cssi/SciSciGPT-SciSciNet huggingface dataset:
Comorbidity Measures In Ex Vivo T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

Clinical comorbidity measures enhance the estimates of HCT tolerance and outcomes, thereby aiding therapeutic decisions. Ex vivo T cell depletion (TCD) of the graft reduces the risk of graft-versus-host disease and improves the tolerability of allogeneic transplantation in patients with impaired pretransplant performance. However, prediction tools such as the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), have only been validated in conventional T-replete HCT. To improve outcome prediction in TCD transplants we therefore evaluated published comorbidity measures and other potential biomarkers of outcome in a series of myeloablative TCD transplant recipients. Pre transplant (week -2) factors measured were: HCT-CI, ECOG performance status, serum C-reactive protein (CRP), albumin (ALB), pre-albumin (PAB), ferritin, absolute lymphocyte counts (ALC), and absolute lymphocyte / monocyte ratio (LMR). CRP was also studied serially post transplant. CRP increased after conditioning, peaked (p =0.0001) in the first week of HCT, with recovery to baseline at 5 weeks post-HCT. We evaluated outcomes in a cohort of 79 patients in our institute with hematological malignancies receiving myeloablative total-body irradiation, and an HLA-identical sibling peripheral blood HCT, T cell depleted using Miltenyi CD34+ selection. The median age of recipients was 43 years (range 13-68 years). Of the 79, 34 (43%) had standard risk disease, and 45 (57%) recipients had high-risk disease. At a median follow up of ∼ 5 years, overall survival (OS) was 42.9% and nonrelapse mortality (NRM) was 33.9%. Comorbidity measures were first screened to eliminate highly-correlated covariates. Univariate Cox regression models were used to identify significant factors (p 0 were found to be significantly associated with the cumulative incidence of relapse (both p=0.01). In conclusion, this is the first study to explore comorbidity scores and biomarkers to predict outcome after ex vivo TCD HCT. Our results suggest that HCT-CI score, preCRP, postCRP and the LMR are important independent clinical predictors of OS and NRM in TCD HCT. Disclosures: No relevant conflicts of interest to declare.
Geobiology and palaeogenomics

Abstract Geobiology is centered on interactions of the biosphere with the atmosphere, hydrosphere, and lithosphere. In deep time geobiology has focused on critical intervals of change for Earth and its biota. Such geobiological studies include data from palaeobiology, geochemistry and sedimentary geology within an interdisciplinary framework. Palaeogenomics has a variety of research agendas, and one of them is to understand the genes involved in key changes in the evolutionary history of life and when those genes and their interactions first evolved. The combination of geobiology and palaeogenomic studies is a powerful approach which leads to a more fundamental understanding of how Earth and life have changed through time. For example, linking palaeogenomic studies of biomineralization genes in modern organisms and when they first evolved in the Cambrian with geobiological studies of the impact this had on the production of carbonate sedimentary facies such as encrinites and the development of the Neritan ocean provides a unique perspective on how genes have shaped formation of the sedimentary record. Another component of the Cambrian explosion, the evolution of vertical bioturbation at the start of the Cambrian, has had significant effects on biogeochemical cycling and sediment production, and provides an inviting target for future genomic studies. The remaining Phanerozoic includes a broad variety of evolutionary innovations which within a joint geobiological and palaeogenomic context can also be profitably studied. In pelagic environments the genomic changes leading to evolution of the calcium carbonate biomineralized skeletons of coccolithophores contributed to the widespread deposition of carbonate sediment in deep settings and development in the Mesozoic of the Cretan ocean. On land, linking palaeogenomic studies of the genes that led to the Palaeozoic evolution of lignin and their associated geobiological effects, such as deposition of coal, provide another example of the effects of genes upon development of the sedimentary record. Such work will ultimately provide a history of genomic change and the environmental factors that influenced it, as well as how genomic change influenced environments.
Short History of the Relation Between Mathematics and Music

This chapter is a short overview of some important persons and movements in the history of the interaction of mathematics and music. It is far from complete, but should give the reader a first impression of this traditional and deeply “mathemusical” culture.
Should US Physicians Support the Decriminalization of Commercial Sex

The Nordic model policy option for addressing commercial sex—which exempts sellers from criminal penalties—offers several potential advantages.
Using the Equity Residual Approach to Valuation: An Example

This note provides a detailed explanation of how to apply the equity residual valuation method when the debt/equity mix is changing. An example is provided that works through levering betas. The note can be used to accompany cases on leveraged buyouts.
Flight Management Procedures for Noise-minimal Landing Trajectories with Consideration of Temperature and Wind Gradients

Abstract The future world-wide installation of the newly developed Microwave Landing System (MLS) will permit a four-dimensional (incl. time) guidance of aircraft in the airport area with the combined advantages of safer, more economical flight paths with less detrimental environmental impact such as noise nuisance. Purpose of this paper is to demonstrate that the introduction of these advanced navigation and flight guidance technologies will make it possible to compute and to apply continuously time-dependent command inputs for an aircraft in a way which will minimize the noise annoyance for the population living in the neighborhood of the airport. Factors considered in the investigations for the optimization calculations included not only the location and population density of living areas along the approach trajectory but also the effects of temperature and wind gradients on noise propagation. The results obtained for the Airport Dusseldorf-Lohausen show that, even taking into account numerous design, comfort, and safety constraints, the noise exposure for the average airport area inhabitant could be reduced by 70 % if the proposed flight trajectory management procedure would be applied.
Disparities in the Use of Diabetes Screening in Appalachia

Purpose The Appalachian region presents disproportionately high rates of chronic disease compared to the rest of the United States. Early diagnosis of diabetes through screening is an important step in reducing diabetes complications. This study examines disparities in the use of diabetes screening in Appalachia. Methods We analyzed 2009 and 2010 Behavioral Risk Factor Surveillance System data for 96,111 adults aged ≥45 years from 11 Appalachian states. Based on economic status, Appalachian counties were grouped into distressed (least affluent), at-risk, transitional, and competitive (most affluent). Logistic regression analyses were used to estimate the statistical significance and effect size of factors associated with diabetes screening. Results Competitive counties had the highest rate of diabetes screening (65.4%). At-risk counties had the lowest rate (60.3%), about 7.8% lower compared to competitive counties (P < .001). After adjusting for socioeconomic factors, differences in screening rates between county economic levels in Appalachia were not statistically significant. Among respondents ≥65 years, at-risk counties had an 8.1% lower screening rate compared to competitive counties; this difference was not adequately explained by differences in socioeconomic factors. Screening rates in distressed and transitional counties were not significantly different from competitive counties in unadjusted or adjusted models. Conclusions At-risk counties had significantly lower screening rates than competitive counties. They should receive more policy attention similar to that received by distressed counties. Social policies that improve socioeconomic status and educational attainment, and health policies that reduce barriers to access to care may reduce disparities in diabetes screening rates in the less affluent Appalachian counties.
Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n = 10) or pure GBM (n = 34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P 0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.
Predictive analytics for learning and usage of the plant sciences E-library

This study examines learning and usage of the Plant Sciences E-Library (PASSEL, passel.unl.edu), a large international, open-source multidisciplinary learning object repository (7793 users from 14 countries). The analyses employ predictive analytics to isolate usage variables which predict learning from the instructional material. Specifically, the study focuses on student engagement as measured by total time online and time spent with different content modality material. This paper describes the analytic process, reports data on usage of learning object modules and module elements, identifies significant predictors of learning, and discusses future research directions.
Effect of the Topical Repellent para-Menthane-3,8-diol on Blood Feeding Behavior and Fecundity of the Dengue Virus Vector Aedes aegypti

Dengue fever is an acute disease caused by the dengue virus and transmitted primarily by the mosquito Aedes aegypti. The current strategy for dengue prevention is vector control including the use of topical repellents to reduce mosquito biting. Although N,N-diethyl-m-methylbenzamide (DEET) is the most common active ingredient in topical repellent products, para-menthane-3,8-diol (PMD) is also used commercially. Studies have indicated PMD reduced biting by 90–95% for up to 6–8 h, similar to the efficacy of DEET, depending on the testing environment. The purpose of this study was to evaluate the behavioral effects of PMD on Ae. aegypti blood feeding and fecundity to explore the potential impact of PMD on downstream mosquito life-history traits. Two experiments were performed. In both experiments, cohorts of female Ae. aegypti (Belize strain) were exposed to 20% PMD or ethanol for 10 min in a closed system and introduced to an artificial membrane feeding system. Following a 30min feed time, mosquitoes of Experiment 1 were killed and weighed as a proxy measure of blood meal, whereas mosquitoes of Experiment 2 were monitored for oviposition, a measure of fecundity. Results showed a statistically significant reduction (p < 0.001) in the percentage of Ae. aegypti that blood-fed when exposed to PMD (38%) compared to those non-exposed (49%). No significant difference in fecundity between test populations was indicated. These findings suggest that exposure of Ae. aegypti to 20% PMD may influence the probability of subsequent blood feeding but of those mosquitoes that do blood feed, egg-lay density is not affected. Further studies are warranted to investigate the full range of effects of PMD exposure on other Ae. aegypti life-history traits such as mating, to continue characterizing the potential effects of PMD to impact overall vector population dynamics.
STATISTICAL TESTS OF HYPOTHESES–GENERAL AND ONE SAMPLE

This chapter discusses statistical tests of hypotheses. It focuses on significance testing and describes drawing inferences about populations from observed samples. Significance tests discussed in the chapter are concerned with decisions on parameters rather than decisions on the type of population. For the normal population, the parameters are μ and α , while for the binomial and Poisson, they are Φ and μ , respectively. The chapter describes two approaches that may be used. The null hypothesis value of the parameter, the sample size, and the α risk may be set. Then the OC curve may be sketched and whether it gives a good balance between sampling costs and n versus protection against wrong decisions may also be seen. If not, then one must adjust n and/or α. The second approach is to set two levels of the parameter in question and corresponding α and β risks and then find the needed sample size and critical value for the statistic to be used. Thus, in this case, two points on the OC curve are specified.
Ternary Feldspar/Melt Equilibria: A Review

The compositions of ternary feldspars coexisting in equilibrium with melts are constrained by the subsolidus characteristics in the system Ab-An-Or. The presence of a solvus in the ternary feldspar system indicates that there is limited solubility of the three components at magmatically reasonable temperatures and pressures. The shape of the solvus in T-X space indicates that this solubility increases significantly with temperature but only slightly with pressure, thereby laying the foundation for ternary feldspar geothermometry. Several thermodynamic models describing the mixing behavior of components in ternary feldspars have been developed for use in geothermometry. However, because of the paucity of data at high temperatures and in Ab-poor regions, there are significant variations in the predicted high-temperature characteristics of the solvus. Nonetheless, when combined with models for silicate melts in the feldspar system, most of the models for the solid solutions yield the same general trends in compositional evolution of feldspars during crystallization or melting (although the specific temperatures and pressures at which various changes in behavior are manifested vary with the model chosen). The major differences between the evolutionary histories of ternary feldspars undergoing equilibrium or fractional crystallization at high or low temperatures and under H2O-unbuffered or H2O-buffered conditions provide important criteria for the interpretation of the histories of natural igneous rocks.
Solubilization, Purification and Properties of Membrane-Bound Brain Enzymes which Biosynthesize Phosphoinositides

For some years, evidence has steadily accumulated that cellular inositol phospholipid metabolism is stimulated in response to hormones or neurotransmitters in a variety of tissues. These are now generally considered to be receptor-mediated, cyclic AMP-independent phenomena which involve an initial accelerated breakdown of one or more of the phosphoinositides followed by their resynthesis. The nature of the molecular linkage between receptor activation, stimulated phosphoinositide degradation and subsequent cellular events, such as mobilization of cytosolic Ca 2+ or liberation of arachidonic acid as precursor to prostaglandin formation, has become a significant problem in membrane biochemistry and is discussed in another chapter in this volume (Hauser 1983).
Exact system relationships

The verification problem for a system S a and a model of desired behavior S b , asks the fundamental question of whether S a is either equivalent to the desired system \((S_a \cong S_b)\) or contained in the desired system \((S_a \preceq S_b)\). The answer to such questions will always depend on what we mean by system equivalence and system containment. In this chapter, we give various precise de_nitions for such relationships between two systems.
RELAP4 analysis of the loss-of-coolant transients for a low pressure/low temperature research reactor

The RELAP4 computer program has been used to study loss-of-flow and loss-of-coolant transients for the University of Missouri Research Reactor (MURR). Simple experimental tests have been conducted to provide RELAP4 model parameters. The computer results have provided an understanding of MURR behavior under accident conditions, and may also be useful in understanding the low pressure/low temperature range of transients at other reactors.
High-pressure single-crystal X-ray diffraction and synchrotron Mössbauer study of monoclinic ferrosilite

Abstract The phase and spin transitions in single-crystal monoclinic ferrosilite, FeSiO3, were investigated using X-ray diffraction and Mossbauer spectroscopy up to lower-mantle pressures and room temperature in a helium pressure medium. Using single-crystal X-ray diffraction, we measured the equation of state of ferrosilite up to about 43 GPa. We observed a P21/c-to-C2/c phase transition between 1.5 and 1.7 GPa and a phase transition from C2/c to a distinct P21/c structure between 30 and 34 GPa. With time-domain Mossbauer spectroscopy, we determined the hyperfine parameters of ferrous iron up to 95 GPa. The phase transitions were correlated with discontinuities in Mossbauer spectral features. We observed the onset of high-spin-to-low-spin transitions in the M1 and M2 sites at ∼37 GPa and ∼74 GPa, respectively. Understanding the electronic structure of iron in a well-characterized single crystal of ferrosilite may help interpret the behavior of iron in complex dense silicate phases.
Quantifying the effects of head movement on magnetic resonance spectroscopy estimates of gamma-aminobutyric acid

There has been keen interest in measuring in vivo GABA. However, GABA signal is low and typically measured using techniques vulnerable to the confounding effects of in-scanner head movement. This issue is particularly problematic for clinical studies since it may lead to Type I or II error in testing for group differences. While solutions to mitigate the effects of movement have been proposed, fundamental and largely unexamined issues are the nature and scale of this effect. We developed a method to quantify and characterize head movement during GABA spectroscopy and found that two parameters of movement, displacement and instantaneous movement, were inversely correlated with and accounted for 12.1% and 20.2% variance of GABA estimates respectively. We conclude that head movement can significantly affect GABA measurements and the application of methods to account for movement may improve of GABA measurement accuracy and the detection of true group differences in clinical studies.
Temporal and spatial dynamics of fish community structure during watershed alteration in two Ouachita River systems

Fish community composition is highly dynamic, but generally exhibits loose equilibrium within bounds of community structure in upland stream systems with minimal anthropogenic disturbance. Chronic anthropogenic disturbance can exceed ecological thresholds and shift fish community composition to an alternative state. Therefore, long‐term datasets are critical to understand spatiotemporal dynamics of fish community structure. We quantified temporal changes in fish communities in two Ouachita River systems during watershed alteration (i.e., development and reservoir construction) using a suite of multivariate and univariate analyses to assess changes in fish community structure and taxonomic and functional β‐diversity. We found fish community composition shifted in the Saline River basin possibly in response to human disturbance (e.g., development) and hydrologic variability. Furthermore, functional homogenisation occurred through time. In the Ouachita Headwaters basin, taxonomic homogenisation was evident and two fluvial specialists were not detected during the current period. Taxonomic and functional β‐diversity patterns were not consistent across basins demonstrating the complexity of biotic homogenisation. Our retrospective analyses showed human activities played a role in restructuring fish communities despite minimal invasion of exotic species. Ultimately, our study characterised fish community structure across snapshots of time and demonstrates the importance of increasing the frequency of sampling intervals and continuing long‐term collections with similar methods to enhance the understanding of community dynamics.
Diastereoselective one-pot synthesis of 7- and 8-substituted 5-phenylmorphans.

Novel 7- and 8-alkyl and aryl substituted 5-phenylmorphans were synthesized from substituted allyl halides and N-benzyl-4-aryl-1,2,3,6-tetrahydropyridine by a highly efficient and diastereoselective reaction series, “one-pot” alkylation and ene-imine cyclization followed by sodium borohydride reduction. Mild cyclization conditions gave the desired substituted 5-phenylmorphans in good yield as a single diastereomer.
Evaluations of Prevention Programs for Sexual, Dating, and Intimate Partner Violence for Boys and Men: A Systematic Review:

Among violence prevention educators and researchers, there is growing interest in sexual, dating, and intimate partner violence (SV/DV/IPV) prevention programs for males because of evidence showing that boys and men are more likely than girls and women to perpetrate SV as well as more severe forms of DV/IPV. To date, comprehensive guidance on the content, structure, delivery, and effectiveness of such programs is limited. We reviewed randomized controlled studies that evaluated SV/DV/IPV perpetration prevention programs for boys and men. Searches yielded 5,249 potential documents for review of which 10 met inclusion criteria-representing 9 unique studies of 7 distinct programs. Two reviewers independently reviewed and abstracted data from these studies regarding program setting and target audience; type of violence addressed; number and length of program sessions; program duration, topics, activities, and delivery mode; and implementer details. Study characteristics were also examined (sample size, participant characteristics, recruitment, randomization, comparison/control condition, data collection protocols, attrition, measures of violence perpetration, and perpetration findings). The Cochrane Risk of Bias Tool was used to assess study design quality. Results show considerable heterogeneity among program content and delivery strategies, study designs, and outcome measurement. Study sample size ranged widely, and most used cluster-randomized designs, recruited undergraduate college students, and evaluated a multisession program delivered via group sessions. Only one program reduced men's self-reported SV perpetration. Accordingly, critical gaps exist around "what works" for SV/DV/IPV perpetration prevention programs for boys and men.
From 1965 to 2018: What Happened to Black Men?

In 1965, there were a number of major events occurring in the United States, including the U.S. soldiers fighting in the Vietnam War; the historic march that took place in Selma, Alabama, led by Dr. Martin Luther King, Jr.; the murder of Malcom X in Harlem, New York; and the signing of The Voters Rights Act by President Lyndon B. Johnson. It was a time that Black families were moving in a positive direction in the areas of housing, employment, and education. Since 1965, Black men in the United States have not made the same progress as their White and Hispanic counterparts. This article explores both the absence of Black males in households as well as the nesting syndrome created by mothers rearing Black men and its impact on Black males since 1965.
Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway.

In meiosis, multiple different DNA sequence motifs help to position homologous recombination at hotspots in the genome. How do the seemingly disparate cis-acting regulatory modules each promote locally the activity of the basal recombination machinery? We defined molecular mechanisms of action for five different hotspot-activating DNA motifs (M26, CCAAT, Oligo-C, 4095, 4156) located independently at the same site within the ade6 locus of the fission yeast Schizosaccharomyces pombe. Each motif promoted meiotic recombination (i.e., is active) within this context, and this activity required the respective binding proteins (transcription factors Atf1, Pcr1, Php2, Php3, Php5, Rst2). High-resolution analyses of chromatin structure by nucleosome scanning assays revealed that each motif triggers the displacement of nucleosomes surrounding the hotspot motif in meiosis. This chromatin remodeling required the respective sequence-specific binding proteins, was constitutive for two motifs, and was enhanced meiotically for three others. Hotspot activity of each motif strongly required the ATP-dependent chromatin remodeling enzyme Snf22 (Snf2/Swi2), with lesser dependence on Gcn5, Mst2, and Hrp3. These findings support a model in which most meiotic recombination hotspots are positioned by the binding of transcription factors to their respective DNA sites. The functional redundancy of multiple, sequence-specific protein–DNA complexes converges upon shared chromatin remodeling pathways that help provide the basal recombination machinery (Spo11/Rec12 complex) access to its DNA substrates within chromatin.
An unusual presentation of ACE inhibitor-induced visceral angioedema

ACE inhibitors (ACEi) are common anti-hypertensive drugs that can cause angioedema. Though classic, or facial angioedema is rare, visceral angioedema is even less common. When angioedema occurs, it typically presents early, within 30 days of initiating therapy. Visceral angioedema most commonly presents with nausea, emesis, abdominal pain and diarrhoea, and thus is often mistaken for an episode of gastroenteritis. When a CT scan is obtained, it typically shows characteristic findings, including ascetic fluid, mild mesenteric oedema and thickening of the small bowel. In this case report, we present a patient who did not experience her first episode of visceral angioedema until after she had been on ACEi therapy for 5–7 years. In addition, she experienced recurrent episodes of visceral angioedema that were separated by approximately 4 years at a time. Both of these features make for a particularly unique presentation.
Faith in formaldehyde: conversion in the oldest cabinet of curiosity in the Philippines

This paper examines the oldest existing museum in the Philippines, the University of Santo Tomas Museum of Arts and Sciences, as a cabinet of curiosity and a catalyst of conversion. By Spanish roya...
The Binocular Ver

Although the visual evoked response (VER) is frequently used to assess binocularity, the contribution of the monocular components to the binocular VER is poorly understood. In a typical binocular situation, both eyes view the same stimulus pattern and the amplitude of the binocular VER is approximately 1.4 times larger than the amplitude of either monocular response. This parallels psychophysical reports of binocular brightness and contrast summation. We have examined checkerboard (14’ checks) pattern-reversal (3.75 Hz) VERs evoked from observers with normal binocularity using conditions in which interocular luminance differences (from 0.0 to 2.0 log units) were established. We found that for luminance differences up to 0.6 log units, the amplitude of the binocular VER did not vary significantly. Larger luminance differences resulted in decreased amplitudes with luminance differences between 1.3 and 2.0 log units resulting in amplitudes significantly smaller than the amplitude of either monocular VER. These results imply some type of inhibitory binocular interaction. Furthermore, observers with anomalous binocularity exhibited deviations from this normal pattern.
2D-FFTLog: efficient computation of real-space covariance matrices for galaxy clustering and weak lensing

Accurate covariance matrices for two-point functions are critical for inferring cosmological parameters in likelihood analyses of large-scale structure surveys. Among various approaches to obtaining the covariance, analytic computation is much faster and less noisy than estimation from data or simulations. However, the transform of covariances from Fourier space to real space involves integrals with two Bessel integrals, which are numerically slow and easily affected by numerical uncertainties. Inaccurate covariances may lead to significant errors in the inference of the cosmological parameters. In this paper, we introduce a 2D-FFTLog algorithm for efficient, accurate and numerically stable computation of non-Gaussian real space covariances for both 3D and projected statistics. The 2D-FFTLog algorithm is easily extended to perform real space bin-averaging. We apply the algorithm to the covariances for galaxy clustering and weak lensing for a Dark Energy Survey Year 3-like and a Rubin Observatory's Legacy Survey of Space and Time Year 1-like survey, and demonstrate that for both surveys, our algorithm can produce numerically stable angular bin-averaged covariances with the flat sky approximation, which are sufficiently accurate for inferring cosmological parameters. The code CosmoCov for computing the real space covariances with or without the flat sky approximation is released along with this paper.
STudy of Alteplase for Respiratory failure in SARS-Cov2/COVID-19: Study Design of the Phase IIa STARS Trial.

Background: The COVID-19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID-19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow-up trial using the widely available tissue-plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective: To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods: A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO2 ratio 4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re-dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results: The primary outcome is improvement in PaO2/FiO2 at 48 hours post-randomization. Other outcomes include: ventilator- and ICU-free-days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped-wedge design with four looks at the data. Conclusion: Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634).
The Bildung Subject and Modernist Autobiography in An Béal Bocht (Beyond An tOileánach)

Brian O Conchubhair examines An Beal Bocht as a modernist reinvention of the traditional Bildungsroman novel. By demonstrating how An Beal Bocht simultaneously plays with the conventions of the Gaeltacht Bildungsroman and deploys modernist invention, O Conchubhair demonstrates the importance of including An Beal Bocht in those critical conversations which laud O’Nolan’s English-language works for their literary radicality. In this context, An Beal Bocht is positioned as a text which, through a series of inversions and reinventions of the tropes of the Bildungsroman novel, sheds a ‘light on the warped nature of Irish society and cultural politics in the interwar years’ by tearing down the ideologically constructed notion of cultural identity and uncovering ‘the gap between lived reality and imagined experience.’
Forecasting Atmospheric Visibility Using Auto Regressive Recurrent Neural Network

Atmospheric visibility conditions not only affect traffic on roads, but also aviation operations. Poor visibility at the destination site can reduce airport capacity leading to ground delays, flight cancellations, flight diversions, and extra operating costs. Hence, timely forecast of visibility is important for safe operation in both airports and highways. Visibility is affected by meteorological weather variables such as precipitation, temperature, wind speed, humidity, smoke, fog, mist, and Particulate Matter (PM) concentrations in the atmosphere. This paper is an effort to forecast univariate weather variable visibility and explore the effect of highly correlated meteorological weather variables on visibility, using an Auto Regressive Recurrent Neural Network (ARRNN). By adjusting the number of epochs and the regression horizon, i.e. past time steps used in visibility prediction, we showed that ARRNN outperforms long-short term memory (LSTM) networks and vanilla recurrent neural network (Vanilla RNN) in terms of coefficient of determination (R2).
Assessing the Role of Projections from the Ventral Hippocampus (vHIP) to the Medial Prefrontal Cortex (mPFC) in the Neural Circuitry of Social Familiarity-induced Anxiolysis (SoFiA) using Gi-DREADDs

The social interaction habituation (SI-hab) protocol has been used to demonstrate that rats acquire Social Familiarity-induced Anxiolysis (SoFiA), a form of safety learning where rats display anxiolysis in the presence of a familiar conspecific. SoFiA acquisition and expression can be simplified into four different constructs: social memory, anxiety, safety learning and anxiolysis. The neural circuitry of SoFiA; however, has not been fully identified. As a step towards elucidating the SoFiA neural circuitry we are identifying the role of projections from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) in SoFiA acquisition. Prior work from our lab has shown that the mPFC is needed for acquisition and expression of SoFiA. The mPFC may be the location of convergence of anxiety and social memory processing, making it a loci for safety learning. The goal of the current work is to identify the inputs to the mPFC that are pivotal for SoFiA acquisition. vHIP has been implicated in social memory and projects to the mPFC leading to the hypothesis that SoFiA acquisition requires vHIP projections to mPFC. This hypothesis will be tested via intersectional genetics where neural tracts are selectively targeted through viruses. One virus is introduced at the soma of the neuron, and another is introduced at the end of the axon. The first virus, adeno-associated virus 8 (AAV8) will contain Cre-dependent code for an inhibitory DREADD (designer receptors exclusively activated by designer drugs.) The second virus, canine adenovirus 2 (CAV2) is picked up by axon terminals and transported to the soma where it will express Cre. Unfortunately, the uptake and transport of these viruses require specific receptors and the vHIP-mPFC pathway has poor CAV2 uptake. CAV2 levels will be increased by the introduction of Coxsackievirus and Adenovirus receptor (CAR) via AAV8 two weeks prior to CAV2-Cre injection.
Feedforward mechanisms of masking in mouse V1

Abstract Sensory neurons not only encode stimuli that align with their receptive fields but are also modulated by context. For example, the responses of neurons in mouse primary visual cortex (V1) to gratings of their preferred orientation are modulated by the presence of superimposed orthogonal gratings (“plaids”). The effects of this modulation can be diverse: some neurons exhibit cross-orientation suppression while other neurons have larger responses to a plaid than its components. We investigated whether these diverse forms of masking could be explained by a unified circuit mechanism. We report that the suppression of cortical activity does not alter the effects of masking, ruling out cortical mechanisms. Instead, we demonstrate that the heterogeneity of plaid responses is explained by an interaction between stimulus geometry and orientation tuning. Highly selective neurons uniformly exhibit cross-orientation suppression, whereas in weakly-selective neurons masking depends on the spatial configuration of the stimulus, with effects transitioning systematically between suppression and facilitation. Thus, the diverse responses of mouse V1 neurons emerge as a consequence of the spatial structure of the afferent input to V1, with no need to invoke cortical interactions.
Evaluating CUDA Portability with HIPCL and DPCT

HIPCL is expanding the scope of the CUDA portability route from an AMD platform to an OpenCL platform. In the meantime, the Intel DPC++ Compatibility Tool (DPCT) is migrating a CUDA program to a data parallel C++ (DPC++) program. Towards the goal of portability enhancement, we evaluate the performance of the CUDA applications from Rodinia, SHOC, and proxy applications ported using HIPCL and DPCT on Intel GPUs. After profiling the ported programs, we aim to understand their performance gaps, and optimize codes converted by DPCT to improve their performance. The open-source repository for the CUDA, HIP, and DPCT programs will be useful for the development of a translator.
Validity of remote administration of the MATRICS Consensus Cognitive Battery for individuals with severe mental illness

Abstract The MATRICS Consensus Cognitive Battery (MCCB) is a gold-standard tool for assessing cognitive functioning in individuals with severe mental illness. This study is an initial examination of the validity of remote administration of 4 MCCB tests measuring processing speed (Trail Making Test: Part A, Animal Fluency), working memory (Letter-Number Span), and verbal learning and memory (Hopkins Verbal Learning Test-Revised). We conducted analyses on individuals with bipolar disorder (BD) and schizophrenia-spectrum disorders (SCZ), as well as healthy volunteers, who were assessed in-person (BD = 80, SCZ = 116, HV = 14) vs. remotely (BD = 93, SCZ = 43, HV = 30) to determine if there were significant differences in performance based on administration format. Additional analyses tested whether remote and in-person assessment performance was similarly correlated with symptom severity, cognitive and social cognitive performance, and functional outcomes. Individuals with BD performed significantly better than those with SCZ on all MCCB subtests across administration format. Animal Fluency did not differ by administration format, but remote participants performed significantly worse on Trail Making and HVLT-R. On the Letter-Number Span task, individuals with bipolar disorder performed significantly better when participating remotely. Finally, patterns of correlations with related constructs were largely similar between administration formats. Thus, results suggest that remote administration of some of the MCCB subtests may be a valid alternative to in-person testing, but more research is necessary to determine why some tasks were affected by administration format.
A New Way of Thinking: The Essentials of Nonviolent Living

This thought, stated by Albert Einstein, in 1946, is of course, referring to the threat of nuclear annihilation that has grown ever more dangerous in the last 42 years. War and violence was a practical, feasible solution (albeit undesireable from a philosophical and humanistic point of view) to disputes in other, older periods of our history. As a species, we have been unable to move to a new way of thinking in which nonviolence is a basic and unchallengeable characteristic.
Cayley factorization and a straightening algorithm

An important problem in computer-aided geometric reasoning is to automatically find geometric interpretations for algebraic expressions. For projective geometry this question can be reduced to the Cayley factorization problem. Before describing this problem, we give a brief introduction to the Cayley algebra for those readers not already familiar with it. The Cayley algebra is essentially the same as the classical Grassmann algebra. This algebra provides projectively invariant algebraic interpretations of synthetic geometric statements. A more thorough exposition may be found in Barnabei et al. (1985), Doubilet et al. (1974), or Rota & Stein (1976).
Yakity‐Yak: Who Talks Back? An Email Experiment

Objective. We extend the scope of the often-asked question “who talks more—men or women?” by analyzing gender differences in talking via electronic communication. We do this by conducting a controlled experiment to elicit email communications and personal characteristics from a sample of college students. Methods. An integration of the disparate fields of communications, education, women's studies, and economics guides our approach, which uses multivariate regression to explain word counts from our electronic survey. Results. We find a positive and significant effect of being female on number of words used, especially when communication is with a female professor, consistent with a female role model hypothesis. Conclusion. Overall, we find that women “talk” more than men—sometimes. The results depend on the topic of conversation and to whom they are talking. Electronic communications may level the playing field, or even give females an advantage, in certain communication situations.
Robust stabilization for a class of nonlinear large-scale systems with unmatched uncertainties

In this paper, asymptotic stabilization for a class of nonlinear large-scale systems with unmatched uncertainties is investigated. Two types of robust control algorithms are proposed to stabilize the uncertain nonlinear large-scale systems asymptotically provided that the nominal systems are asymptotically stable and the unmatched uncertainties are equivalently matched. The decentralized control utilizes the local state of each subsystems as the feedback information. The two-level control uses the local state as well as the states of the state of the connecting subsystems. An example is used to illustrate the proposed control method.
DNA ring closure mediated by protein HU.

Abstract The histone-like protein HU serves as an accessory factor that can facilitate the interaction of certain proteins with their specific DNA binding sites. Examples occur in different systems for prokaryotic DNA replication, transcription, and gene regulation. The protein-DNA interactions that are stimulated by HU generally involve coiling or looping of the DNA, and the possibility has been considered that HU exerts its effect by contributing flexibility to different DNA binding sites, but there has been no direct demonstration of this. To explore the possibility that HU can mediate tight DNA curvatures, we studied its effect on the formation of DNA circles when DNA ligase cyclizes short linear DNA fragments. It is demonstrated that HU greatly increases the cyclization rates of all fragments that were examined having lengths greater than 98 base pairs. Fragments of 99, 108, 120, or 126 base pairs could not cyclize in the absence of HU, but cyclization went rapidly with HU, showing that HU can mediate very tight DNA curvatures.
The Diffusion-Synthetic Acceleration of Transport Iterations, with Application to a Radiation Hydrodynamics Problem

Publisher Summary Radiation hydrodynamics treats the interactions of thermal radiation with matter. Thermal radiation is taken to mean electromagnetic radiation of atomic origin, obtained from the processes of scattering, absorption, and thermal emission. The radiation field is described by an equation of transfer, which is a Boltzmann transport equation for photons. From a computational viewpoint, time-dependent radiative transfer problems in emitting media are difficult to solve. In general, their solution involves an equation with seven independent variables for the radiation field, along with the additional equations describing the mass, momentum, and energy balance of the underlying medium. This chapter describes new numerical methods for solving such problems. It also discusses three aspects of the solution method: the time dependence, the intimate coupling between the radiation field and the medium, and the iteration acceleration of the equation of transfer. The time dependence is treated implicitly, that is, the equation of transfer is written in terms of the dependent variables evaluated at the advanced time.
Adapting an evidence-based HIV prevention intervention for pregnant African-American women in substance abuse treatment

An adaptation of an evidence-based, woman-focused intervention designed to reduce HIV risk behaviors was conducted for pregnant, African-American women in substance abuse treatment in North Carolina. The intervention adaptation process included focus groups, expert panels, and the filming of women who spoke about their experiences with pregnancy, drug use, sex risk behaviors, HIV testing and treatment, need for substance abuse treatment, violence, and victimization. The assessment instrument was adapted for pregnant women and the intervention was organized into a 4-session PowerPoint presentation, with an additional session if a woman tested positive for HIV. All sessions and assessment instrument were installed on laptop computers for portability in treatment programs. We pilot tested our adaptation with 59 pregnant African-American women who had used an illicit drug within the past year and were enrolled in substance abuse treatment. At baseline, 41% were currently homeless, 76% were unemployed, 90% had not planned their current pregnancy, and approximately 70% reported drug use since finding out about the pregnancy. This sample of participants rated the intervention sessions and were highly satisfied with their experience, resulting in a mean satisfaction score of 6.5 out of 7. Pregnant African-American women who use drugs need substance abuse treatment that they do not currently access. Woman-focused HIV interventions help to address intersecting risk behaviors and need for treatment prevalent among this vulnerable group.
Spin-orbit scattering in dx2-y2 superconductors

We show that spin-orbit scattering off an isolated magnetic impurity in a singlet dx2-y2 superconductor generates a dxy order parameter with locally broken time-reversal symmetry. A consequence of the induced dxy component are orbital charge currents and a magnetic field in the vicinity of the magnetic impurity.