cssi/SciSciGPT-SciSciNet huggingface dataset:
Physiology of Hypothermic Circulatory Arrest and Retrograde Cerebral Perfusion

The fact that hypothermic circulatory arrest (HCA) may result in suboptimal cerebral protection during cardio-aortic surgery, especially if HCA is prolonged, has recently been increasingly acknowledged. We have explored the physiology of hypothermia to find ways to enhance its effectiveness, including use of retrograde cerebral perfusion (RCP). RCP has additional appeal for its potential utility in reducing embolic cerebral injury. We have carried out a series of investigations of hypothermic RCP in a chronic porcine model, monitoring metabolic, electrophysiological and behavioral recovery as well as histopathology.
Challenges of Medicine Across the Cultural Divide

Three incidents concerning caregivers and patients from different cultural groups illustrate medical challenges. A brief history of medicine in Africa during the colonial era illuminates some of the difficulties. I introduce the concept of medical pluralism and related ways of thinking as a synergistic solution. Finally I offer an approach to an integrative medical encounter.
Phase separation in Li x FePO 4 induced by correlation effects

We report on a significant failure of the local density approximation (LDA) and the generalized gradient approximation (GGA) to reproduce the phase stability and thermodynamics of mixed-valence ${\mathrm{Li}}_{x}{\mathrm{FePO}}_{4}$ compounds. Experimentally, ${\mathrm{Li}}_{x}{\mathrm{FePO}}_{4}$ compositions $(0l~xl~1)$ are known to be unstable and phase separate into ${\mathrm{LiFePO}}_{4}$ and ${\mathrm{FePO}}_{4}.$ However, first-principles calculations with LDA/GGA yield energetically favorable intermediate compounds and hence no phase separation. This qualitative failure of LDA/GGA seems to have its origin in the LDA/GGA self-interaction which delocalizes charge over the mixed-valence Fe ions, and is corrected by explicitly considering correlation effects in this material. This is demonstrated with LDA+U calculations which correctly predict phase separation in ${\mathrm{Li}}_{x}{\mathrm{FePO}}_{4}$ for $U\ensuremath{-}J\ensuremath{\gtrsim}3.5\mathrm{eV}.$ The origin of the destabilization of intermediate compounds is identified as electron localization and charge ordering at different iron sites. Introduction of correlation also yields more accurate electrochemical reaction energies between ${\mathrm{FePO}}_{4}/{\mathrm{Li}}_{x}{\mathrm{FePO}}_{4}$ and $\mathrm{Li}/{\mathrm{Li}}^{+}$ electrodes.
Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event.

Signal transducer and activator of transcription 5b (STAT5b) is a growth hormone (GH)-activated transcription factor and a master regulator of sexually dimorphic gene expression in the liver. Disruption of the GH hypothalamo-pituitary-liver axis controlling STAT5b activation can lead to metabolic dysregulation, steatosis, and liver cancer. Computational approaches were developed to identify factors that disrupt STAT5b function in a mouse liver gene expression compendium. A biomarker comprised of 144 STAT5b-dependent genes was derived using comparisons between wild-type male and wild-type female mice and between STAT5b-null and wild-type mice. Correlations between the STAT5b biomarker gene set and a test set comprised of expression datasets (biosets) with known effects on STAT5b function were evaluated using a rank-based test (the Running Fisher algorithm). Using a similarity p-value ≤ 10−4, the test achieved a balanced accuracy of 99% and 97% for detection of STAT5b activation or STAT5b suppression, respectively. The STAT5b biomarker gene set was then used to identify factors that activate (masculinize) or suppress (feminize) STAT5b function in an annotated mouse liver and primary hepatocyte gene expression compendium of ~1,850 datasets. Disruption of GH-regulated STAT5b is a common phenomenon in liver in vivo, with 5% and 29% of the male datasets, and 11% and 13% of the female datasets, associated with masculinization or feminization, respectively. As expected, liver STAT5b activation/masculinization occurred at puberty and suppression/feminization occurred during aging and in mutant mice with defects in GH signaling. A total of 70 genes were identified that have effects on STAT5b activation in genetic models in which the gene was inactivated or overexpressed. Other factors that affected liver STAT5b function were shown to include fasting, caloric restriction and infections. Together, these findings identify diverse factors that perturb the hypothalamo-pituitary-liver GH axis and disrupt GH-dependent STAT5b activation in mouse liver.
The interplay between genetic background and sexual dimorphism of doxorubicin-induced cardiotoxicity

Doxorubicin (DOX) is a very effective anticancer medication that is commonly used to treat hematological malignancies and solid tumors. Nevertheless, DOX is known to have cardiotoxic effects that may lead to cardiac dysfunction and failure. In experimental studies, female animals have been shown to be protected against DOX-induced cardiotoxicity; however, the evidence of this sexual dimorphism is inconclusive in clinical studies. Therefore, we sought to investigate whether genetic background could influence the sexual dimorphism of DOX-induced cardiotoxicity. Male and female Wistar Kyoto (WKY) and Spontaneous Hypertensive Heart Failure (SHHF) rats were used. DOX was administered in eight doses of 2 mg/kg/week and the rats were followed for an additional 12 weeks. Cardiac function was assessed by trans-thoracic echocardiography, systolic blood pressure was measured by the tail cuff method, and heart and kidney tissues were collected for histopathology. Female sex protected against DOX-induced weight loss and increase in blood pressure in the WKY rats, whereas it protected against DOX-induced cardiac dysfunction and the elevation of cardiac troponin in SHHF rats. In both strains, female sex was protective against DOX-induced nephrotoxicity. There was a strong correlation between DOX-induced renal pathology and DOX-induced cardiac dysfunction. This study highlights the importance of studying the interaction between sex and genetic background to determine the risk of DOX-induced cardiotoxicity. In addition, our findings suggest that DOX-induced nephrotoxicity may play a role in DOX-induced cardiac dysfunction in rodent models.
Imaginary Worlds: Modeled claims for cost-effectiveness published in PharmacoEconomics January 2015 to December 2015

The purpose of this review is to assess whether or not economic evaluation studies published in PharmacoEconomics in 2015 meet the standards of normal science. Two questions are key to the assessment: (i) did the authors attempt to generate testable claims as to the impact of the pharmaceutical product in health care systems and (ii) did the authors suggest how the claims might be evaluated? A total of 31 studies were evaluated, including 14 research articles, 8 systematic reviews and 9 reviews. Although the majority of the studies met recommended standards for cost-effectiveness analysis, none met the standards of normal science. They were best categorized as imaginary worlds or thought experiments. The reader has no idea whether the claims for the products are right or even if they were wrong. Journal editors have two options: (i) require authors to submit cost-effectiveness claims that are evaluable with a protocol suggesting how the claim may be evaluated or (ii) continue to publish non-evaluable cost-effectiveness claims but insist authors indicate that the claims are non-evaluable. Conflict of Interest None Type: Commentary
Monte carlo simulation of homogeneous binary nucleation: Toward a theory of sulfuric acid — water system

Publisher Summary This chapter provides a molecular level picture of the process, thereby motivating the development of a molecular theory that renders the quantitative prediction of 0the nucleation rate feasible. To begin to formulate a molecular theory of binary nucleation of sulfuric acid water, this chapter carries out Monte Carlo simulation on the model binary system of dipolar molecules and ion pairs. It evaluates the reversible work of cluster formation and the cluster size distribution for this system. As a first step toward a molecular theory of binary nucleation of sulfuric acid–water, a Monte Carlo simulation on the model binary system composed of spherical dipolar particles (i.e. H20) and ion pairs is performed. Despite its simplified nature, the model captures important molecular characteristics of acid–water interaction, such as dissociation of sulfuric acid in aqueous solution and the formation of hydrated acid molecules.
9 STUDIES OF MUTANT HUMAN ADENYLOSUCCINATE LYASE

Residual adenylosuccinate lyase activity was studied in cultured lymphoblasts from a pair of siblings who have mental retardation and autism, and who have been previously shown to exhibit a deficiency of the enzyme. Utilization of formate by intact cells showed de novo synthesis in the mutant lymphoblasts to be similar to normal, consistent with a partial deficiency of this enzyme as previously reported. The steady-state kinetics and thermal stability of adenylosuccinate lyase were examined in the lymphoblast lysates. The pH-activity curves were nearly identical for the mutant and normal cells, with an optimum in the region of pH 7.8. While the substrate affinity was not distinguishable from normal, there was a significant difference (p < 0.05) In the Vmax of the mutant cells. The lyase from normal cells exhibited an apparent Km of 3.3 ± 0.8 μM and a Vmax of 13.8 ± 0.9 nmol·mg−1·min−1. In the mutant cells, the lyase had an apparent Km of 2.6 ± 0.5 μM and Vmax of 6.7 ± 1.1 nmol mg−1·min−1. There was a significant difference between the normal and mutant cell lyases with regard to thermal stability. At 37°C, the half-time for inactivation was 22.2 hours for the normal cells and 15.7 hours for the mutant cell lysates, and at 60°C the half-times were 5.0 and 0.49 minutes for normal and mutant cell lysates, respectively. There was no evidence of inhibitory activity in the lysates of the mutant cells. The results are consistent with a structural mutation in the adenylosuccinate lyase gene of the affected individuals.
InTouch Wearables: Exploring Ambient Remote Touch in Child-Parent Relationships

InTouch Wearables is a set of wearables that consist of dresses and shoulder pieces that allow mother and child share remote touches through garments with ambient feedback. This was developed to explore how remote touches can convey emotion and help people stay connected between remote locations. This project was created based on the lead artist's personal experience with her child. In InTouch Wearables, a parent can increase the vividness of her conversation with a child through contextualized touch, and the loved ones may enhance the affective tone of their communication using a remote touch technology. All the electronic components of the garment for sensing human touches and actuating color-changing garment are integrated on the main fabrics. Audience will be able to touch and activate interaction between garments.
Challenges for electronic data interchange in becoming a global competitive tool

Lately, managers have been waving the flag about electronic data interchange (EDI) as a 'strategic weapon' in global competition. It is an innovative tool useful for accurate and timely interchange of business information. The major focus of EDI is 'business' related, not technology related. In this paper, these 'business' related issues, their complexity and challenges for harmonisation in the global business context are discussed.
Formative Assessment in Legal Education: Using Objective-Type Questions to Teach Law

This paper describes how objective online quizzes coupled with extensive feedback can be used as a formative assessment tool to teach doctrine and apply the law to the facts. In particular, this paper encourages instructors to move beyond the use of multiple choice questions and to employ multiple answer, matching, and ordering questions as formative assessment tools.
The United Nation’s Operations in the Former Yugoslavia: Shortcomings in Croatia and Bosnia-Herzegovina

The United Nations made many critical errors during the Yugoslav crisis of the early 1990s. Early inaction was the first critical error made by the UN during the crisis. This error was followed by six other major errors which combined to essentially destroy any chance of success that the UN might have had in the Yugoslav secessionist wars. The UN also allowed the European Community to take charge of the crisis in the initial phases of the conflict. This was a mistake which caused further delay in UN operations in the Croatia and Bosnia-Herzegovina. As a result of these errors, the conflict in the former Yugoslavia was protracted much longer than it might have been had the UN been better prepared to face the challenge. This paper will examine the critical errors made by the UN during the Bosnian and Croatian crises and will propose possible solutions to this particular peacekeeping dilemma and ways that the UN can learn from their mistakes to benefit future peacekeeping missions.
A case of acyclovir neurotoxicity presenting with atypical cerebrospinal fluid findings

An 82-year-old man with a history of end-stage renal disease presented with progressively worsening confusion and somnolence for the past 4–5 days. The patient was diagnosed with herpes zoster by his primary care physician 5 days ago and was started on a course of valacyclovir 1 g three times a day (dose not adjusted for renal impairment). A lumbar puncture was performed and cerebrospinal fluid (CSF) studies revealed 37 white blood cells (WBCs)/hpf (100% monocytes), protein 64 mg/dL and glucose 52 mg/dL. He was started on ceftriaxone, ampicillin and acyclovir. MRI of the brain was done and was unremarkable. Acyclovir-induced encephalopathy was high on differential, but his CSF findings were concerning for viral encephalitis. Nonetheless, all antimicrobials were discontinued and he was scheduled for a 5-hour dialysis session. The very next day, he showed immense improvement and eventually recovered completely. CSF PCR tests for both herpes simplex virus and varicella zoster virus came back negative.
Note: Single ion imaging and fluorescence collection with a parabolic mirror trap

Efficient fluorescence collection is the most challenging part in remote entangled ion qubit state generation. To address this issue, we developed an ion trap consisting of a reflective parabolic surface and a needle electrode. This parabolic trap design covers a solid angle of 2π steradians and allows precise ion placement at the focal point of the parabola. We measured (39 ± 3)% fluorescence collection from a single ion with this trap and analyzed the mirror optical performance. We observed single ion image spot size of 3.4 times diffraction limit, improved to 2.8 times diffraction limit with the help of an external deformable mirror. The micromotion of the ion is determined to be the limiting factor, and the result is consistent with theoretical calculation.
Molecular Recognition in the Colloidal World

ConspectusColloidal self-assembly is a bottom-up technique to fabricate functional nanomaterials, with paramount interest stemming from programmable assembly of smaller building blocks into dynamic crystalline domains and photonic materials. Multiple established colloidal platforms feature diverse shapes and bonding interactions, while achieving specific orientations along with short- and long-range order. A major impediment to their universal use as building blocks for predesigned architectures is the inability to precisely dictate and control particle functionalization and concomitant reversible self-assembly. Progress in colloidal self-assembly necessitates the development of strategies that endow bonding specificity and directionality within assemblies. Methodologies that emulate molecular and polymeric three-dimensional (3D) architectures feature elements of covalent bonding, while high-fidelity molecular recognition events have been installed to realize responsive reconfigurable assemblies. The emer...
Deaf and Hard-of-Hearing Perspectives on Imperfect Automatic Speech Recognition for Captioning One-on-One Meetings

Recent advances in Automatic Speech Recognition (ASR) have made this technology a potential solution for transcribing audio input in real-time for people who are Deaf or Hard of Hearing (DHH). However, ASR is imperfect; users must cope with errors in the output. While some prior research has studied ASR-generated transcriptions to provide captions for DHH people, there has not been a systematic study of how to best present captions that may include errors from ASR software nor how to make use of the ASR system's word-level confidence. We conducted two studies, with 21 and 107 DHH participants, to compare various methods of visually presenting the ASR output with certainty values. Participants answered subjective preference questions and provided feedback on how ASR captioning could be used with confidence display markup. Users preferred captioning styles with which they were already most familiar (that did not display confidence information), and they were concerned about the accuracy of ASR systems. While they expressed interest in systems that display word confidence during captions, they were concerned that text appearance changes may be distracting. The findings of this study should be useful for researchers and companies developing automated captioning systems for DHH users.
A new allocation methodology for recovering transmission investment cost

We propose a new methodology for allocating a period's economic transmission revenue requirement (ETRR) to the users withdrawing power at each of the network's buses. The users' charges are proportional to the amount of their withdrawals and the marginal value of the locational marginal price (LMP) of the buses where the power is withdrawn. The marginal LMP is the difference between the LMPs before and after the addition of the transmission investments. The proposed cost allocation methodology adheres to the six transmission cost allocation principles outlined in the U.S. Federal Energy Regulatory Commission (FERC) order No. 1000. The IEEE 24-bus system is used for demonstrating the affinity of the proposed methodology.
The geometry of the elementary catastrophes: (3). The Parabolic Umbilic

The Behavior Space of the Parabolic Umbilic is two dimensional and the full geometry of this Umbilic Catastrophe is essentially six-dimensional. This paper describes the geometry of both the non-compact and compact versions of the Parabolic Umbilic.
Novel method for hybrid gas-dust cloud ignition using a modified standard minimum ignition energy device

Abstract Hybrid dust-gas explosions are a persistent problem in the process industries because of their low ignition energy and serious consequences. The probability of ignition of a hybrid dust-gas mixture is quantified by its minimum ignition energy (MIE). This study aims at improving the MIE measurement of hybrid dust-gas systems using a modified Kuhner MIKE3 MIE apparatus. The modification includes an add-on device in order to purge the Hartmann tube with the gas of the hybrid mixture before the dust dispersion and ignition attempt. This ensures the gas composition in the Hartmann tube is the same as that of the gas used for dispersing the dust. In this study, the MIE for a hybrid system consisting of Pittsburgh Pulverized Coal (PPC), methane and air was examined. MIE testing was conducted for the two cases: case (a) followed the ASTM E2019-03 standard procedure, while case (b) applied a pre-dispersion purge of the Hartmann tube with the methane-air mixture. In addition, this hybrid system MIE study was conducted with two different particle sizes of PPC, having equivalent polydispersity. Certified cylinders consisting of methane (1, 2, and 3 vol %) blended with ultra-high purity (UHP) air (21.00% oxygen and 79.00% nitrogen) were used. Significant differences in the MIE values of the hybrid dust-gas system were found between the two cases for both particle sizes. The hybrid MIE values obtained with a pre-dispersion purge of the Hartmann tube were found to be lower than those without the purge (which is the most common testing approach); while a smaller particle size also resulted in a lower hybrid MIE. Additionally, it was found that for experiments with or without pre-dispersion purge, and for both particle sizes, the greater the methane concentration, the lower the MIE. This study proves that many of the previous hybrid MIE studies in the Hartmann tube are non-conservative. Future studies should be conducted by including a pre-dispersion purge in the testing procedure. This work lays the foundation for improving the existing ASTM E2019-03 or developing a standalone standard for hybrid dust-gas system MIE testing.
Specialty-care access for community health clinic patients: processes and barriers.

Introduction Community health clinics/centers (CHCs) comprise the US's core health-safety net and provide primary care to anyone who walks through their doors. However, access to specialty care for CHC patients is a big challenge. Materials and methods In this descriptive qualitative study, semistructured interviews of 37 referral coordinators of CHCs were used to describe their perspectives on processes and barriers to patients' access to specialty care. Analysis of data was done using content analysis. Results The process of coordinating care referrals for CHC patients is complex and begins with a provider's order for consultation and ends when the referring provider receives the specialist's note. Poverty, specialist and referral coordinator shortages, lack of insurance, insurance acceptability by providers, transport and clinic-location factors, lack of clinic-hospital affiliations, and poor communication between primary and specialty providers constitute critical barriers to specialty-care access for patients. Conclusion Understanding the complexities of specialty-care coordination processes and access helps determine the need for comprehensive and uninterrupted access to quality health care for vulnerable populations. Guaranteed access to primary care at CHCs has not translated into improved access to specialty care. It is critical that effective policies be pursued to address the barriers and minimize interruptions in care, and to ensure continuity of care for all patients needing specialty care.
Knockout of the Gnrh genes in zebrafish: effects on reproduction and potential compensation by reproductive and feeding-related neuropeptides

Gonadotropin-releasing hormone (GNRH) is known as a pivotal upstream regulator of reproduction in vertebrates. However, reproduction is not compromised in the hypophysiotropic Gnrh3 knockout line in zebrafish (gnrh3-/-). In order to determine if Gnrh2, the only other Gnrh isoform in zebrafish brains, is compensating for the loss of Gnrh3, we generated a double Gnrh knockout zebrafish line. Surprisingly, the loss of both Gnrh isoforms resulted in no major impact on reproduction, indicating that a compensatory response, outside of the Gnrh system, was evoked. A plethora of factors acting along the reproductive hypothalamus-pituitary axis were evaluated as possible compensators based on neuroanatomical and differential gene expression studies. In addition, we also examined the involvement of feeding factors in the brain as potential compensators for Gnrh2, which has known anorexigenic effects. We found that the double knockout fish exhibited upregulation of several genes in the brain, specifically gonadotropin-inhibitory hormone (gnih), secretogranin 2 (scg2), tachykinin 3a (tac3a), and pituitary adenylate cyclase-activating peptide 1 (pacap1), and downregulation of agouti-related peptide 1 (agrp1), indicating the compensation occurs outside of Gnrh cells and therefore is a noncell autonomous response to the loss of Gnrh. While the differential expression of gnih and agrp1 in the double knockout line was confined to the periventricular nucleus and hypothalamus, respectively, the upregulation of scg2 corresponded with a broader neuronal redistribution in the lateral hypothalamus and hindbrain. In conclusion, our results demonstrate the existence of a redundant reproductive regulatory system that comes into play when Gnrh2 and Gnrh3 are lost.
Cardiovascular Medications in Pregnancy

Pregnancy is associated with clinically significant hemodynamic changes that, when superimposed on preexisting cardiovascular disease, may result in maternal destabilization. Pregnancy itself is associated with unique pathological conditions such as preeclampsia. Management of these conditions frequently requires pharmacological intervention. The chapter will build a foundation for understanding hemodynamic changes in pregnancy upon which a strategy for pharmacological therapy will be superimposed. An understanding of maternal physiology complemented by an understanding of the pharmacodynamic actions of specific drugs and alterations in the pharmacokinetics of those drugs in pregnancy will serve to develop a thoughtful strategy for treating pregnant women.
A Brief History and Future Directions for Permanent, Temporary, and Endoscopic GES

Gastric electrical stimulation (GES) has proved to be an effective therapy for many patients with drug refractory gastroparesis. However, technological developments through which to determine optimal modes and sites of stimulus delivery, baseline assessments from which to tailor stimulation parameters, and less invasive tests that predict clinical outcome with GES are still awaited. This chapter explores what temporary and permanent GES can now achieve, as well as forthcoming developments in GES electrodes, devices, and anatomical mapping and placement.
Citrullination Inactivates Nicotinamide-N-methyltransferase

Nicotinamide- N-methyltransferase (NNMT) catalyzes the irreversible methylation of nicotinamide (NAM) to form N-methyl nicotinamide using S-adenosyl methionine as a methyl donor. NNMT is implicated in several chronic disease conditions, including cancers, kidney disease, cardiovascular disease, and Parkinson's disease. Although phosphorylation of NNMT in gastric tumors is reported, the functional effects of this post-translational modification has not been investigated. We previously reported that citrullination of NNMT by Protein Arginine Deiminases abolished its methyltransferase activity. Herein, we investigate the mechanism of inactivation. Using tandem mass spectrometry, we identified three sites of citrullination in NNMT. With this information in hand, we used a combination of site-directed mutagenesis, kinetics, and circular dichoism experiments to demonstrate that citrullination of R132 leads to a structural perturbation that ultimately promotes NNMT inactivation.
A Bioenergetic Framework for Assessing Soil Organic Matter Persistence

The emerging view of soil organic matter (SOM) persistence asserts that SOM exists as a continuum of organic material, continuously processed by the decomposer community from large biopolymers to small monomers and with increasing oxidation and solubility, protected from decomposition through mineral aggregation and adsorption. Microbial community and ecosystem dynamics regulate the exchange of both nutrients and carbon between the soil and the atmosphere through the mineralization of SOM. Because these ecosystem dynamics are driven by net energy flows, analysis of SOM bioenergetics can provide complementary constraints to SOM models as well as insight into the fundamental conundrum of why thermodynamically unstable organic matter persists in soil. Microbial substrate preference has been shown to depend on the energy status of the potential substrates in terms of energy required and energy returned. Here we propose a framework for assessing the persistence of SOM utilizing thermally determined activation energy (Ea) and energy density (ED), tested on a suite of soils that have undergone alteration in field or laboratory experiments designed to isolate persistent SOM. Comparison of these energetic parameters in this framework will determine whether a chemical or physical change during SOM decomposition resulted in a change in its environmental persistence. An expanded framework of bioenergetics changes during SOM formation, decomposition, and stabilization is proposed as persistent SOM is characterized by decreased ED and Ea, relative to the bulk SOM.
What Does Higher Education Need: Revolution And/Or Reform?

The New Education: How to Revolutionize the University to Prepare Students for A World in Flux, by Cathy N. Davidson. New York, NY: Basic Books, 2017, 336 pages. $28.00 Hardcover; $16.99 E-book.The...
Randomized controlled trial of a facilitated online positive emotion regulation intervention for dementia caregivers.

OBJECTIVE To test the effects of Life Enhancing Activities for Family Caregivers (LEAF), a 6-week positive emotion regulation intervention, on outcomes of positive emotion, depression, anxiety, and physical health as measured by the Patient-Reported Outcomes Measurement Information System® (PROMIS®). METHOD A randomized controlled trial (N = 170) comparing LEAF (N = 86) to an emotion reporting/waitlist condition (N = 84) in dementia caregivers. LEAF was individually delivered online by trained facilitators. Participants in the control condition completed daily online emotion reports and then crossed over into the intervention condition after 6 weeks. The study was registered with Clinicaltrials.gov (NCT01825681) and funded by R01NR014435. RESULTS Analyses of difference in change from baseline to 6 weeks demonstrated significantly greater decreases in PROMIS® depression (d = -.25; p = .02) and Quality of Life in Neurological Disorders (NeuroQOL) anxiety (d = -.33; p < .01), as well as improvements in PROMIS® physical health (d = .24; p = .02) in the intervention condition compared to the emotion reporting/waitlist control. The intervention also showed greater improvements in positive emotion (d = .58; p < .01) and positive aspects of caregiving (d = .36; p < .01). Increases in positive emotion significantly mediated the effect of LEAF on depression over time. CONCLUSIONS This randomized controlled trial of the online-facilitated positive emotion regulation intervention in dementia caregivers demonstrated small to medium effect sizes on caregiver well-being and shows promise for remotely delivered programs to improve psychological well-being in caregivers of people with dementia and other chronic illnesses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Migrant youth from West African countries enacting affective citizenship

Civic education is critical to the preparation of migrant youth for democratic living by instilling in them a sense of belonging to the polity. However, liberal conceptions of the citizen as a rati...
Effect of Light Intensity on Regulation of Melatonin Secretion and Drinking Behavior in the Albino Rat

ABSTRACT Melatonin was measured in the urine of rats exposed to lighting regimens of varying intensities. Water consumption was monitored concurrently. The results show : (1) The amplitude of the free-running urinary melatonin rhythm is diminished among animals exposed to constant illumination; the magnitude of this effect is a function of the intensity of the light. The constant irradiance that produces a 50% decrease in the amplitude of the urinary melatonin rhythm has been calculated to be about 0.03 μW/cm2. (2) The rate of entrainment of the rhythms of both melatonin excretion and water consumption to diurnal lighting is dependent on the intensity differential between the light and the dark phase: the greater the differential, the more quickly both the melatonin and the drinking rhythms entrain to the lighting regimen.
Integration of probabilistic regulatory networks into constraint-based models of metabolism with applications to Alzheimer’s disease

Mathematical models of biological networks can provide important predictions and insights into complex disease. Constraint-based models of cellular metabolism and probabilistic models of gene regulatory networks are two distinct areas that have progressed rapidly in parallel over the past decade. In principle, gene regulatory networks and metabolic networks underly the same complex phenotypes and diseases. However, systematic integration of these two model systems remains a fundamental challenge. In this work, we address this challenge by fusing probabilistic models of gene regulatory networks into constraint-based models of metabolism. The novel approach utilizes probabilistic reasoning in BN models of regulatory networks serves as the “glue” that enables a natural interface between the two systems. Probabilistic reasoning is used to predict and quantify system-wide effects of perturbation to the regulatory network in the form of constraints for flux variability analysis. In this setting, both regulatory and metabolic networks inherently account for uncertainty. Applications leverage constraint-based metabolic models of brain metabolism and gene regulatory networks parameterized by gene expression data from the hippocampus to investigate the role of the HIF-1 pathway in Alzheimer’s disease. Integrated models support HIF-1A as effective target to reduce the effects of hypoxia in Alzheimer’s disease. However, HIF-1A activation is far less effective in shifting metabolism when compared to brain metabolism in healthy controls. The direct integration of probabilistic regulatory networks into constraint-based models of metabolism provides novel insights into how perturbations in the regulatory network may influence metabolic states. Predictive modeling of enzymatic activity can be facilitated using probabilistic reasoning, thereby extending the predictive capacity of the network. This framework for model integration is generalizable to other systems.
Health Service Use Among Chinese American Older Adults: Is There a Somatization Effect?

Background/objectives Somatization of depressive symptoms among Chinese American older adults remains understudied. This study aimed to identify whether the relationship between depressive symptoms and use of health services (ie, doctor visits, hospital, and emergency department) could be due to pain and whether acculturation played a role in the relations among depressive symptoms, pain, and health service use. Design and participants Secondary data came from the Population Study of Chinese Elderly in Chicago that surveyed 3159 Chinese community-dwelling older adults in the greater Chicago area. The average age was 76.3 years (standard deviation = 8.4); 57.95% were female). Negative binominal models were used to identify the effects of depression and pain on each type of health service use, controlling for sociodemographics and health-related factors (eg, chronic illness). Measurements Depressive symptoms were assessed using the Patient Health Questionnaire-9; pain was assessed by self-reported pain severity. Participants were classified into low, moderate, and high acculturation groups based on acculturation scores. Results Depressive symptoms and pain were positively related to health service use on the bivariate level. For groups with both low and high acculturation levels, depression and pain each independently predicted more health service use, whereas for the group with a moderate acculturation level, the effect of somatization was substantialized. Conclusion Depression largely influenced health service use independently and partially through pain for older Chinese Americans. The somatization tended to be only salient for the moderate acculturation group, calling for more research attention to the complicated effect of acculturation. J Am Geriatr Soc 67:S584-S589, 2019.
Most cancers carry a substantial deleterious load due to Hill-Robertson interference

Abstract Introduction Cancer genomes exhibit surprisingly weak signatures of negative selection1,2. This may be because tumors evolve either under very weak selective pressures (‘weak selection’) or under conditions that prevent the elimination of many deleterious passenger mutations (‘poor efficacy of selection’)xs. Rationale The weak selection model argues that the majority of genes are only important for multicellular function. The poor efficacy of selection model argues, in contrast, that genome-wide linkage in cancer prevents many deleterious mutations from being removed via Hill-Robertson interference3. Since these linkage effects weaken as mutation rates decrease, we predict that cancers with lower mutational burdens should exhibit stronger signals of negative selection. Furthermore, because linkage affects driver mutations as well, low mutational burden cancers should also show stronger evidence of positive selection in driver genes. Neither pattern — in drivers or passengers — is expected under the weak selection model. We leverage the 10,000-fold variation in mutational burden across cancer subtypes to stratify tumors by their genome-wide mutational burden and used a normalized ratio of nonsynonymous to synonymous substitutions (dN/dS) to quantify the extent that selection varies with mutation rate. Results We find that appreciable negative selection (dN/dS ~ 0.4) is present in tumors with a low mutational burden, while the remaining cancers (96%) exhibit dN/dS ratios approaching 1, suggesting that the majority of tumors do not remove deleterious passengers. A parallel pattern is seen in drivers, where positive selection attenuates as the mutational burden of cancers increases. Both trends persist across tumor-types, are not exclusive to essential or housekeeping genes, and are present in clonal and subclonal mutations. Two additional orthogonal lines of evidence support the weak efficacy model: passengers are less damaging in low mutational burden cancers, and patterns of attenuated selection also emerge in Copy Number Alterations. Finally, we find that an evolutionary model incorporating Hill-Robertson interference can reproduce both patterns of attenuated selection in drivers and passengers if the average fitness cost of passengers is 1.0% and the average fitness benefit of drivers is 19%. Conclusion Collectively, our findings suggest that the lack of signals of negative selection in most tumors is not due to relaxed selective pressures, but rather the inability of selection to remove individual deleterious mutations in the presence of genome-wide linkage. As a result, despite the weak individual fitness effects of passengers, most cancers harbor a large mutational load (median ~40% total fitness cost) and succeed due to acquisition of additional strong drivers (~5 with an overall benefit of ~130%). Understanding how this deleterious load is overcome may help identify cancer vulnerabilities that may be targeted by new and existing therapies.
Evaluation of Athletes with Neck or Arm Pain

The symptoms of cervical spine and upper extremity injuries often overlap, which requires providers to distinguish between the two in order to accurately diagnose. Differentiating between the two involves a strong understanding of the neurologic exam, peripheral exam findings, and myotomal/dermatomal findings correlative to cervical spine levels. The most common dilemma encountered by providers assessing athletes with neck and arm pain is differentiating radicular symptoms from cervical pathology and musculoskeletal injuries. The diagnostic challenge is addressed by formulating a broad differential diagnosis and utilizing the physical exam and history to achieve a correct diagnosis.
The negativity bias, revisited: Evidence from neuroscience measures and an individual differences approach

Past research has provided support for the existence of a negativity bias, the tendency for negativity to have a stronger impact than positivity. Theoretically, the negativity bias provides an evolutionary advantage, as it is more critical for survival to avoid a harmful stimulus than to pursue a potentially helpful one. The current paper reviews the theoretical grounding of the negativity bias in the Evaluative Space Model, and presents recent findings using a multilevel approach that further elucidate the mechanisms underlying the negativity bias and underscore the importance of the negativity bias for human functioning.
Trace elements in Cr-pyrope from the Navajo volcanic field of the Colorado Plateau, SW USA, and implications for the mantle wedge during low-angle subduction

Abstract The zonation of trace elements in Cr-pyrope has been analyzed to investigate histories recorded by garnet in cool mantle and implications for processes in the mantle wedge during low-angle subduction. The garnets are from the Navajo Volcanic Field (NVF) of the Colorado Plateau in the southwestern United States. Their host rocks were emplaced between 30 and 24 Ma, not long after low-angle subduction of the Farallon plate and the Laramide orogeny. Twenty-seven of the 31 garnets are discrete fragments from diatremes of serpentinized ultramafic microbreccia (SUM). Many Ni and Mn values in those grains yield temperatures in and below the range 800 °C to 600 °C, consistent with inclusions of chlorite and other hydrous minerals. Gradients of Na, Ti, Mn, Ni, Y, REE, and other elements are common in the discrete grains. Diffusion calculations constrain possible histories of a garnet with growth zonation of Y and REE and retrograde zonation of Mn and Ni. The garnet must have formed and resided at temperatures below about 900 °C, and that zonation is unlikely to have been preserved from the Proterozoic. The Mn gradient is consistent with cooling during the time period of low-angle Farallon subduction. Many of the discrete garnets grew from sources metasomatically enriched in Li, Na, Ti, and Zr, and they have distinctive high Li/Na. The high Li/Na is a likely consequence of Li metasomatism in the mantle wedge. Nb values in the Cr-pyrope fragments from northern SUM diatremes are lower than those of most garnets from kimberlites, but the low values are similar to and lower than those of pyrope in peridotite emplaced in orogenic belts; those northern diatremes also host lawsonite eclogite and garnetite. Most but not all relatively Cr-rich discrete garnets (4 to 8 wt% Cr2O3) record enrichment in LREE but little enrichment in Ti and Zr; LREE enrichment by an aqueous fluid is consistent with chlorite inclusions in two of these garnets. Oriented lamellae of rutile and other phases are common, and one texture may record fluid interactions associated with interface-coupled dissolution-reprecipitation. Garnets from the four minette-hosted peridotites record markedly hotter temperatures than do the SUM-hosted grains, and they lack the high Li/Na and low Nb. Gradients of trace elements in minette-hosted garnets record metasomatism shortly before crustal emplacement, but that metasomatism resulted in a decrease of Nb and had little effect on Li/Na. The minette-hosted garnet peridotites may represent mantle residual from Proterozoic accretion of the Colorado Plateau. In contrast, at least some of the SUM-hosted garnets probably grew in rock eroded from the forearc wedge by low-angle subduction and emplaced below the NVF.
A note on modeling placement values in the analysis of receiver operating characteristic curves

Recent advances in receiver operating characteristic (ROC) curve analyses advocate modeling of placement value (PV), a quantity that measures the position of diseased test scores relative to the he...
Discretize-Optimize vs. Optimize-Discretize for Time-Series Regression and Continuous Normalizing Flows.

We compare the discretize-optimize (Disc-Opt) and optimize-discretize (Opt-Disc) approaches for time-series regression and continuous normalizing flows (CNFs) using neural ODEs. Neural ODEs are ordinary differential equations (ODEs) with neural network components. Training a neural ODE is an optimal control problem where the weights are the controls and the hidden features are the states. Every training iteration involves solving an ODE forward and another backward in time, which can require large amounts of computation, time, and memory. Comparing the Opt-Disc and Disc-Opt approaches in image classification tasks, Gholami et al. (2019) suggest that Disc-Opt is preferable due to the guaranteed accuracy of gradients. In this paper, we extend the comparison to neural ODEs for time-series regression and CNFs. Unlike in classification, meaningful models in these tasks must also satisfy additional requirements beyond accurate final-time output, e.g., the invertibility of the CNF. Through our numerical experiments, we demonstrate that with careful numerical treatment, Disc-Opt methods can achieve similar performance as Opt-Disc at inference with drastically reduced training costs. Disc-Opt reduced costs in six out of seven separate problems with training time reduction ranging from 39% to 97%, and in one case, Disc-Opt reduced training from nine days to less than one day.
Conversational Coordination of Articulation Responds to Context: A Clinical Test Case with Traumatic Brain Injury.

Purpose Coordination of communicative behavior supports shared understanding in conversation. The current study brings together analysis of two speech coordination strategies, entrainment and compe...
Loneliness in pregnant and postpartum people and parents of children aged 5 years or younger: a scoping review protocol.

The experience of loneliness during pregnancy and in new parenthood has not been targeted and developed as a program of research, despite evidence indicating that the incidence of loneliness is highest in those aged 16 to 24 and that loneliness rises during transitional periods. The scarcity of parenthood-loneliness inquiries leaves a gap in our understanding of new parenthood and its effects on the health and well-being of parents and their children. Here, a scoping review protocol will be presented to address this gap. The objective of this study will be to summarize the current knowledge of loneliness experienced during pregnancy and by parents during the postpartum period through the first 5 years of the child’s life. A scoping review protocol was designed following Arksey and O’Malley’s framework. We will include all types of literature in English, including all study designs, reviews, opinion articles, dissertations, reports, books, and grey literature. To be considered for inclusion, sources should focus on loneliness in pregnant persons, postpartum people, and parents of children 5 years or younger. We will search the following electronic databases (from inception onwards): MEDLINE, EMBASE, CINAHL Complete, Cochrane Library, PsycINFO, Dissertations & Theses Global, Sociological Abstracts, Scopus, and Web of Science. Grey literature will be identified searching the British governmental website gov.uk, the Jo Cox Commission on Loneliness, the Campaign to End Loneliness, and the British Red Cross’s Action on Loneliness websites. Two reviewers, working independently of each other, will screen the titles and abstracts of the articles returned by the searches, then screen the selected full-text articles, and extract data. A third reviewer will cast the deciding vote in case no consensus is reached. Results will be given in the narrative form, mapped, and illustrated. This scoping review will capture the state of the current literature on loneliness in pregnancy and new parenthood. Results will be published in a peer-reviewed journal. We anticipate that the study will identify gaps and make recommendations for future areas of study and related interventions. The protocol is available on Open Science Framework at DOI 10.17605/OSF.IO/BFVPZ.