cssi/SciSciGPT-SciSciNet huggingface dataset:
Canine Proliferative and Necrotizing Tracheobronchitis, with Intranuclear Inclusion-Body and Hyaline Membrane Formation

Diffuse proliferative and necrotizing trachcobronchitis, intranuclear inclusions, and pulmonary hyaline membranes were found in a 1-year-old female dachshund which was killed because of severe respiratory disease. Histologically the lesions resemble those described in adenoviral infections in calves, pigs, and man but a specific cause was not determined.
General bounds and inequalities in order statistics

This article is primarily a review of recent work on inequalities requiring no or only mild ssumptions.As feature,unified approaches are given for the derivation of algebraic inequalities involving linear functions of order statistics. Various inequalities for the expected value of such functions are presented. A new result is that a class of these inequalities can be improved by use of a theorem for ordered sums. Some other recent results are noted. Applications are indicated throughout.
Visuospatial attention in schizophrenia: deficits in broad monitoring.

Although selective attention is thought to be impaired in people with schizophrenia (PSZ), prior research has found no deficit in the ability to select 1 location and withdraw attention from another. PSZ and healthy control subjects (HCS) performed a stimulus detection task in which 1, 2, or all 4 peripheral target locations were cued. When 1 or 2 locations were cued, both PSZ and HCS responded faster when the target appeared at a cued than uncued location. However, increases in the number of validly cued locations had much more deleterious effects on performance for PSZ than HCS, especially for targets of low contrast whose detection was more dependent on attention. PSZ also responded more slowly in trials with 4 cued locations relative to trials with 1 or 2 invalidly cued locations. Thus, visuospatial attention deficits in schizophrenia arise when broad monitoring is required rather than when attention must be focused narrowly.
Unleashing Mobility in the Organization: A Time-Geography Perspective

The increased fluidity and agility of organizations demand the smooth mediation of information technology (IT) between user and task. As rigid hierarchies are giving way to open, loosely-coupled, mobile ways for collaborative business, mobility enabled by IT tools has been proposed as potential capability that can provide new dimensions in such mediation. But, few studies have provided an integrative theoretical framework on mobility. In addition, most studies have focused on either spatial or temporal dimensions of mobility, while ignoring the contextual dimension. In this paper, we propose a framework that is designed to capture the emergent impact of the use of mobile tools in the organization. It draws upon a time-geography perspective in building an integrated framework of three aspects of mobility constraints: capability, coupling, and regulatory. The usefulness of the framework is illustrated using a case study on the implementation of mobile devices in the Center City District (CCD) of Philadelphia. The paper concludes with contributions and recommendations for future research.
STRUCTURING AND INTERPRETING THE EXPERIENCE OF EARLY MODERN EUROPEANS

Archives of the scientific revolution: the formation and exchange of ideas in seventeenth-century Europe . Edited by Michael Hunter. Woodbridge: Boydell Press, 1998. Pp. xii + 216. ISBN 0–8511–553–7. £45.00. The peasantries of Europe from the fourteenth to the eighteenth centuries . Edited by Tom Scott. London: Longman, 1998. Pp. xi + 416. ISBN 0–582–10131-X. £19.99. Civil society and fanaticism: conjoined histories . By Dominique Colas. Translated by Amy Jacobs. Stanford: Stanford University Press, 1997. Pp. xxx + 480. ISBN 0–8047–2736–8. £14.95. The quest for compromise: peacemakers in Counter-Reformation Vienna . By Howard Louthan. Cambridge: Cambridge University Press, 1997. Pp. xvi + 185. ISBN 0–531–58082-X. £35.00. Each of the four volumes at hand examines a different yet vital aspect of European society between the late middle ages and the beginnings of industrialization. The field is far too diverse and the approaches too complex to expect a commonality among these works, excepting a shared temporal and geographic concentration. Still, the themes and subjects reveal some of the issues that have captured recent attention and show how scholars propose to go about exploring them. They suggest the interests of historians of early modern Europe, their distinctive perspectives, and varying methodologies. The collective reach extends from deciphering the papers and manuscripts left by participants in the scientific revolution to an exploration of the immense yet largely reticent peasant world, an attempt to establish the origins and trace the development of today's ongoing discussion over civil society and fanaticism, and finally a study of four peacemakers who urged religious moderation at the imperial court of Counter-Reformation Vienna. Put slightly differently, these studies raise fundamental questions about the sources upon which scholars depend, the nature and utility of historical models, and the relationship between contemporary concerns and our collective past, whether they be issues of civil society or irenic accommodation.
Beyond Phylotyping: Understanding the Impact of Gut Microbiota on Host Biology

Background Microbial constituents of the gut microbiome interact with each other and the host to alter the luminal environment and impact development, motility, and homeostasis of the gut. Powerful methods are becoming available to investigate connections between the gut microbiome and human health. While high-throughput sequencing of 16S rRNA genes can be used to identify and enumerate microbes in the gut, advances in several techniques (e.g., metagenomics, metatranscriptomics, metabolomics, and metaproteomics) are providing a clearer view as to the specific activities of the microbiota in the context of functional host–microbe interactions. Testing emergent hypotheses regarding microbial effects on host biology, which arise from analyses of ‘Big Data’ generated from massive parallel high-throughput sequencing technology and spectroscopic techniques, to guide translational research is an important goal for the future. Insights regarding the fundamental operating principles of the gut microbiota should lay the foundation for rational manipulation of the microbiota to promote human health. Purpose In this review, we provide an overview of current research on the gut microbiome emphasizing current state-of-the-art technologies, approaches, and directions for improvement of our understanding of the impact of the gut microbiota with specific focus on gastrointestinal motility disorders.
Meta-analysis of high-latitude nitrogen-addition and warming studies implies ecological mechanisms overlooked by land models

Abstract. Accurate representation of ecosystem processes in land models is crucial for reducing predictive uncertainty in energy and greenhouse gas feedbacks with the climate. Here we describe an observational and modeling meta-analysis approach to benchmark land models, and apply the method to the land model CLM4.5 with two versions of belowground biogeochemistry. We focused our analysis on the aboveground and belowground responses to warming and nitrogen addition in high-latitude ecosystems, and identified absent or poorly parameterized mechanisms in CLM4.5. While the two model versions predicted similar soil carbon stock trajectories following both warming and nitrogen addition, other predicted variables (e.g., belowground respiration) differed from observations in both magnitude and direction, indicating that CLM4.5 has inadequate underlying mechanisms for representing high-latitude ecosystems. On the basis of observational synthesis, we attribute the model–observation differences to missing representations of microbial dynamics, aboveground and belowground coupling, and nutrient cycling, and we use the observational meta-analysis to discuss potential approaches to improving the current models. However, we also urge caution concerning the selection of data sets and experiments for meta-analysis. For example, the concentrations of nitrogen applied in the synthesized field experiments (average = 72 kg ha−1 yr−1) are many times higher than projected soil nitrogen concentrations (from nitrogen deposition and release during mineralization), which precludes a rigorous evaluation of the model responses to likely nitrogen perturbations. Overall, we demonstrate that elucidating ecological mechanisms via meta-analysis can identify deficiencies in ecosystem models and empirical experiments.
Internalizing the Climate Externality: Can a Uniform Price Commitment Help?

It is difficult to resolve the global warming free-rider externality problem by negotiating many different quantity targets. By contrast, negotiating a single internationally-binding minimum carbon price (the proceeds from which are domestically retained) counters self-interest by incentivizing agents to internalize the externality. In this contribution I attempt to sketch out, mostly with verbal arguments, the sense in which each agent's extra cost from a higher emissions price is counter-balanced by that agent's extra benefit from inducing all other agents to simultaneously lower their emissions in response to the higher price. Some implications are discussed. While the paper could be centered on a more formal model, here the tone of the discussion resembles more that of an exploratory think piece directed to policy-makers and the general public.
The Indispensability of the Humanities for the 21st Century

This essay surveys the state of the humanities at this critical time. What will be the role of the humanities at the end of this century and beyond? I discuss the “crisis of the humanities” by examining the current challenges of globalization, economic shifts, and extensive budget cuts. I also discuss the social and political divisions that contribute to a crisis within the humanities. Since the culture wars that began in the 1960’s, the content, scope, and focus of the humanities have changed dramatically, and this has impacted how the humanities are perceived and valued by the general public. The second half of the essay makes the case for the vital importance of the humanities. I argue that the fate of the humanities is inseparable from the future of human beings. I highlight the current problems of war, environmental degradation, and mass surveillance that must be managed before they overwhelm and derail the potential for dramatic progress. Following recent scholarship and research trends, I explain how technological advancements will lead to the most significant evolutionary changes to the human being in aeons. Through technologies such as bionics, transgenesis, robotics, genetic engineering, and artificial intelligence, Homo sapiens might be enabled to transcend its former limits and usher in an era of transhumanism. The relevant question is: What do we want to be? I argue that enhancement technologies will make their beneficiaries more robotic and less human, and explain why we must treasure the advantages of our distinctly human capacities and resist the prospect of empowering ourselves to become automatons. My underlying thesis is that developing an understanding of the most insightful ideas and cultivating an appreciation for the greatest creative works that humankind has produced will be crucial for maintaining our humanity. The humanities thus make a unique and indispensable contribution to defining what and who we want our descendants to be.
U.S. Discovery and Foreign Blocking Statutes

What is the reality between U.S. discovery and the foreign blocking statutes that impede it in France and other civil law states? How should we understand their interface at a time when companies are multinational in composition as well as in their areas of commerce? U.S. courts grapple with the challenge of understanding why they should adhere to strictures that seem to compromise constitutional or quasi-constitutional rights of American plaintiffs, while French and German lawyers and judges struggle with the challenges U.S. discovery poses to values of privacy and fair trial procedure in their legal systems. This article seeks to address these issues.
Foraging Range and Distribution of Honey Bees Used for Carrot and Onion Pollination

A magnetic recapture system was used to determine the foraging range and distribution of bees from 389 hives in 29 apiaries (area about 12 km in diameter) to adjacent fields of carrots and onions grown for seed production. Bees from hives around the field perimeters showed intensive, localized foraging activity near their hives (mean flight distance = 266 m). Species diversity requirements were indicated when subpopulations bypassed profitable foraging areas and foraged on different crops at greater distances. Significant bee populations were attracted from distant apiaries, e.g., 3700 m. The mean flight distance to carrots (1663 m) indicated a greater attraction than for onions to bees from distant apiaries (557 m). The frequencies of pollen foragers were 7 and 66% for onions and carrots, respectively. Nectar sugar concentration was similar (ca 37%) for carrots and onions. Strategies are discussed for enhancing the isolation of nearby fields when interfield pollination is undesirable. Concepts are discussed concerning (a) differential flight range for pollen vs. nectar collectors, and (b) determination of relative plant attraction to honey bees.
Group bias in cooperative norm enforcement

A hallmark of human social cognition is the tendency for both adults and children to favour members of their own groups. Critically, this in-group bias exerts a strong influence on cooperative decision-making: people (i) tend to share more with members of their in-group and (ii) differentially enforce fairness norms depending on the group membership of their interaction partners. But why do people show these group biases in cooperation? One possibility is that the enforcement of cooperative norm violations is an evolved mechanism supporting within-group cooperation (Norms-Focused Hypothesis). Alternatively, group bias in cooperation could be a by-product of more general affective preferences for in-group members (Mere Preferences Hypothesis). Here, we appraise evidence from studies of both adults and children with the goal of understanding whether one of these two accounts is better supported by existing data. While the pattern of evidence is complex, much of it is broadly consistent with the Mere Preferences Hypothesis and little is uniquely supportive of the Norms-Focused Hypothesis. We highlight possible reasons for this complexity and suggest ways that future work can continue to help us understand the important relationship between group bias and cooperation.
What Marketing Strategy Matters? Examining a Contingency Model of the Relationship Between Marketing Performance Management and Business Unit Performance

A firm’s ability to understand the effects of its marketing resource deployments continues to be a major focus of organizations. In order to assess the effectiveness and efficiency of marketing implementation, the ability to measure and track activities is vital. Marketing performance measurement systems provide the marketing function with the capability to measure the impact across a variety of marketing activities and to evaluate the performance of marketing activities vis a vis an ample set of metrics (O’Sullivan & Abela, 2007).
Models of the mind: their role in the clinical teaching of psychoanalytic psychotherapy.

Psychotherapy trainees often hold implicit models of pathogenesis and cure, which can distort their understanding of a supervisor’s suggestions. We identify two such models, the “passive-learning” ...
Acute aortic dissection. Twelve-year medical and surgical experience.

The various methods of treatment are evaluated, with emphasis on comparison of medical and surgical management. The distinction between ascending and descending arch dissections is stressed.
Estimation of the bus admittance matrix for transmission systems from synchrophasor data

This research proposes a technique for determining the bus admittance matrix Ybus for large-scale power systems from recorded synchrophasor measurements. The approach is based on recognizing that measurements of bus injection currents Ibus can be viewed as signals produced by a random process. In this manner, the corresponding bus voltages Vbus are also stochastic signals that are related through a cross-covariance matrix to the injection current vector Ibus. Using estimation techniques developed for statistical signal processing, the cross-covariance matrix is shown to be Ybus. The increasing use of synchrophasors has enabled large-scale data collection of time synchronized bus injection currents and voltages. The new Zbus estimation method is applied to the IEEE 68 bus benchmark system to demonstrate the validity of approach. The accuracy and convergence rate of the method is evaluated under conditions corresponding to wide-area synchrophasors data collection. The results indicate that the method is broadly applicable to determining Ybus and Zbus for electric power transmission and distribution systems equipped with synchrophasor data collection technology.
Defending Mathematical Apriorism

The claim that mathematics is synthetic a priori is most commonly and most famously attacked by the logicists. Logicists usually argue against the syntheticity of mathematics in order to argue against Kant’s thesis that mathematics possesses an extra-logical subject matter. Frege, Russell, and others endeavoured to show that Kant was wrong about the content of mathematics by showing how all true mathematical statements can be derived, once certain primitives (e.g., for Frege, for arithmetic, ‘ number’, ‘immediate predecessor’, ‘0’, and the ‘ancestral’ relation) have been defined in logical terminology alone.1 This is generally taken as an attempt to show that mathematics is analytic a priori. (This label is not accurate for Russell’s logicism, as he believed even logic to be synthetic. However, the following general point still stands.) If successful, logicism would have shown mathematics to be independent of ‘intuitions’ or extra-definitional content, for its foundation would essentially be that of logic. Logicism and the related foundational programme of set theory are addressed below, in the following chapters.
14 days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults

We examined the effect of 14 days of bed rest on skeletal muscle satellite cell content and fiber type atrophy and in middle-aged adults. Bed rest, a ground-based space flight analog, induces robus...
The Asymptotic Profiles In Forced Convection Turbulent Boundary Layers

Two new inner and outer temperature scalings are derived by means of similarity analysis of the equations of motion in forced convection turbulent boundary layers. Using the new scalings, the temperature profiles collapse into a single curve regardless of the strength of pressure gradient (PG) and changes in upstream conditions. Thus, the true asymptotic solution exists for temperature field even at a finite Peclet number.
The Human Virome: Implications for Clinical Practice in Transplantation Medicine

Advances in DNA sequencing technology have provided an unprecedented opportunity to study the human virome. Transplant recipients and other immunocompromised hosts are at particular risk for developing virus-related pathology; thus, the impact of the virome on health and disease may be even more relevant in this population. Here, we discuss technical considerations in studying the human virome, the current literature on the virome in transplant recipients, and near-future applications of sequence-based findings that can further our understanding of viruses in transplantation medicine.
First-Year College Students Increase Food Label–Reading Behaviors and Improve Food Choices in a Personal Nutrition Seminar Course

ABSTRACTBackground: Poor dietary behaviors are risk factors for developing chronic diseases that plague public health. Purpose: This study sought to determine the differences in pre and post food label and food choice scores among first-year college students at the beginning and end of the semester. Case analyses were conducted to evaluate individualized changes. Methods: Students completed pre and post electronic surveys. Food label and food choice scores were computed. Reliability analysis was conducted for each computed score. Paired t tests were employed to compare the differences in scores at pre and post measure. Case analyses showed differences per individual student. Results: Paired t test revealed a statistically significant difference with an increase in food label–reading behavior (P = .000) and food choice behavior (P = .000). Case analyses showed that 27% of students practiced food label reading more frequently in at least one category above at post measure and 29% indicated choosing healthie...
Die ionisierenden Potentialwellen beim Funkendurchschlag

Extending earlier studies on spark breakdown, the development of the impulse prebreakdown streamers leading to complete breakdown were investigated. By taking advantage of the proportionality between point potential and length of the positive Lichtenberg figure produced, the potential of the streamer tips progressing from a point anode towards a plane cathode were determined. It was found that the streamer tip potential decreases as streamer advances. At voltages much lower than sparking potential this decrease is rapid. By approaching the sparking potential the loss of tip potential diminishes considerably near the anode. The decrease of potential remains very rapid near the cathode until sparking potential is reached. At the cathode the tip potential increases with the applied potential. At a certain value electrons are emitted from the cathode under the influence of high tip fields. These electrons are accelerated towards the tips forming avalanches by collision. These avalanches appear on the photographic film as minute dots whose number and density depend on the intensity of tip fields. If the applied potential exceeds the sparking voltage, tip potentials are recorded on the cathode between 15 and 25 kV. The avalanches formed in the high intensity field region reach the critical size and form negative, anode — directed streamers. These streamers appear on the film as negative Lichtenberg figures. This ionising potential wave, known as return stroke, travels along the channel of the positive primary streamer. It increases its ionisation to such a degree that the main stroke can take place.
Postoperative Refractive Errors Following Pediatric Cataract Extraction with Intraocular Lens Implantation

Purpose: Advances in surgical techniques allow implantation of intraocular lenses (IOL) with cataract extraction, even in young children. However, there are several challenges unique to the pediatr...
Brief Announcement: Coloring-based Task Mapping for Dragonfly Systems

Task mapping is the assignment of job tasks to nodes. Traditionally, the goal of task mapping is to maximize locality, reducing the number of network hops needed to deliver messages as a way of reducing bandwidth consumption. We show that on a Dragonfly topology, such a strategy can be counterproductive because, while traffic is reduced, it is also concentrated on only a few global links, creating hot spots. We formulate the balanced adjacency coloring problem to design mappings that evenly spread network traffic, give optimal algorithms to solve it for a number of cases, and use simulations to show that mappings based on these algorithms can reduce the communication time of a stencil job by up to 20%.
Identifying barriers to cancer survivors sharing their survivorship care plans with their healthcare provider

To understand what factors influence whether a cancer survivor will share their survivorship care plan (SCP) with their healthcare provider (HCP). We used data from 3231 cancer survivors who utilized the OncoLink SCP resource between 2009 and 2016. Random forest and stepwise regression were used to identify predictors of SCP satisfaction and barriers to survivors sharing their care plans with their HCPs. Eighty-seven percent of users rated their satisfaction with their SCP as good or better; however, only 70% of survivors planned to share their SCP with their HCP. The most commonly reported reason for not sharing was a feeling that their HCP would not care. Self-reported satisfaction with their SCP was strongest predictor of whether a survivor would share their SCP. Gender, cancer status, number of chemotherapies received, and who was managing their healthcare were all associated with self-reported survivor satisfaction with their SCP. Survivor satisfaction with SCPs was high, but there was a disconnect in the number of satisfied survivors and the number of survivors planning to share their SCP with their HCP. To bridge this gap, additional prompts that HCPs are expecting this information should be added to the care plans. One of the primary functions of survivorship care plans is to improve communication between survivor and healthcare provider. While survivors are overwhelmingly satisfied with their SCP, additional steps are necessary to get survivors to share their SCP with their HCP.
Ionophore Use and Toxicosis in Cattle

Ionophores comprise a rapidly expanding class of antibiotics produced by filamentous branching bacteria of the order Actinomycetales. The use of ionophores as coccidiostats and growth promotants has resulted in the occurrence of toxicoses in target and nontarget species. Clinical and pathologic effects of ionophore poisoning are caused by bioactivity and damage to excitable tissues such as cardiac muscle, skeletal muscle, smooth muscle, and the nervous system. Ionophore toxicoses are often related to errors in feed mixing, so the practitioner should give primary importance to the removal of suspect feeds and testing to confirm excessive exposure.
Zinc nutritional status modifies renal osteodystrophy in uremic rats

Background Previous studies from our laboratories suggested that zinc depletion reduces the circulating level of 1,25-dihydroxycholecalciferol (1,25(OH)2D, calcitriol) in calcium- and phosphorus-depleted rats with normal renal function, and rats with uremia. Since calcitriol synthesis is in part dependent on renal function, we studied levels of circulating vitamin D metabolites, PTH response, mineral balance and bone histomorphometry in animals with different zinc nutritional and renal functional status. Methods Fifty-eight male Sprague-Dawley rats were pair-fed zinc-replete (+) or -deplete (-) diets for two weeks. Thereafter, half of each paired group underwent nephrectomy (N), while half had sham (S) operations. Animals were observed for eight weeks after surgery. External mineral balances of zinc, calcium, phosphate and magnesium were determined before surgery, and 1, 2 and 7 weeks after surgery. Plasma creatinine, zinc, calcium, phosphorus, magnesium, 25-hydroxycholecalciferol, calcitriol and PTH were determined at sacrifice. Static and dynamic bone histomorphometry was determined by standard techniques. Results After an 8-week observation period, zinc-depleted animals had lower plasma zinc levels, and nephrectomized animals had lower creatinine clearances than respective controls at sacrifice. Plasma calcium and phosphorus concentrations were similar in all four groups at sacrifice. Plasma magnesium concentrations were similar in groups with renal insufficiency, regardless of zinc nutritional status. Plasma 25-hydroxycholecalciferol and calcitriol levels were similar in all groups. There was no difference between mean PTH concentration in sham-operated animals, regardless of zinc nutritional status. Although nephrectomized groups' PTH levels were increased compared to S controls, PTH levels were increased in +Zn/N animals compared to the -Zn/N group. Zinc-deplete groups had consistent negative net zinc balance, however, there was no consistent effect of nephrectomy on external calcium, phosphorus, or magnesium balance, when nephrectomized groups of different zinc nutritional status were compared. Nephrectomized animals had histomorphometric changes indicative of higher bone turnover and abnormal mineralization. Zinc deficiency was associated with less evidence of increased parathyroid hormone activity on bone in nephrectomized rats. Conclusions Zinc depletion limits the increase in plasma PTH concentration and the expression of secondary hyperparathyroid bone disease during the development of renal insufficiency in the renal ablation model of uremia in rats. The mechanism underlying this effect is unknown, but may involve a direct effect of zinc on the synthesis, release, metabolic clearance, and/or action of PTH on the cellular level, on the interrelationship of calcitriol and PTH, or a direct effect of zinc on bone mineral metabolism. These data highlight the potential relevance of zinc nutritional status to mineral metabolism in patients with chronic renal insufficiency and end-stage renal disease.
Functional Psychological Assessment and Clinical Judgment

An important goal of psychological assessment is to increase the validity of clinical judgments. Judgments about a client’s behavior problems, factors that contribute to those problems, and the best strategies of intervention with a client should be more valid when based on accurate information from psychological assessment.
Single optical fiber photoacoustic sensing probe

In this paper, a novel photoacoustic (PA) sensing probe design consisting of single optical fiber is reported. The same optical fiber is used for light delivery, which also serves as an acoustic delay line to relay the PA signal. As the key feature of the design, the ultrasound transducer is made optically-transparent to allow excitation light to pass through. This probe design provides three major benefits, including miniaturization, co-registered optical excitation and acoustic detection, and clear separation of PA signal from interference signals. Testing results show that PA probe provides good sensitivity and high linearity.
Comorbidity of age-related macular degeneration with Alzheimer’s disease: A histopathologic case-control study

Introduction Previous studies evaluating the association between clinically diagnosed Alzheimer's disease (AD) and age-related macular degeneration (AMD) have generated conflicting results. This study is the first to assess whether AMD prevalence is higher in AD patients than non-AD controls by using histopathology to definitively diagnose AD. Methods This was a retrospective case-control study utilizing diagnostic information extracted from autopsy reports of patients age 75 and above, including 115 with a neuropathological diagnosis of AD and 57 age-matched normal controls. Results The rate of AMD was not significantly higher in AD cases (53.0%) than in controls (59.6%) (z = 0.820, p = 0.794). AMD severity as determined by Sarks score was similar between AD patients and controls (χ2 = 2.96, p = 0.706). There was also no significant association between Braak stage of AD severity and AMD (χ2 = 4.55, p = 0.602). Discussion No significant effect of AD diagnosis or pathologic severity on AMD comorbidity was found, suggesting that any shared mechanisms between AMD and AD may be nondeterministic.
Peroxisome proliferator‐activated receptor gamma controls prostate cancer cell growth through AR‐dependent and independent mechanisms

Background Prostate cancer (PC) remains a leading cause of cancer mortality and the most successful chemopreventative and treatment strategies for PC come from targeting the androgen receptor (AR). Although AR plays a key role, it is likely that other molecular pathways also contribute to PC, making it essential to identify and develop drugs against novel targets. Recent studies have identified peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that regulates fatty acid (FA) metabolism, as a novel target in PC, and suggest that inhibitors of PPARγ could be used to treat existing disease. We hypothesized that PPARγ acts through AR-dependent and independent mechanisms to control PC development and growth and that PPARγ inhibition is a viable PC treatment strategy. Methods Immunohistochemistry was used to determine expression of PPARү in a cohort of patients with PC. Standard molecular techniques were used to investigate the PPARү signaling in PC cells as well a xenograft mouse model to test PPARү inhibition in vivo. Kaplan-Meier curves were created using cBioportal. Results We confirmed the expression of PPARү in human PC. We then showed that small molecule inhibition of PPARγ decreases the growth of AR-positive and -negative PC cells in vitro and that T0070907, a potent PPARγ antagonist, significantly decreased the growth of human PC xenografts in nude mice. We found that PPARγ antagonists or small interfering RNA (siRNA) do not affect mitochondrial activity nor do they cause apoptosis; instead, they arrest the cell cycle. In AR-positive PC cells, antagonists and siRNAs reduce AR transcript and protein levels, which could contribute to growth inhibition. AR-independent effects on growth appear to be mediated by effects on FA metabolism as the specific FASN inhibitor, Fasnall, inhibited PC cell growth but did not have an additive effect when combined with PPARγ antagonists. Patients with increased PPARү target gene expression, but not alterations in PPARү itself, were found to have significantly worse overall survival. Conclusions Having elucidated the direct cancer cell effects of PPARγ inhibition, our studies have helped to determine the role of PPARγ in PC growth, and support the hypothesis that PPARγ inhibition is an effective strategy for PC treatment.
Evaluating the Sensitivity of Projected Reservoir Reliability to the Choice of Climate Projection: A Case Study of Bull Run Watershed, Portland, Oregon

Climate change has the potential to alter the quantity and timing of runoff, which may pose significant challenges for reservoir management. One challenge is developing operating policies for an unknown and uncertain future. Here, we develop a suite of ‘optimal’ operating policies for the reservoir system of Portland, Oregon. We assess the sensitivity of projected reservoir reliability to the choice of GCMs and time periods used to develop each of our policies. Results indicate that, while different GCMs and fitting periods produce different optimal operating policies, when those policies are applied across all the other GCM scenarios, the overall projected reliability does not change due to the great variability between simulations. Across the simulations, we note a trend of decreasing reliability in the future which is not sensitive to the choice of GCM or fitting period. This indicates that the projected reliability is dominated by uncertainty in climate projections that cannot be mitigated by tuning operating policies to projected changes.
Technical Note—Time Inconsistency of Optimal Policies of Distributionally Robust Inventory Models

The authors extend previous studies of time inconsistency to risk averse (distributionally robust) inventory models and show that time inconsistency is not unique to robust multistage decision maki...
Normalisr: normalization and association testing for single-cell CRISPR screen and co-expression

Abstract Single-cell RNA sequencing (scRNA-seq) provides unprecedented technical and statistical potential to study gene regulation but is subject to technical variations and sparsity. Here we present Normalisr, a linear-model-based normalization and statistical hypothesis testing framework that unifies single-cell differential expression, co-expression, and CRISPR scRNA-seq screen analyses. By systematically detecting and removing nonlinear confounding from library size, Normalisr achieves high sensitivity, specificity, speed, and generalizability across multiple scRNA-seq protocols and experimental conditions with unbiased P-value estimation. We use Normalisr to reconstruct robust gene regulatory networks from trans-effects of gRNAs in large-scale CRISPRi scRNA-seq screens and gene-level co-expression networks from conventional scRNA-seq.
Enhancing social interactions for youth with autism spectrum disorder through training programs for typically developing peers: A systematic review

Abstract Background Individuals diagnosed with autism spectrum disorder (ASD) characteristically demonstrate deficits in social communication, making it challenging for children and adolescents with ASD to form and maintain friendships. Widely implemented social skills interventions aim to ameliorate these deficits through explicit instruction. Despite reported gains in social competency, many children with ASD may not successfully generalize learned social skills to interactions outside the interventions. One barrier to generalization may be stigma from typically developing (TD) peers. Specifically, TD peers who could serve as social partners for individuals with ASD often perceive the social behavior of children with ASD as atypical and demonstrate negative attitudes toward and a preference for social distance from these individuals. Method This systematic review aimed to identify the techniques employed by, and the impact of, TD peer intervention programs providing TD school-age children and adolescents with information about ASD and those training peers to be peer social models on peer perceptions of ASD. This search was conducted using three databases (i.e., PsychINFO, PubMed, Web of Science) and found 14 articles meeting inclusion criteria. Results Results demonstrate that peer training programs employ multiple methods including didactic trainings, group discussions, activities, opportunities for video or in-person exposure to individuals with ASD, and opportunities to implement learned strategies with peers to disseminate varying levels and types of information (e.g., descriptive, explanatory, directive) about ASD to participants. Conclusions Overall, results of such TD peer training programs demonstrate significant reductions in peer stigma and improvements in peer mediating abilities post-intervention.
Parent–child attachment security is associated with preschoolers’ memory accuracy for emotional life events through sensitive parental reminiscing

Abstract There is considerable controversy regarding the accuracy and suggestibility of children’s autobiographical memory for emotionally salient life events. Attachment perspectives of autobiographical memory development identify the attachment security of parent–child dyads and parents’ emotional support and coherence during reminiscing with their children as critical mechanisms underlying children’s memory accuracy and suggestibility. In the current investigation, 72 preschool-aged children (M = 4.01 years, SD = 0.85; 44 female) reminisced with their parents about times they felt happy, sad, scared, and angry. Children were then independently interviewed about these experiences by an unfamiliar researcher using free recall, specific questions (i.e., questions about factual details), and misleading questions (i.e., questions suggesting false details). Parents completed an assessment of their children’s attachment security within the parent–child relationship. Results revealed significant indirect effects of parent–child attachment security on children’s memory accuracy through parental sensitive guidance during reminiscing when cognitive (i.e., intelligence) and behavioral (i.e., temperament, behavior problems) covariates were statistically controlled. Parent–child attachment security was positively associated with parental sensitive guidance during reminiscing, which, in turn, was positively associated with the accuracy of children’s independent reports. The findings support attachment perspectives of autobiographical memory by identifying emotionally sensitive and coherent reminiscing as a parenting behavior that explains in part associations between parent–child attachment security and children’s independent memory accuracy for emotional life events.
Market Fragility and Interconnectedness in the Asset Management Industry

The relationship between asset management activities and financial stability risks has been a frequent topic of discussion among financial market participants and regulators in recent years. This discussion has arisen in light of the significant growth in the asset management industry and the increased focus on financial stability risks in the aftermath of the financial crisis. My remarks are intended to highlight the underlying economics of these issues to help provide a better understanding of their nature and significance. They are informed by a continuously emerging body of academic research, some of which is being performed by staff at the SEC, and all of which demonstrates the inherent complexities in thinking about potential contributions of asset management practices to market fragility concerns.
Survival in cystic fibrosis after acute respiratory failure supported by extracorporeal membrane oxygenation and/or invasive mechanical ventilation

Abstract Background Despite therapeutic advances, people with cystic fibrosis (CF) develop progressive worsening and exacerbations of their lung disease, which can lead to acute respiratory failure. Historically, survival after mechanical ventilation (MV) has been poor. Outcomes related to use of extracorporeal membrane oxygenation (ECMO) have not been well described in CF. Methods We conducted a retrospective analysis of adult patients with CF admitted to the ICU for acute respiratory failure and requiring invasive MV with or without ECMO between July 1, 2006 and June 30, 2016. Separate analysis for the subgroup of MV patients who were eligible for transplant was conducted. Results Mortality for all patients with respiratory failure requiring advanced support was 37%. Ten of 28 (36%) MV patients, 10 of 26 (38%) ECMO+MV patients and 7 of the 21 (33%) transplant eligible MV patients died. Intensive care unit (ICU) length of stay (LOS) was 24.5±16.6 days for ECMO+MV; 12.9±9.0 days for MV (p=0.001), and 12.3 ±10 days for transplant eligible MV patients (p=0.005 for ECMO+MV comparison). Seven transplant eligible MV patients (33%) and 16 ECMO+MV patients (62%) underwent lung transplantation (p Conclusion Survival for CF patients with acute respiratory failure requiring MV with or without ECMO has improved over time. ECMO may be an appropriate modality for respiratory support in patients with CF and acute respiratory failure who have greater risk of death from MV alone.
Impact of COVID-19 on Latinos: A Social Determinants of Health Model and Scoping Review of the Literature

The purpose of this scoping review of the literature was to analyze the impact of the COVID-19 pandemic on the living conditions of Latinos (Hispanics) in the U.S. from a social determinants of hea...
Anticipatory Coping Diversity: Implications for Emotional, Physical, and Cognitive Reactivity to Daily Stressors.

OBJECTIVES This study examines the concept of anticipatory coping diversity, reflected in the evenness and richness of anticipatory coping strategies. The overarching goal of the present study is to show how individual differences in anticipatory coping diversity are associated with emotional, physical, and cognitive reactivity to daily stressors, and to examine whether these dynamic characteristics might differ between younger and older adults. METHOD 107 younger (M age = 19.44, range 18-36) and 116 older (M age = 64.71, range 60-90) participants reported on 1627 total days via an online daily diary study. Participants reported baseline demographic information (Day 1) and anticipatory coping, stressor exposure, negative affect, physical symptoms, and memory failures (Days 2-9). Anticipatory coping diversity was indexed at the person level using Shannon's entropy to capture the evenness and richness of anticipatory coping strategies across stressors. RESULTS People with more anticipatory coping diversity were less emotionally reactive, but more physically and cognitively reactive to daily stressors. Older adults exhibited less anticipatory coping diversity than younger adults, but the patterns of anticipatory coping diversity differences in reactivity appeared to be consistent across younger and older adults. DISCUSSION Anticipatory coping diversity reflects a useful index within the stress process that is associated with benefits as well as costs. These findings bridge dispositional and contextual approaches to coping and highlight the importance of understanding how deployment of coping strategies are related to well-being across the adult lifespan.
Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019.

Rationale: There is controversy concerning the association of chronic obstructive pulmonary disease (COPD) as an independent risk factor for mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19). We hypothesize that patients with COPD hospitalized for COVID-19 have increased mortality risk. Objective: To assess whether COPD increased the risk of mortality among patients hospitalized for COVID-19. Methods: We conducted a retrospective cohort analysis of patients with COVID-19 between February 10, 2020, and November 10, 2020, and hospitalized within 14 days of diagnosis. Electronic health records from U.S. facilities (Optum COVID-19 data) were used. Results: In our cohort of 31,526 patients, 3030 (9.6%) died during hospitalization. Mortality in patients with COPD was higher than that of patients without COPD, 14.02% and 8.8%, respectively. Univariate (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.54 to 1.84) and multivariate (OR 1.33; 95% CI 1.18 to 1.50) analysis showed that patients with COPD had greater odds of death due to COVID-19 than patients without COPD. We found significant interactions between COPD and sex and COPD and age. Specifically, the increased mortality risk associated with COPD was observed among female (OR 1.62; 95% CI 1.36 to 1.95) but not male patients (OR 1.14; 95% CI 0.97 to 1.34); and in patients aged 40 to 64 (OR 1.42; 95% CI 1.07 to 1.90) and 65 to 79 (OR 1.48; 95% CI 1.23 to 1.78) years. Conclusions: COPD is an independent risk factor for death in adults aged 40 to 79 years hospitalized with COVID-19 infection.