tissue playing a pivotal role in long-term blood pressure regulation) of SS/Mcw and SSBN13 rats on either low-salt (0.4% NaCl) or high-salt (4% NaCl, 2 wk) diets. To increase the reliability of microarray data, we designed a four-way comparison experiment incorporating several levels of replication and developed a conservative yet robust data analysis method. Using this approach, from the 1,751 genes examined (representing more than 80% of all currently known rat genes), we identified 80 as being differentially expressed in at least 1 of the 4 comparisons. Substantial agreements were found between the microarray results and the results predicted on the basis of the four-way comparison as well as the results of Northern blots of 20 randomly selected genes. Analysis of the four-way comparison further indicated that ∼75% of the 80 differentially expressed genes were likely related to salt-sensitive hypertension. Many of these genes had not previously been recognized to be important in hypertension, whereas several genes/pathways known to be involved in hypertension were confirmed. These results should provide an informative source for designing future functional studies in salt-sensitive hypertension.

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Kayani, Saheeb Ahmed, Salman Sagheer Warsi i Raja Awais Liaqait. "A Smart Decision Support Framework for Sustainable and Resilient Supplier Selection and Order Allocation in the Pharmaceutical Industry". Sustainability 15, nr 7 (29.03.2023): 5962. http://dx.doi.org/10.3390/su15075962.

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Supplier selection and order allocation (SS-OA) are two of the most important strategic decisions for supply chain network design and operation. If sustainability and resilience criteria are taken into consideration together and a holistic sustainable and resilient SS-OA is carried out, it may enable the supply chain network to perform better when subjected to disruption scenarios. In this research paper, a novel comprehensive multi-phase, multi-period sustainable, and resilient SS-OA decision support framework has been proposed. This framework integrates fuzzy multi-criteria decision-making (MCDM) techniques with a fuzzy multi-objective mixed integer nonlinear programming (MOMINLP) mathematical model to optimize triple bottom line (TBL) sustainability and resilience criteria simultaneously for a multi-modal, multi-echelon supply chain network. The proposed framework has been implemented using real-time data collected from the pharmaceutical industry. The results show that among the TBL sustainability criteria, product price, past business, innovative capability, and information disclosure rank as the most significant sub-criteria for the DMs in the pharmaceutical industry, while robustness and flexibility are considered the most valued attributes for potential suppliers as far as the resilience criterion is concerned. An assessment of the results has revealed that transfer cost and custom clearance cost together comprise more than two-thirds of the overall cost of the supply chain network. It has also been noted that inland transportation of goods is dominated by rail as the most preferred mode of transport. Transportation by rail is particularly preferred by suppliers located in geographically contiguous countries.

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Fedorova, M. A. "M. W. Tofique, A. Löf, C. Millward, Z. Günther. Testing and calculation of impact fatigue strength of Flap-X and SS 716 flapper valve steel grades / trans from Engl. M. A. Fedorova". Omsk Scientific Bulletin. Series Aviation-Rocket and Power Engineering 5, nr 3 (2021): 63–74. http://dx.doi.org/10.25206/2588-0373-2021-5-3-63-74.

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During the operation of reciprocating compressors, the flapper valve opens and closes under fluid pressure and flow. As it closes, it strikes against the valve seat, generating stresses and noise. This cycle of loading produces bending and impact fatigue stresses in the reed. This load pattern is repeated billions of times during the service life of a compressor and it defines the service life and reliability. The goal of this study was to calculate the impact fatigue strength of the Flap-X and the SS 716 grades and, to provide the compressor manufacturers with the information they can use to specify a steel grade to be used in their compressors, for reliable service. Impact fatigue tests were conducted on a custom-built impact fatigue test rig that used air pulses to produce movement of the reed valves manufactured by a major European compressor manufacturer Nidec Global appliance GmbH, at a frequency of 315 Hz and pulse width of 2,2 milliseconds. The testing was conducted according to the staircase test method detailed in the International Standard SS-ISO 12107:2012. The impact fatigue strength of the Flap-X and SS 716 steel valves was calculated in terms of the impact velocity according to the modified staircase test method in the standard. The test results and their statistical analysis showed that the impact fatigue strength of the Flap-X grade was higher compared to the SS 716 grade. The calculation and testing of the impact fatigue strength of the flapper valve steel grades could help the compressor designers to select the optimum material for their compressor designs, to provide reliable service. The higher impact fatigue strength of the Flap-X grade, lower failure rate and longer impact fatigue life will allow the compressor manufacturers to design thinner valves, as Flap-X can sustain higher impact fatigue stresses reliably for longer time and, at the same time help reduce noise, as thinner valves produce less noise for a given pressure and frequency.

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Tejero, Eloy. "La sacramentalidad del matrimonio en la historia del pensamiento cristiano". Ius Canonicum 14, nr 27 (27.03.2018): 11–33. http://dx.doi.org/10.15581/016.14.21342.

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Adversus ulteriorem sacramentorum theologiam, quae sacramenti matrimonii considerationem firmare in e,fficatia intendet, SS. Patres admirabili copia symbolorum declarant matrimonii intimam societatem cum divino proposito salvandi. Ex hac perspectiva matrimonium simul est et mysterium et signum. Ab inicio Deus matrimonium secundum archetypum, quod Prius in intimitate sua custoditum posterius revelatum fuit, ordinavit. Ita mysterium matrimoniale originaliter convertitur in signo magni mysterii Christi sponsi Ecclesiae, simul ac Revelatio divina explicitatur et in Christo cons4/llmatur. Permansio matrimonii per diversas oeconomias salutis -quamvis ordo matrimonialis etiam patiatur diversos status quibus .homo possit inveniri- secum fert quod symbolismum matrimonii ut prophetia, vel typus, vel praefiguratio aut rememoratio magni mysterii Christi prospectum sit. Unitas qua SS. Patres duo contemplantur Testamenta explicat quod symbolismum sacramentorum proicietur per oeconomias salvlficas et quod in matrimonio assurgatur iam ab initio, etenim duobus primis hominibus iam fuit matrimonium, non yero cetera sacramenta. luxta character symbolicum, in doctrina Patrum eminet etiam alius aspectus sacramenti, qui incidit etiam in matrimonium. Significatio sacramenti romani obligationem ante divinitatem implicabat. Permansio huius significationis scriptis christianis, transformatae yero novitate christianismi, nullam post philologica studia thematis dubitationem. of,fert. In hoc sensu inspiciendum est quomodo fontes illius aetatis insistant in relatione matrimoniali configurata mysterio Christi. Matrimonium non est ductilis ad simplex pactum inter partes: custoditur in Christo et in Ecclesia. Ita apparet claraconvenientia inter symbolismum matrimonial e et naturam vinculi unionis sponsatorum.

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Zaman, Qamar Uz, Arnold Walter Schumann i David Charles Percival. "An Automated Cost-effective System for Real-time Slope Mapping in Commercial Wild Blueberry Fields". HortTechnology 20, nr 2 (kwiecień 2010): 431–37. http://dx.doi.org/10.21273/horttech.20.2.431.

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The development of site-specific agriculture has increased the need for knowledge regarding within-field variability in factors such as soil/plant characteristics and topography that influence wild blueberry (Vaccinium angustifolium) production. Surface soil properties are the first type of information most frequently used by blueberry producers in developing management plans. Topographic features are not yet routinely used to guide within-field management. The majority of blueberry fields in eastern Canada have gentle to severe topography. An automated slope measurement and mapping system (SMMS) consisting of low-cost accelerometers used as tilt sensors, differential global positioning system (DGPS), and laptop and custom software was developed. The SMMS was mounted on an all-terrain vehicle for real-time slope measurement and mapping. Six commercial wild blueberry fields were surveyed in central Nova Scotia to evaluate the performance of SMMS. The automatically sensed slopes (SS) were also compared with manually measured slopes (MS) at 20 randomly selected points in each field to examine the accuracy of SMMS. The SMMS measured slope reliably in the selected fields with root mean square error ranging from 0.12 to 0.56 degrees and correlations of SS with MS of R2 = 0.95 to 0.99. The selected fields had substantial variation in slope (ranging from 0.8 to 31.0 degrees). Therefore, the use of low-cost and reliable accelerometers with a DGPS is a better option than expensive real-time kinematic DGPS for developing cost-effective SMMS to quantify and map slopes (real-time) for planning site-specific management practices in commercial fields. The SS maps or real-time SMMS could also be used to adjust vehicle speed at particularly steep slopes.

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Avinash, CK Anulekha, Ramesh Nadiger i Sathyabodh S. Guttal. "Orbital Prosthesis: A Novel Treatment Approach". International Journal of Prosthodontics and Restorative Dentistry 2, nr 1 (2012): 19–23. http://dx.doi.org/10.5005/jp-journals-10019-1041.

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ABSTRACT The disfigurement associated with loss of eye can cause significant physical and emotional disturbance. Rehabilitation of facial defects is a complex task, requiring an individualized design of the technique for each patient and also a technique sensitive procedure, visual assessment alone may not be accurate. We report a case of 23-year-old male patient with rhabdomyosarcoma of the eye, which was treated with chemotherapy and surgical enucleation, and was rehabilitated with silicon orbital prosthesis by constructing a custom ocular prosthesis to achieve ideal fit and esthetics. How to cite this article Avinash CKA, Nadiger R, Guttal SS, Lekha K. Orbital Prosthesis: A Novel Treatment Approach. Int J Prosthodont Restor Dent 2012;2(1):19-23.

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Cao, Xinxin, Ming-hui Duan, Ai-lin Zhao, Hao Cai, Jia Chen, Xue-min Gao, Ting Liu i in. "Treatment Outcome and Prognostic Factors for Adult Langerhans Cell Histiocytosis". Blood 136, Supplement 1 (5.11.2020): 38. http://dx.doi.org/10.1182/blood-2020-138426.

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Background: The clinical features and prognosis of adult Langerhans cell histiocytosis (LCH) remained poorly defined. Although recurrent somatic activating mutations of BRAFV600E and additional genetic drivers of MAPK pathway had been discovered in LCH, most genomic analyses were from children and the spectrum of genetic alterations and the impact of these genetic mutations on clinical presentation in adult LCH remains elusive. To address these questions, we retrospectively studied the clinical features, organ involvement, treatment approaches, genomic analyses and outcomes of adult LCH patients in our center. Methods: Patients diagnosed with LCH between January 2001 and June 2020 at Peking Union Medical College Hospital were included in this retrospective study. BRAF or MAP2K1 mutation was detected by a custom-designed NGS panel. Patients were classified according to the number of systems involved: SS-s, one lesion in a single system; SS-m, multiple lesions within one single system; and MS, multiple systems involved. The overall survival (OS) was defined as the duration from the diagnosis of LCH to the date of death. The event free survival (EFS) was defined as the duration from the initiation of treatment for LCH to reactivation after treatment and death from any cause. Results: Overall 266 patients were enrolled, 177 patients were male (66.5%). The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 58 patients had SS-s LCH (21.8%), 26 patients had SS-m LCH with bone involvement (9.8%) and 182 patients had MS LCH (68.4%). The most common organ involved in MS patients was bone (69.8%), followed by the pituitary (61.5%), lung (61.0%), lymph nodes (35.2%), skin (26.4%), liver (23.1%), thyroid (13.7%), spleen (8.2%), CNS (3.8%) and gastrointestinal tract (1.1%). No patients had hematopoietic system involvement. For 67 patients, BRAF and MAP2K1 mutation status were successfully determined with NGS. BRAFV600E was detected in 26 patients (38.8%), BRAFV600D was detected in 1 patient (1.5%), BRAFT599I in 1 patient (1.5%) and BRAFdeletion mutation in 17 patients (25.4%), including 15 BRAF N486_P490 and 2 BRAF N486_P491delinsS. MAP2K1 mutation was detected in 13 patients (19.4%). BRAF status was related to disease features and extent of disease. BRAF deletion was found in 38.5% of patients with MS LCH, 7.1% of patients with SS LCH (P= 0.004). BRAF deletion was apparent in 69.2% of patients with liver involvement (P <0.001). While bone involvement was associated with BRAFV600E mutation (46.2% vs 13.2%, P = 0.033). The initial treatment of the whole cohort is illustrated in the flow diagram of Figure 1. The estimated 4-year OS and EFS of patients with SS-s LCH were 97.2% and 57.0%, respectively. Totally 201 MS or SS-m patients received first-line treatment at our hospital. After a median 43-month follow-up (range 1-214 months), 92 patients had reactivation. The median EFS was 38.5 months (95% CI, 20.9-56.1 months). To evaluate the prognostic factors of EFS using multivariate Cox regression model, the involvement of liver (HR 0.545, 95% CI 0.335-0.885) or spleen (HR 0.416, 95% CI 0.205-0.844) at baseline were predictive of poor EFS, while receiving cytarabine-based therapy as a first-line treatment (HR 2.195, 95% CI 1.441-3.344) and age older than 30 years at diagnosis (HR 1.660, 95% CI 1.087-2.533) predicted favorable EFS. BRAF or MAP2K1 mutation status did not significantly affect EFS. Seventeen patients died during follow-up. The estimated 4-year OS was 94.4% of patients with MS or SS-m. Conclusion: We first found more than 25% of adult LCH patients carried BRAFdeletion (BRAF N486_P490 or BRAF N486_P491delinsS), which was related with MS and liver involvement. Also, we demonstrated that liver and spleen involvement indicates a worse prognosis in adult LCH, age older than 30 years at diagnosis predicted favorable EFS and a cytarabine-based regimen should be considered as a first-line treatment for adult MS or SS-m LCH patients. Disclosures No relevant conflicts of interest to declare.

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Góralski, Wojciech. "Eucharystia w statutach synodu płockiego z 1733 r." Prawo Kanoniczne 30, nr 3-4 (10.12.1987): 48–62. http://dx.doi.org/10.21697/pk.1987.30.3-4.03.

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II sinodo diocesano di Andraa Stanislao Załuski, vescovo di Płock, celebrato nei giorni i 4-5 agosto 1733 a Pułtusk, fu convocato per trattare le cose che si riferivano alle necessità particolari del clero e del popolo della diocesi di Płock. La redazione degli statuti sinodali contiene 47 articuli riguardanti tra l’altro la disciplina dei sacramenti. In questa sfera domina la problematica della Eucarestia contenuta nei quattro articoli: De Echaristia (14), De Sacrificio Missae (15), De conservatione Sanctissimi Sacramenti, processionibus cum eodum atque eius expositionibus (16), De oneribus Missarum reductioneque eorum (17). L’autore presenta le rispettive disposizioni di suddetti articoli riguardanti la s. messa, la s. comunione, la custodia e il culto della ss. Eucarestia. Il complesso di quel frammento degli statuti sinodali dimostra che il clero della diocesi di Płock ha ricevuto un aiuto molto importante nella strada sempre aperta verso la realizzazione della riforma tridentina.

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Fraccari, Raquel L., Marco Carminati, Giacomo Piantanida, Tina Leontidou, Giorgio Ferrari i Tim Albrecht. "High-bandwidth detection of short DNA in nanopipettes". Faraday Discussions 193 (2016): 459–70. http://dx.doi.org/10.1039/c6fd00109b.

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Glass or quartz nanopipettes have found increasing use as tools for studying the biophysical properties of DNA and proteins, and as sensor devices. The ease of fabrication, favourable wetting properties and low capacitance are some of the inherent advantages, for example compared to more conventional, silicon-based nanopore chips. Recently, we have demonstrated high-bandwidth detection of double-stranded (ds) DNA with microsecond time resolution in nanopipettes, using custom-designed electronics. The electronics design has now been refined to include more sophisticated control features, such as integrated bias reversal and other features. Here, we exploit these capabilities and probe the translocation of short dsDNA in the 100 bp range, in different electrolytes. Single-stranded (ss) DNA of similar length are in use as capture probes, so label-free detection of their ds counterparts could therefore be of relevance in disease diagnostics.

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Klokkevold, Katherine N., Weston Keeven, Dong Hun Lee, Michael Clevenger, Mingyuan Liu, Kwangsoo No, Han Wook Song i Sunghwan Lee. "Low-temperature metal/Zerodur heterogeneous bonding through gas-phase processed adhesion promoting interfacial layers". AIP Advances 12, nr 10 (1.10.2022): 105224. http://dx.doi.org/10.1063/6.0002114.

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The bonding of ceramic to metal has been challenging due to the dissimilar nature of the materials, particularly different surface properties and the coefficients of thermal expansion (CTE). To address the issues, gas phase-processed thin metal films were inserted at the metal/ceramic interface to modify the ceramic surface and, therefore, promote heterogeneous bonding. In addition, an alloy bonder that is mechanically and chemically activated at as low as 220 °C with reactive metal elements was utilized to bond the metal and ceramic. Stainless steel (SS)/Zerodur is selected as the metal/ceramic bonding system where Zerodur is chosen due to the known low CTE. The low-temperature process and the low CTE of Zerodur are critical to minimizing the undesirable stress evolution at the bonded interface. Sputtered Ti, Sn, and Cu (300 nm) were deposited on the Zerodur surface, and then dually activated molten alloy bonders were spread on both surfaces of the coated Zerodur and SS at 220 °C in air. The shear stress of the bonding was tested with a custom-designed fixture in a universal testing machine and was recorded through a strain indicator. The mechanical strength and the bonded surface property were compared as a function of interfacial metal thin film and analyzed through thermodynamic interfacial stability/instability calculations. A maximum shear strength of bonding of 4.36 MPa was obtained with Cu interfacial layers, while that of Sn was 3.53 MPa and that of Ti was 3.42 MPa. These bonding strengths are significantly higher than those (∼0.04 MPa) of contacts without interfacial reactive thin metals.

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Kaluzny, Bartlomiej J., Joanna Stachura, Patryk Mlyniuk, Alfonso Jimenez-Villar, Magdalena Wietlicka-Piszcz i Ireneusz Grulkowski. "Change in the geometry of positive- and negative-powered soft contact lenses during wear". PLOS ONE 15, nr 11 (9.11.2020): e0242095. http://dx.doi.org/10.1371/journal.pone.0242095.

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Contact lens wear causes mutual interactions between the ocular surface and the lens, which may affect comfort as well as vision. The aim of this study was to examine deformations in modern positive- and negative-powered silicone hydrogel soft contact lenses (SiH SCLs) after 7 days of continuous wear. This pre-post interventional study included 64 eyes: 42 eyes with myopia of -3.00 D and 22 eyes with hyperopia of +3.00 D. All patients underwent general ophthalmic examination, corneal topography/tomography, total corneal and epithelial thickness mapping, and specular microscopy before and after the wearing period. SiH SCLs made of senofilcon A were worn continuously for 7 days on all eligible eyes. The geometry of the new and used lenses was measured 3 to 6 minutes after removal in two perpendicular planes using a custom-made swept source optical coherence tomography (SS-OCT) system for in vitro measurements. The anterior and posterior radii of curvature decreased in -3.00 D lenses in two perpendicular planes. This effect correlated significantly with average keratometry of the cornea. Sagittal lens height was lower in +3.00 D lens after wear, which correlated moderately with the corneal sagittal height. A significant decrease in central corneal epithelial thickness was observed after wearing +3.0 D lenses. In conclusion, SiH SCLs made of senofilcon A undergo minor deformations after 7-day continuous wear. Geometry modifications are different for -3.00 D and +3.00 D lenses, and they imitate the shape of the anterior eye surface. These geometric changes are accompanied by a decrease in the central thickness of corneal epithelium after +3.00 D lens wear.

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Hillen, Maarten R., Eleni Chouri, Maojie Wang, Sofie L. M. Blokland, Sarita A. Y. Hartgring, Arno N. Concepcion, Aike A. Kruize i in. "Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sjögren’s syndrome is associated with processes at the centre of their function". Rheumatology 58, nr 12 (25.05.2019): 2305–14. http://dx.doi.org/10.1093/rheumatology/kez195.

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Abstract Objective A considerable body of evidence supports a role for type-I IFN in the pathogenesis of primary SS (pSS). As plasmacytoid dendritic cells (pDCs) are a major source of type-I IFN, we investigated their molecular regulation by measuring expression of a large set of miRNAs. Methods pDCs were isolated from peripheral blood of pSS patients (n = 30) and healthy controls (n = 16) divided into two independent cohorts (discovery and replication). Screening of 758 miRNAs was assessed by an OpenArray quantitative PCR-based technique; replication of a set of identified miRNAs was performed by custom array. Functional annotation of miRNA targets was performed using pathway enrichment. Novel targets of miR-29a and miR-29c were identified using a proteomic approach (stable isotope labelling with amino acids in cell culture). Results In the discovery cohort, 20 miRNAs were differentially expressed in pSS pDCs compared with healthy control pDCs. Of these, differential expression of 10 miRNAs was confirmed in the replication cohort. The dysregulated miRNAs were involved in phosphoinositide 3-kinase-Ak strain transforming and mammalian target of rapamycin signalling, as well as regulation of cell death. In addition, a set of novel protein targets of miR-29a and miR-29c were identified, including five targets that were regulated by both miRs. Conclusion The dysregulated miRNome in pDCs of patients with pSS is associated with aberrant regulation of processes at the centre of pDC function, including type-I IFN production and cell death. As miR-29a and miR-29c are pro-apoptotic factors and several of the novel targets identified here are regulators of apoptosis, their downregulation in patients with pSS is associated with enhanced pDC survival.

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Tay, David. "(428) Seed Threshing and Cleaningin Flowers". HortScience 40, nr 4 (lipiec 2005): 1023C—1023. http://dx.doi.org/10.21273/hortsci.40.4.1023c.

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Flower seed threshing and cleaning are challenging because many flowers have tiny seed, e.g., the 1000-seed weight of Begonia is 0.01 g, and others have odd-shaped seed, e.g., Tagetes has pappus-bearing seed and Fibigia has winged seed. There is a lack of information on the threshing and cleaning of flower seeds. At the Ornamental Plant Germplasm Center, a small-plot grain belt thresher was modified by disengaging its winnower and a special chute installed to collect the threshed seed and chaff together for cleaning. A custom-made threshing board is used for small samples. The seed with chaff is passed through screen with mesh size that allows all the seed to pass through so that the big pieces of chaff are retained and separated, i.e., scalping. Accurate selection of the next scalping screen (SS) is critical so that the mesh size is just right for at least 95% of the seed to pass through to remove all the chaff larger than the seed. The seed is then sieved on a grading screen (GS) of mesh size that retains at least 95% of the seed to remove all the chaff smaller than the seed. A seed blower is used to further separate the remaining chaff and empty seed based on weight and surface area by adjusting the blowing velocity (BV). A vibratory separator (VS) is used for species with round seed, e.g., Antirrhinum. An X-ray machine is used to monitor the cleaning process. The SC, GS, BV, and VT are given for Agastache, Anisodontea, Antirrhinum, Aquilegia, Aster, Astilboides, Begonia, Belamcanda, Bergenia, Cleome, Coreopsis, Dianthus, Eupatorium, Gaillardia, Geranium, Gypsophila, Iris, Lilium, Lysimachia, Myosotis, Nothoscordom, Oenothera, Passiflora, Penstemon, Petunia, Platycodon, Ranunculus, Rudbeckia, Silene, Stokesia, Synnotia, Tagetes, Talinum, Thalictrum, Verbena, Veronica, and Zinnia.

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G.*, Bhusnure O., Gholve V. S., Sugave B. K., Dongre R. C., Gore S. A. i Giram P. S. "3D Printing & Pharmaceutical Manufacturing: Opportunities and Challenges". International Journal of Bioassays 5, nr 01 (1.01.2016): 4723. http://dx.doi.org/10.21746/ijbio.2016.01.006.

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Many researchers have attempted to use computer-aided design (C.A.D) and computer-aided manufacturing (CAM) to realize a scaffold that provides a three-dimensional (3D) environment for regeneration of tissues and organs. As a result, several 3D printing technologies, including stereolithography, deposition modeling, inkjet-based printing and selective laser sintering have been developed. Because these 3D printing technologies use computers for design and fabrication, and they can fabricate 3D scaffolds as designed; as a consequence, they can be standardized. Growth of target tissues and organs requires the presence of appropriate growth factors, so fabrication of 3Dscaffold systems that release these biomolecules has been explored. A drug delivery system (D.D.S) that administrates a pharmaceutical compound to achieve a therapeutic effect in cells, animals and humans is a key technology that delivers biomolecules without side effects caused by excessive doses. 3D printing technologies and D. D. Ss have been assembled successfully, so new possibilities for improved tissue regeneration have been suggested. If the interaction between cells and scaffold system with biomolecules can be understood and controlled, and if an optimal 3D tissue regenerating environment is realized, 3D printing technologies will become an important aspect of tissue engineering research in the near future. 3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fuelled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. Until recently, tablet designs had been restricted to the relatively small number of shapes that are easily achievable using traditional manufacturing methods. As 3D printing capabilities develop further, safety and regulatory concerns are addressed and the cost of the technology falls, contract manufacturers and pharmaceutical companies that experiment with these 3D printing innovations are likely to gain a competitive edge. This review compose the basics, types & techniques used, advantages and disadvantages of 3D printing

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Stallings, Alicia M., Navneet S. Majhail, Amy S. Nowacki, Grace I. Onimoe, Rabi Hanna, Jillian Wen, Charles T. Quinn, Lewis L. Hsu i Connie M. Piccone. "Parent and Guardian Knowledge of Hematopoietic Cell Transplantation As a Treatment Option for Sickle Cell Disease". Blood 128, nr 22 (2.12.2016): 1307. http://dx.doi.org/10.1182/blood.v128.22.1307.1307.

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Abstract Introduction: Beginning early in childhood, patients with sickle cell disease (SCD) are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, hematopoietic cell transplantation (HCT), the only curative therapy for SCD, remains underutilized. Between 2008 and 2012, an average of 76 HCTs per year were performed on patients with SCD in the United States (US), a remarkably low rate considering that nearly 100,000 people in the US are living with this disease and approximately 1,000 infants are born with SCD in the US each year. Multiple factors may contribute to the low rates of HCT in this population. However, there is a paucity of data concerning the level of awareness of HCT among parents and guardians of children with SCD, an important factor to consider in the assessment of HCT utilization rates. Objectives: To identify the proportion of parents and guardians of children with SCD who are aware of HCT as a treatment option, and to evaluate the relationship between patient demographics and parental/guardian awareness of this treatment option. Methods: A 25-item paper-based survey was developed to assess parent/guardian awareness of HCT, based upon feedback from leaders in SCD community health organizations and pediatric hematologists. The survey was administered to parents/guardians of pediatric patients with SCD during routine outpatient appointments with their child's hematologist and at SCD community events sponsored by participating clinical sites. The survey was anonymous, and a $5.00 gift card was provided to all participants who completed the survey. Participants were recruited from four clinical centers across three cities in the Midwestern United States. All parents/legal guardians of children (<18 years of age) with SCD, who have not undergone HCT, were eligible to participate. Multivariable logistic regressions were performed to assess the relationship between the following variables and parent/guardian awareness of HCT as a treatment option for SCD: accrual site, patient age, number of full siblings, parent/guardian education level, parent/guardian relationship to patient, duration of custody, and SCD genotype. Results: 229 respondents (95% biological parent, 1% adoptive parent, 4% legal guardian) have participated in the study to date. 95% of all eligible parents/guardians agreed to participate. 82% of study respondents indicated that they have heard of HCT as a treatment option for SCD (N=187). 53% indicated that their child's physician has talked to them about HCT at some point in the past (N=120). On average, patients were 2.84 years old when the parent/guardian first heard about HCT (N=178, 95% CI: 2.31-3.37); patients were 3.08 years old on average when the child's physician first mentioned HCT (N=113, 95% CI: 2.42-3.75). 76% of respondents indicated that they are aware that HCT can potentially cure SCD (N=172). Higher parent/guardian education level and SS genotype were associated with having heard about HCT as a treatment option. SS genotype was associated with having been informed about HCT by their child's physician. Having been informed about HCT by their child's physician was associated with parent/guardian awareness that HCT is a potentially curative treatment. Conclusions: The majority of parents/guardians of children with SCD enrolled in this study have heard of HCT and are aware that HCT is a potentially curative treatment. In this population, non-physician sources of information and parent/guardian education level play an important role in awareness of this treatment modality. Physician-family discussion about HCT plays an important role specifically in parent/guardian awareness of the curative potential of this treatment. These data underscore the importance of physicians discussing HCT with families, particularly those who have limited resources to research treatment options on their own. Disclosures Quinn: Amgen: Research Funding; Eli Lilly: Research Funding; Silver Lake Research Corporation: Consultancy. Hsu:Centers for Medicare and Medicaid Innovation: Research Funding; Mast Therapeutics: Research Funding; Pfizer: Consultancy, Research Funding; Purdue Pharma: Research Funding; Sancilio: Research Funding; Gerson Lehman Group: Consultancy; Eli Lilly: Research Funding; EMMI Solutions: Consultancy; Astra Zeneca: Consultancy, Research Funding; Hilton Publishing: Consultancy, Research Funding. Piccone:Novartis: Other: Speaker.

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Alizadeh, Ash A., Andrew J. Gentles, Sylvia K. Plevritis i Ronald Levy. "Gene Expression Signature of Host Immune Response Is Predictive of Follicular Lymphoma Patient Survival in Independent Cohorts, and Correlates with Transformation to Diffuse Large B-Cell Lymphoma." Blood 114, nr 22 (20.11.2009): 2951. http://dx.doi.org/10.1182/blood.v114.22.2951.2951.

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Abstract Abstract 2951 Poster Board II-927 Background: Expression signatures of infiltrating immune cells [1] have been shown to predict survival in follicular lymphoma (FL), but have not been cross-validated in independent patient cohorts [2,3]. These signatures may relate biologically to the frequency of infiltrating including T-cells and macrophages, or to specific transcription programs within tumor cells and/or the tumor microenvironment. We sought to evaluate the validity of this model in an independent cohort of patients with FL, assessing its relationship to outcomes including histological transformation and death. Methods: The immune response (IR) predictor score proposed by Dave et al. [1] was applied to gene expression data from an independent cohort of 88 FL patients [4] with known survival outcomes and history of transformation to diffuse large B-cell lymphoma (DLBCL). Genes (n=66) corresponding to IR1 and IR2 signatures were mapped from Affymetrix microarrays [1] to a custom cDNA array [4] via Entrez Gene ID, and the composite IR score was calculated per the scheme proposed by Dave et al. Results: The IR score was predictive of patient outcome in the 88 patient test set as a continuous variable (p=0.001, HR=2.01, 95% CI 0.50-1.30). Partitioning of patients into high and low risk groups based on the median IR score across the cohort robustly separated survival curves (Figure A). The IR score was significantly higher in FL patients known to undergo transformation to DLBCL (Figure B: mean IR score of -0.6 in non-transforming FL vs. -0.2 in transforming FL; p∼10-11, t-test). Conclusions: The IR score of Dave et al. was highly significant as a predictor of survival in the independent patient cohort [4]. Moreover, the score was significantly associated with propensity of FL to transform to DLBCL. To our knowledge, immune cell infiltration has not previously been implicated in transformation. 1. Dave SS et al. (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 351(21): 2159-2169. 2. Tibshirani R (2005) Immune signatures in follicular lymphoma. N Engl J Med 352: 1496-1497. 3. Chu G Hong WJ, Warnke R, Chu G (2005). Immune Signatures in Follicular Lymphoma (Corres). N Engl J Med. 352: 1496-1497. 4. Glas AM et al. (2005) Gene expression profiling in follicular lymphoma to assess clinical aggressiveness and to guide the choice of treatment. Blood 105(1): 301-307. Disclosures: No relevant conflicts of interest to declare.

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Adekile, Adekunle, Nagihan Akbulut Jeradi, Maria Fernandez i Rasha Al-Khaldi. "The Diagnosis of HbS Genotypes and Identification of β-Thalassemia Mutations in Patients with Hbsβ-Thalassemia Using Next Generation Sequencing". Blood 136, Supplement 1 (5.11.2020): 38. http://dx.doi.org/10.1182/blood-2020-139869.

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The conventional diagnosis of sickle cell disease (SCD) depends on RBC morphology, Hb electrophoresis and/or high-performance liquid chromatography (HPLC). However, these methods are fraught with ambiguities especially in areas where HbSβ-thalassemia is common. The distinguishing laboratory feature between patients with HbSS and HbSb-thalassemia is the level of HbA2. Unfortunately, when HbA2 is estimated with HPLC in patients with Sβthalassemia, it tends to be spuriously high because it co-migrates with glycated HbS. HbSβ-thalassemia accounts for 30 - 40% of the SCD patients being followed in Kuwait. Patients with a presumptive diagnosis of HbSS and/or Sβ-thalassemia, by HPLC were referred to the Hemoglobin Research Laboratory of Department of Pediatrics, Kuwait University for confirmatory molecular diagnosis. The DNA samples collected from 1994 to 2018 were recently subjected to NGS. DNA was isolated from peripheral leukocytes using the phenol-chloroform method. The Illumina Ampliseq custom DNA panel was used to genotype the DNA samples. For theHBBlocus, all β-globin mutations and variants were confirmed by arrayed primer extension (APEX) or Sanger sequencing methods. In addition, genotyping of modifier SNPs inBCL11Aon chromosome 2 and theHBS1L-MYBintergenic region on chromosome 6 was carried out to identify their influence on HbF expression among our patients. In all, 126 SNPs were genotyped. We hereby, report the false positive and false negative rates for the diagnosis of Sb-thalassemia with HPLC compared to NGS. We also report the spectrum of β-thal mutations among our patients with Sβ-thalassemia. The DNA samples were from 232 patients aged from 1 to 59 with a mean of 12.7 ± 11.2 years. Analysis of the initial HPLC diagnosis showed that 27.7% were reported to have Sβ-thalassemia, while after NGS assessment, 29.4% were found to truly fit the diagnosis. Three individuals who were diagnosed as HbSS turned out to be HbAS and 1 each turned out to be HbAA and β-thalassemia trait respectively. Twelve patients that were originally thought to be Sβ-thalassemia turned out to be HbSS, i.e. a false positive rate of 5%, while 30 who were thought to be SS, turned out to be Sβ-thalassemia, i.e. a false negative rate of 13%. A total of 12 mutations were identified in 61 Sβ-thalassemia patients. Of these, the most common were the β0 IVS-1 del 25 and the IVS-II-1 (G/A) in 9 (14.8%) each. The most common β+ mutation was the IVS-I-110 (G/A) in 8 (13.1%), followed by the IVS-I-5 (G/C) in 7 (11.5%). While the Sβ0-thalassemia patients had no HbA on HPLC, the Sβ+ were associated with varying concentrations of HbA, ranging from 0 for those carrying the IVS-I-5 (G/C) mutation to a mean of 15.5 +/- 6.2% in the patients with IVS-I-110 (G/A) and 25.1% in the Sβ++patient with IVS-I-6 (C/T). Indeed, HPLC is far from deal in detecting HbSβ-thalassemia with significant rates of false positivity and negativity. NGS is very versatile; it can interrogate thousands of genes simultaneously, making it ideal for use in SCD. The HbS genotype, β-thalassemia mutation, haplotype and different modifier polymorphisms can be determined in one run. It is therefore very useful for personalized diagnosis that can document prognostic factors, making for purposeful counseling and follow-up from an early age. Disclosures No relevant conflicts of interest to declare.

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Kutlar, Abdullah, Leigh G. Wells, Hongyan Xu, Latanya Bowman, Pritam Bora, Arati Rani Chand, Betsy Clair i in. "Genetic Association Studies of Pain Phenotypes in Adult SCD Patients". Blood 124, nr 21 (6.12.2014): 2708. http://dx.doi.org/10.1182/blood.v124.21.2708.2708.

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Abstract Vasoocclusive episodes (VOEs) are the hallmark of sickle cell disease (SCD) responsible for > 90% of health care utilization. Several studies have elucidated the spectrum of pain syndromes in SCD and have led to the recognition of chronic, neuropathic, and centralized pain in these patients. We previously reported that adult SCD patients exhibited significant hyperalgesia in response to pressure pain algometer testing compared to age, race, and sex matched controls. While demographic and anthropometric factors were associated with self-reported pain, distress, and pressure pain threshold, genetic associations were not tested. Thus, we studied genetic polymorphisms in 167 adult patients with SCD (SS and Sb0-thal). Data were collected on number of hospitalizations, ED visits, and opioid use (morphine equivalents) in the past 12 months. Daily pain, subjective distress, and interference with daily activities were measured using daily diaries (as in the PiSCES study) over a period of 6 months. Subjects underwent mechanical pain testing with a pressure algometer at 3 anatomic sites (masseter, ulna, and trapezius) during steady state. Blood samples were obtained for ascertainment of SCD genotype and DNA extraction. Genotyping was performed at the University of Florida Genomics Facility using the Algynomics (Chapel Hill, NC) Pain Research Panel, a custom made chip utilizing the Affymetrix MegAllele technology. The panel assesses 3,295 SNPs representing 358 genes known to be involved in systems relevant to pain perception, nociceptive transmission, inflammation, mood, and affect. Individuals with >10% missing data were excluded from analysis. Hardy-Weinberg Equilibrium was checked for the genotypes at each SNP with a chi-squared test. A total of 328 rare SNPs with minor allele frequencies (<1%) were dropped. The final pain phenotypes included experimental pain, distress, interference with daily activities, opioid usage, and hospitalizations / ED visits. Linear regression was fitted to each SNP, regressing each phenotype onto genotype under an additive model, with age, gender, and BMI as covariates. The analysis was performed using Plink. False discovery rate was controlled using the Benjamini & Hochberg method. Six SNPs in 5 genes (ESR2, KCNJ11, DBH, ATP1A1, CACNA2D2) were significantly associated with pressure pain threshold. ESR2 polymorphisms have been reported to be associated with temporomandibular, synovial, and neurogenic pain. KCNJ11 has been reported to play an important role in opioid sensitivity/analgesia. DBH polymorphisms have been related to analgesia, migraines, and catecholamine and serotonin metabolism. ATP1A1 was reported in association with headaches and paresthesias. CACNA2D2 has been correlated with increased sensitivity to opioids. In terms of opioid usage, 3 SNPs (CAMK2B, PRKD1, CACNA2D4) had significant associations and have been reported to be related to stress, depression, neuronal connectivity, pain modulation, neurogenic inflammation, and pain transmission. ED visits were significantly associated with 3 SNPS (TRIM31, PLAUR, PRKG1), which have been reported to be associated with fibromyalgia, nociceptive processing, and inflammation. Two SNPs (PRL and ADRA1A) were significantly associated with hospitalizations that have previously been related to nociception and hyperalgesia as well as inflammation and allodynia. To our knowledge, this is the first detailed study of genetic associations with different pain related phenotypes in subjects with SCD. Our results show that SNPs in genes relevant to pain processing, nociception, hyperalgesia, opioid sensitivity, inflammation, and stress are significantly associated with different pain phenotypes and therefore appear functionally relevant in adults with SCD. These findings will hopefully serve as a discovery cohort, which should be validated in an independent group of SCD patients. A better understanding of pathways and networks relevant to SCD pain may ultimately lead to new therapeutic interventions. Disclosures Kutlar: NIH/NIMHD: Research Funding. Wells:NIH/NIMHD: Research Funding. Xu:NIH/NIMHD: Research Funding. Bowman:NIH/NIMHD: Research Funding. Bora:NIH/NIMHD: Research Funding. Clair:NIH/NIMHD: Research Funding. Meiler:NIH/NIMHD: Research Funding. Wang:NIH/NIMHD: Research Funding. Fillingim:NIH/NIMHD: Research Funding; Algynomics: Equity Ownership.

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Mannino, Robert, David R. Myers, Byungwook Ahn, Hope Gole, Yichen Wang, Angela Lin, Robert Guldberg, Don Giddens, Lucas Timmins i Wilbur A. Lam. "Vascular Geometry and Flow Profile Mediate Pathological Cell-Cell Interactions in Sickle Cell Disease As Measured with "Do-It-Yourself" "Endothelial-Ized" Microfluidics". Blood 124, nr 21 (6.12.2014): 454. http://dx.doi.org/10.1182/blood.v124.21.454.454.

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Abstract Background and Significance: Cell-cell interactions between blood cells and endothelial cells play an important role in sickle cell disease (SCD) pathophysiology. While in vivo transgenic animal models and in vitro systems have both contributed to our understanding of these pathologic cell-cell interactions in SCD, isolating the causes and effects of cellular interactions is exceedingly difficult in the former and recapitulating the complex vascular geometries found in vivo is not readily available with current systems in the latter. The vascular system comprises diverse geometries that range from normal (e.g. curves and bifurcations) to pathologic (e.g. aneurysms and stenoses) and as blood flows from one vascular geometry to another, the local shear stress profile acutely changes. Interestingly, changes in shear stress are known to alter endothelial pro-inflammatory signaling pathways and expression of cell adhesion molecules, especially vascular cell adhesion molecule-1(VCAM-1) (Tzima, Nature, 2005), which is implicated in SCD vasculopathy. Here we present a rapid and inexpensive method using only off-the-shelf materials to create “do-it-yourself” (DIY) microfluidic devices that incorporate endothelial cells and clinically relevant vascular geometries; this system effectively and bridges current in vitro and in vivo models to study SCD. Using this technique, we developed a vascularized bifurcation, and observed that shear stress changes can be extremely localized, affecting only several 10s of cells, and are associated with changes in VCAM1 expression. We used this in vitro vascularized bifurcation to test the hypothesis that SS RBC-endothelial cell adhesion occurs primarily at bifurcations, which are difficult to visualize in vivo (Nagel, Arterioscler Thromb Vasc Biol, 1999). We demonstrate that SCD RBCs do primarily aggregate at bifurcations, specifically in locations where the shear stress has decreased and VCAM-1 is upregulated. Methods: In order to bridge in vitro data with the complex vascular geometric environments found in vivo, we developed a “DIY” endothelialized microfluidic model (Figure 1A). A strand of 500um diameter polymethylmethacrylate (PMMA) optical fiber is laid flat on top of a layer of polydimethylsiloxane (PDMS) and covered with a second, thin layer of PDMS. After curing, the optical fiber is pulled out, exposing a hollow, circular, channel that can be used as a microchannel to seed endothelial cells. A wide variety of endothelial cells can be successfully seeded in these devices, such as human umbilical vein endothelial cells, human aortic endothelial cells, and human microvascular endothelial cells. Slight alterations to this fabrication method result in the creation of multiple vascular geometries, such as curved or bifurcated channels with or without aneurysms or stenoses. Results: Curved channels & bifurcations (Figure 1B-C) are seeded with endothelial cells (Figure 1E-F). Computational fluidic dynamics calculations show that the shear varies by 2.5 fold within the bifurcation. As shear affects endothelial expression, we tested if the extremely localized shear changes created in this system were sufficient to alter local endothelial expression of VCAM-1 Indeed, in our system, VCAM1 expression significantly correlated with shear variation (Figure1G), and was highest near the bifurcation point. Noting this localized variation in adhesion molecule expression, we tested whether the bifurcations are implicated in SCD RBC adhesion to the endothelium. With our vascularized bifurcation model and custom image analysis software that quantifies RBC aggregation, we observed that SCD RBC adhesion predominantly occurred at the point of bifurcation where the shear is lowest and VCAM1 expression is greatest, and minimal endothelial adhesion occurred with healthy control RBCs (Figure 2). This phenomenon persisted with tumor necrosis factor-stimulation of the endothelium. Conclusion: This DIY system represents an easily accessible technique that allows any researcher to bridge the gap between in vitro and in vivo models of pathological cell-cell interactions in SCD. We demonstrate that recapitulating the complex vascular geometries in vivo is vital to understanding blood cell-endothelial interactions and this system will not only be useful for studying SCD, but a myriad of hematologic and vascular diseases as well. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Carden, Marcus A., Meredith Ellen Fay, Yumiko Sakurai, Robert G. Mannino, Jordan Ciciliano, Reginald Tran i Wilbur A. Lam. "Commonly Used Clinical Intravenous Fluid Formulations Differentially Affect Sickle Red Blood Cell Stiffness and Transit Time". Blood 126, nr 23 (3.12.2015): 2164. http://dx.doi.org/10.1182/blood.v126.23.2164.2164.

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Abstract Background: Disruption of red blood cell (RBC) volume regulation and water homeostasis is a major component of sickle cell pathophysiology. As such, hydration is a mainstay of prevention and treatment of vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). However, evidence for guiding clinicians' choice for intravenous (IV) fluid hydration in the acute setting is lacking (Okomo, Coch Data Syst Rev, 2012). Pediatric hematologists typically discourage rapid infusion of hypotonic fluid given the risk of hyponatremia, although such fluids as 5% dextrose with 34meq/L or 77meq/L sodium are often used after stabilizing various acute clinical situations relevant to SCD. Although altered sodium concentration and osmolarity have been shown to affect erythrocyte swelling and rheology, dextrose-containing fluids used clinically such as D5 ¼ and D5 ½ normal saline (NS), have not been studied (Reinhart et al., Mic Res, 2015; Hijiya et al., J Lab Clin Med, 1991). To those ends, we sought to investigate the effect of different clinically relevant IV fluid formulations on normal and sickle RBC stiffness and deformability. Methods: Fresh blood was obtained from healthy volunteers and patients with sickle cell anemia (SS) on hydroxyurea and not transfused for at least 100 days. Sterile, clinical grade fluids stored at room temperature were used for the experiments (Baxter, Figure 1A). Our laboratory has previously published a description of a microfluidic device comprised of multiple parallel microchannels 5μm wide recapitulating the in vivo geometry of capillaries (Rosenbluth et al., Lab Chip, 2008). This microvasculature-on-a-chip enables measurements of single-RBC transit times, which correlate with cell stiffness (Figure 1B,C). For the transit time experiments, a master silicon wafer was used to mold the microfluidic channels out of polydimethylsiloxane (PDMS) silicone. Centrifuged RBCs were washed with phosphate-buffered saline (PBS) and then diluted to 0.5% hematocrit (HCT) in the various fluids prior to flow. Cell suspensions were perfused into a microfluidic device pre-coated with 2% bovine serum albumin (BSA) at an average linear flow rate of 0.50 mm s-1 in the smallest channels with a syringe pump (Harvard Apparatus) and then imaged at 20x at 20 frames per second. Images were recorded for future analysis. For the experiments assessing RBC shape, washed RBCs were diluted with PBS to 0.5% HCT and imaged at 40x in plastic wells at time 0. PBS was removed and 100 μL of each clinical fluid formulation was added to the wells and images were then obtained over time. RBC circularity was calculated using custom-written scripts in Matlab (Figure 1D). Results: RBC transit times in both healthy and sickle blood were affected by osmolarity and the various solute concentrations (Figures 2A,B). Transit times of sickle RBCs in all IV fluid formulations were significantly higher, over 10 times, than that of RBCs from healthy donors. Transit times for both healthy and sickle donors were least in the D5 ¼ NS solution. Of note, sickle RBC transit time was greatest in the NS solution. Sickle RBC circularity also changed with solute concentration and osmolarity with statistical significance (Figure 2C). Cells with the highest change in circularity from baseline were also those exposed to the D5 ¼ NS solution. Conclusion: Our results suggest the stiffness of sickle RBCs is affected by different formulations of clinical IV fluids. Increased transit time of sickle RBCs in NS through our device may in part be explained by the decreased circularity, indicating that RBCs adopt more irregular shapes in this fluid. This, in turn, could lead to increased propensity of microchannel obstruction. Although the exact mechanisms are unclear, this begs the question of whether NS is an appropriate choice for initial fluid resuscitation for VOC and other SCD-related complications as it could exacerbate the already high stiffness and shape irregularity of sickle RBCs, further increasing microvascular occlusion. As these in vitro results have significant clinical implications, ongoing experiments involve investigating how these fluid-dependent effects may alter sickle RBC adhesion in 'endothelialized' microfluidic devices, how different oxygen tensions affect these fluid-mediated effects, potential differences on and off of hydroxyurea, and the underlying mechanisms of this IV fluid formulation-dependent effect. Disclosures No relevant conflicts of interest to declare.

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Kolb, E. Anders, Erin Coyne, Erin Crowgey, Villanueva Raymond, Jean Wadman, Sidnie Jacobs-Allen i Robin E. Miller. "Improving Care of Patients with Sickle Cell Disease through Discrete Clinical Data Extraction and Automated Analysis of the Electronic Healthcare Records". Blood 128, nr 22 (2.12.2016): 2331. http://dx.doi.org/10.1182/blood.v128.22.2331.2331.

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Abstract Introduction Analyzing population and individual trends within a disease cohort is essential to develop efficient strategies for improving patient care. A current limitation stems from the lack of searchable, structured and well defined (granular) data elements within electronic health records (EHR). Sickle cell disease (SCD) is characterized by varying genotypes and disease severity. Without disease-specific customization in the EHR, clinicians are limited to basic types of data driven by ICD coding. Most institutions are discovering that ICD coding-base data queries are not always accurate. Improving the availability of granular data elements relevant to SCD allows us to utilize complex and meaningful data queries to impact patient care. Methods All current SCD patients at a single institution were identified (n=253, median age 8 years, 52.2% female). Disease status was validated by electrophoresis and/or genotype. A severity grading scale was created for the following SCD adverse events (AEs): acute chest syndrome (ACS), vaso occlusive crisis (VOC), summarized in Table 1. A 5 year retrospective chart review of inpatient encounters was performed for ACS and VOC using our patient list. AEs were graded on a numeric scale from 1 to 5. For this review, only higher grade events requiring admission are reported. Grade (G) 3 VOC denotes IV opioid use < 5 days, and G4 is > 5 days. G3 ACS denotes moderate to severe respiratory distress requiring non-invasive ventilation, and G4 is life-threatening distress with urgent intervention. All data abstractions and severity grades were confirmed by a provider with more than 5 years experience in SCD clinical care. A custom flowsheet navigator section (Epic 2014) was used to capture AEs. To address health maintenance needs, a SCD Well Visit SmartForm (WVS) was implemented in Epic. All relevant data elements were captured in an Epic SmartForm utilizing a data dictionary with common terminology. The WVS contains all aspects of routine SCD health surveillance including baseline values, as well as 20 SCD co-morbidities that can be assigned to a patient and expanded upon. The WVS was completed for all patients with HgbSS and Sβeta0 Thalassemia via chart review by 2 SCD APNs. EHR-based queries using Epic 2014 Reporting Workbench/Crystal Reports 2008 were generated from the validated patient list rather than ICD 9 or ICD 10 disease classification. Results For ACS and VOC, we completed abstraction of 1374 independent inpatient encounters for 253 total patients with SCD from 2010-15. There were 598 G3 and G4 VOC encounters among 137 individual patients. There were 62 G3 and G4 ACS encounters among 41 individual patients. Results are summarized in Table 1. This approach enabled automated tracking of AEs in a cohort of patients with recurrent severe VOC (n=34) and recurrent severe ACS (n=13). The duration and severity of cumulative as well as inter-current adverse events are smart data elements available to health care providers to be imported into progress notes and to be viewed as a flowsheet. Automated reporting of WVS data elements were used to assess adherence to clinical care guidelines. SS/Sβ0 patients should generally have an office visit every 90 days. Our analysis indicated that 27% of patients (36/134) had not had an office visit in > 120 days. We also noted deficiencies in immunization in patients age 2 years and older: 9% (12/134) Pneumococcal 23, 20% (26/134) Prevnar 13, and 30% (40/134) meningococcal. In some cases these deficiencies were in documentation only. Among 106 TCD eligible patients, 8% (8/106) are not up to date. Discussion Providers and families need to track a vast number of data elements throughout the lifespan of a child with a chronic disease. AE reporting can define illness severity at an individual level and identify cohorts within the population experiencing more frequent and severe complications. Ultimately, this type of analysis will identify SCD patients who could benefit from therapeutic interventions such as Hydroxyurea, chronic transfusion or transplant. Automated reports generated from the smart data elements in the WVS permit focused efforts targeting adherence to health maintenance needs. This project highlights the utility of enhanced granular data entry in the EHR to inform clinical and research decision making for individuals and populations. Supported by the NGMS of the NIH under Award Number P20GM109021. Disclosures No relevant conflicts of interest to declare.

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Creary, Susan E., Mark T. Gladwin i Lakshmanan Krishnamurti. "Mobile Directly Observed Therapy: Monitoring and Improving Hydroxyurea Adherence in Pediatric Sickle Cell Patients". Blood 120, nr 21 (16.11.2012): 2060. http://dx.doi.org/10.1182/blood.v120.21.2060.2060.

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Abstract Abstract 2060 Sickle cell disease (SCD) is a serious inherited red blood cell disorder that results in significant morbidity and premature mortality. Hydroxyurea (HU) is an efficacious medicine that reduces pediatric SCD complications, but poor medication adherence is common and limits effective HU utilization. Directly observing therapy (DOT) involves healthcare workers traveling to observe medication ingestion and it is a successful strategy used for anti-tuberculosis therapy. While DOT has the potential to improve adherence to chronic medications such as HU, high cost, inconvenience, and intrusiveness limit this strategy. We hypothesize that a modified version of DOT which uses mobile phones and computers (Mobile DOT), is feasible, can improve adherence, and is acceptable to patients and caregivers. Patients with SCD were eligible for this 6-month pilot study if they were 1–22 years old, prescribed HU for ≥6 months, and had daily access to a mobile phone or computer capable of recording and submitting videos. Mobile DOT participants record a daily video of their HU administrations with their phone or computer and submit these videos to a secure website for review. It does not require custom hardware or software. Participants receive automated daily reminder electronic messages. They are called to encourage adherence when needed and to provide them with technical support. Participants receive token monetary compensation when they meet adherence goals and complete surveys. To measure adherence, this study used the Morisky Medication Adherence Scale (MMAS-4, score range 0–4), the medication possession ratio (MPR) calculated from prescription refill records, laboratory markers including hemoglobin F percentage (HgbF) and mean corpuscular volume (MCV) that increase with HU therapy, and direct observation. Participants completed the Abbreviated Treatment Satisfaction for Medication survey (TSQM-9) and a 12-question survey to measure satisfaction with HU and Mobile DOT respectively. Investigators discussed this study with 19 prospective participants and 15 enrolled. Mean participant age was 13.7 years (SD ± 6.3 years, range 4–21 years). One participant withdrew because he lost computer access. Videos were approximately 10–30 seconds long and an investigator performed the observations, tracking, and phone calls in <1 hour each day. Most participants had Hemoglobin SS disease (n=11) and took HU for frequent pain crises (n=7) or acute chest syndrome (n=6). At enrollment, mean MMAS-4 score was 2.0 (SD ± 0.4), indicating moderate self- reported adherence. MPR was 67% (SD ± 26%, range 18–100%). Laboratory markers indicated good adherence (MCV>100fL and HgbF>15%) in 3 participants, moderate adherence (MCV≥90fL and HgbF>12%) in 4 participants, and poor adherence (MCV<90fL or HgbF<12%) in 7 participants. The TSQM-9 survey showed participants had 79.5% (SD ± 20.4%) global HU satisfaction rate, they felt HU was 76.2% (SD ± 22.2%) effective, and they felt taking HU was 81.7% (SD ± 16.4%) convenient. To date, all participants completed ≥30 days of the study. Direct observation showed that mean adherence was 92.1% (SD ± 0.7%, range 76–100%) at 30 days. Seven participants thus far have completed ≥2 months on study and have additional survey and laboratory data. Mean adherence in these patients was 90.5% (SD ± 6%, range 80–100%) at 60 days. MMAS-4 scores decreased from 2.1 (SD ± 0.4) to 1.3 (SD ± 1.1), suggesting improved adherence. Laboratory markers also showed improved adherence trends. Mean MCV increased from 94.3fL (SD ± 4.2fL) to 101.2fL (SD ± 8.3fL) and mean HgbF increased from 10.0% (SD ± 5.6%) to 11.3% (SD ± 4.7%). Mobile DOT surveys showed that participants found Mobile DOT easy to use, took <5 minutes each day, helped remind them to take HU, and did not invade their privacy. These results suggest that Mobile DOT is a feasible way to monitor and improve HU adherence in patients with pediatric SCD. Patients were willing to enroll on the study and surveys suggest that participants find Mobile DOT to be convenient, non-intrusive, and an acceptable. This strategy is potentially easy to disseminate because it does not include additional hardware or programming and requires minimal staff support. A larger clinical trial is needed to determine if long term Mobile DOT can impact clinical outcomes in pediatric SCD. Disclosures: No relevant conflicts of interest to declare.

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"CARPENTER PROJECT 70+ CUSTOM 630". Alloy Digest 52, nr 6 (1.06.2003). http://dx.doi.org/10.31399/asm.ad.ss0886.

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Abstract Carpenter Project 70+ Custom 630 is a modified version of conventional stainless steel Type 630 (17Cr-4Ni) with improved machinability. The alloy has good fabrication characteristics and can be age hardened by a single-step, low-temperature treatment. See also Carpenter Custom 630, Alloy Digest SS-258, revised December 2000, and Carpenter Project 70 Stainless Custom 630, Alloy Digest SS-732, November 1998. This datasheet provides information on composition and physical properties. It also includes information on forming, heat treating, machining, and joining. Filing Code: SS-886. Producer or source: Carpenter Specialty Alloys.

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"CARPENTER CUSTOM 465". Alloy Digest 47, nr 5 (1.05.1998). http://dx.doi.org/10.31399/asm.ad.ss0716.

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Abstract Carpenter Custom 465 stainless steel is an age-hardenable martensitic alloy with less sensitivity to process parameters than other similar alloys. It develops high strength along with fracture toughness and resistance to stress-corrosion cracking. This datasheet provides information on composition, physical properties, hardness, elasticity, and tensile properties as well as fatigue. It also includes information on corrosion resistance as well as forming and heat treating. Filing Code: SS-716. Producer or source: Carpenter.

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"CARPENTER CUSTOM 630". Alloy Digest 49, nr 12 (1.12.2000). http://dx.doi.org/10.31399/asm.ad.ss0258.

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Abstract Carpenter Custom 630 is a martensitic precipitation (age) hardening (PH) stainless steel offering high strength and hardness along with excellent corrosion resistance. It has good fabricating characteristics and can be age hardened by a single-step, low-temperature treatment. This datasheet provides information on composition, physical properties, hardness, elasticity, and tensile properties as well as fracture toughness and creep. It also includes information on high temperature performance and corrosion resistance as well as forming, heat treating, machining, and joining. Filing Code: SS-258. Producer or source: Carpenter. Originally published August 1971, revised December 2000.

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"CARPENTER CUSTOM FLO 316HQ". Alloy Digest 54, nr 10 (1.10.2005). http://dx.doi.org/10.31399/asm.ad.ss0944.

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Abstract Carpenter Custom Flo 316HQ is modified from the base alloy type 316 stainless steel by the addition of copper and the lowering of carbon content in order to develop an alloy with corrosion resistance and minimum work hardening upon cold work. This datasheet provides information on composition, physical properties, and tensile properties. It also includes information on corrosion resistance as well as forming, heat treating, machining, and joining. Filing Code: SS-944. Producer or source: Carpenter Specialty Alloys.

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