Search

The COVID-19 pandemic and related restrictions led to major transit demand decline for many public transit systems in the United States. This paper is a systematic analysis of the dynamics and dimensions of this unprecedented decline. Using transit demand data derived from a widely used transit navigation app, we fit logistic functions to model the decline in daily demand and derive key parameters: base value, the apparent minimal level of demand and cliff and base points, representing the initial date when transit demand decline began and the final date when the decline rate attenuated. Regression analyses reveal that communities with higher proportions of essential workers, vulnerable populations (African American, Hispanic, Female, and people over 45 years old), and more coronavirus Google searches tend to maintain higher levels of minimal demand during COVID-19. Approximately half of the agencies experienced their decline before the local spread of COVID-19 likely began; most of these are in the US Midwest. Almost no transit systems finished their decline periods before local community spread. We also compare hourly demand profiles for each system before and during COVID-19 using ordinary Procrustes distance analysis. The results show substantial departures from typical weekday hourly demand profiles. Our results provide insights into public transit as an essential service during a pandemic.

COVID-19 infection caused by SARS-CoV2 virus is an acute respiratory illness which was declared as a pandemic by the World Health Organization. Usually, SARS-CoV2 infects independently and can cause spectrum of disease ranging from mild illness to severe progressive pneumonia, multiorgan dysfunction, and death; however, co-infections with other respiratory pathogens have been noted. Here, we present 2 fatal cases with co-infection, one with parainfluenza-4 virus and other co-infection/secondary infection with Streptococcus pneumoniae bacteria. Further studies are needed to study the effect of co-infections on morbidity and mortality of patients and establish the outcome of such infections.

Sustainable materials management focuses on the dynamics of materials in economic and environmental activities to optimize material use efficiency and reduce environmental impact. A preliminary web-based information system is thus developed to analyze the issues of resource consumption and waste generation, enabling countries to manage resources and wastes from a life cycle perspective. This pioneering system features a four-layer framework that integrates information on physical flows and economic activities with material flow accounting and waste input–output table analysis. Within this framework, several applications were developed for different waste and resource management stakeholders. The hierarchical and interactive dashboards allow convenient overview of economy-wide material accounts, waste streams, and secondary resource circulation. Furthermore, the system can trace material flows through associated production supply chain and consumption activities. Integrated with economic models; this system can predict the possible overloading on the current waste management facility capacities and provide decision support for designing strategies to approach resource sustainability. The limitations of current system are specified for directing further enhancement of functionalities.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

Summary: Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6. : Mishra et al. demonstrate that IL-6 is produced by lPBN neurons, astrocytes, and microglia. They show that IL-6 acts in the lPBN to reduce body weight by increasing thermogenesis and reducing food intake. They also identify two pathophysiological/physiological contexts, obesity and cold exposure, that divergently affect lPBN IL-6 production. Keywords: lateral PBN, hindbrain, energy balance, cold exposure, obesity, thyroid, brown adipose tissue, diet-induced obesity, sex differences, PVN

Mathematical models of the natural history of disease can predict incidence rates based on prevalence data and support simulations of populations where thyroid function affects other aspects of physiology. We developed a Markov chain model of functional thyroid disease status over the lifetime. Subjects were in one of seven thyroid disease states at any given point in their lives [normal, subclinical hypothyroidism, overt hypothyroidism, treated thyroid disease (ever), subclinical hyperthyroidism, overt hyperthyroidism, and reverted to normal thyroid status]. We used a Bayesian approach to fitting model parameters. A priori probabilities of changing from each disease state to another per unit time were based on published data and summarized using meta-analysis, when possible. The probabilities of changing state were fitted to observed prevalence data based on the National Health and Nutrition Examination Survey 2007-2012. The fitted model provided a satisfactory fit to the observed prevalence data for each disease state, by sex and decade of age. For example, for males 50-59 years old, the observed prevalence of ever having treated thyroid disease was 4.4% and the predicted value was 4.6%. Comparing the incidence rates of treated disease predicted from our model with published values revealed that 82% were within a 4-fold difference. The differences seemed to be systematic and were consistent with expectation based on national iodine intakes. The model provided new and comprehensive estimates of functional thyroid disease incidence rates for the U.S. Because the model provides a reasonable fit to national prevalence data and predicts thyroid disease status over the lifetime, it is suitable for simulating populations, thereby making possible quantitative bias analyses of selected epidemiologic data reporting an association of thyroid disease with serum concentrations of environmental contaminants.

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies.

Social networking sites (SNS) include online products such as Facebook that allow users to build and maintain large interpersonal Internet networks. Older adult users have dramatically increased (Duggan & Smith, 2014). This investigation examined how 212 university undergraduate Facebook users estimated success with helping others use Facebook when learner’s age (20, 40, 60 year olds.) and type of acquaintance (friend or kin) was manipulated in hypothetical scenarios. In these scenarios, a person is identified as KW, described as being a college student much like the participant. KW has 20, 40 or 60 year-old acquaintances, a friend or a kin at each age, all wanting KW’s help learning about social media. This was the only information provided. Qualities and strengths of these interpersonal relationships were not examined. Results from repeated measures 2x3 ANOVA showed a significant main effect for age, but no effect for acquaintance type. Results showed no significant interaction. Although the age demographic above 50 years is the fastest growing SNS group, results showed possible age stereotyping among youth when they assist older adults learning to use SNS. This age effect may be lessened as older adults become more skillful social media users. These findings are limited because of the sample demographics and a lack of identifying qualities of participants’attributions about the hypothetical friends or relatives. Future research using multiple items per condition might be able to further elucidate how the type of associations between helper and learner, close or distant, positive or negative, would influence outcomes.

Based on a critical historical, institutional, and comparative approach, this article discusses the origins of Literacy Studies and their implications for the current debate on the subject. Addressing the meanings that literacy acquires during different time periods, especially the beliefs with which it is associated since at least the Renaissance, the paper addresses false dichotomies and institutional locations referred to by different disciplines and the beliefs and actions related to them. Associated with notions of progress, civilization and social control, literacy is in permanent crisis, which contributes to calls for interdisciplinary studies. Putting into question such terms as written culture and the place of academic disciplines, the article calls for new questions to the advancement of the area.

Historically, it has been difficult for students and their families to compare how different colleges and programs improve students' chances of landing a desirable job and earning a good salary. The U.S. Department of Education's 2015 release of student earning data was a major step toward remedying this problem. The data offered by the College Scorecard (CSC) have facilitated the development of a number of different ranking methodologies that attempt to measure the "value" gained from attending different colleges and programs. This article analyzes five CSC-based systems that measure educational return on investment in various ways. There are important differences in how these methodologies balance the costs of college and median earnings of graduates to assign relative value. Limitations in data granularity prevent important analysis, particularly comparisons of how universities perform with members of underserviced demographic groups.

Previous research by Burnett and Wahl found that resilience moderately mediated the association between compassion fatigue (CF) and burnout (BO) among trauma responders. No studies have attempted to replicate and verify the research results of Burnett and Wahl. This study examined whether similar patterns of resilience, CF, BO, and compassion satisfaction (CS) would be found among a convenience sample of disaster behavioral health (DBH) responders ( N = 70) attending an annual Critical Incident Stress Management training conference in Michigan. Measures included the 30-item Professional Quality of Life Scale, the 14-Item Resilience Scale, the Response to Stressful Events Scale, and a demographic questionnaire. Similar to the Burnett and Wahl’s study, resilience was found to have a significant negative correlation between CF and BO. Mediation analysis similarly found that resilience moderately mediated the relationship between CF and BO among both resilience measures.

Daily use of social networking sites (SNS) such as Facebook has become routine for millions of Internet users. Facebook is currently still the most popular social media site. Social networking has been rapidly adopted by societies around the world. In particular, social media like Facebook provide sites where users can personalize a profile with their information, pictures, and videos that can be shared with other users. This information can be used in ways that may violate users’ privacy with or without their knowledge. The hypotheses were that use of Facebook, user self-efficacy for social media and users’ general attitudes about privacy expectations are predictors of specific attitudes towards Facebook social media privacy, among a sample of 284, mostly white female, undergraduate college students in their twenties. Facebook self-efficacy and Facebook personal privacy violations were significant determinants of general Internet social media privacy concerns. However, Facebook use was not a significant factor for general Internet social media privacy concerns. Perceived benefits of Facebook generally appear to outweigh risks of disclosing personal information.

Accurate prediction of metabolism is a significant outstanding challenge in toxicology. The best predictions are based on experimental data from in vitro systems using primary hepatocytes. The predictivity of the primary hepatocyte-based culture systems, however, is still limited due to well-known phenotypic instability and rapid decline of metabolic competence within a few hours. Dynamic flow bioreactors for three-dimensional cell cultures are thought to be better at recapitulating tissue microenvironments and show potential to improve in vivo extrapolations of chemical or drug toxicity based on in vitro test results. These more physiologically relevant culture systems hold potential for extending metabolic competence of primary hepatocyte cultures as well. In this investigation, we used computational fluid dynamics (CFD) to determine the optimal design of a flow-based hepatocyte culture system for evaluating chemical metabolism in vitro. The main design goals were 1) minimization of shear stress experienced by the cells to maximize viability, 2) rapid establishment of a uniform distribution of test compound in the chamber, and 3) delivery of sufficient oxygen to cells to support aerobic respiration. Two commercially available flow devices — RealBio® (RB) and QuasiVivo® (QV) — and a custom developed fluidized bed (FB) bioreactor were simulated, and turbulence, flow characteristics, test compound distribution, oxygen distribution, and cellular oxygen consumption were analyzed. Experimental results from the bioreactors were used to validate the simulation results.Our results indicate that maintaining adequate oxygen supply is the most important factor to the long-term viability of liver bioreactor cultures. Cell density and system flow patterns were the major determinants of local oxygen concentrations. The experimental results closely corresponded to the in silico predictions. Of the three bioreactors examined in this study, we were able to optimize the experimental conditions for long-term hepatocyte cell culture using the QV bioreactor. This system facilitated the use of low system volumes coupled with higher flow rates. This design supports cellular respiration by increasing oxygen concentrations in the vicinity of the cells, and facilitates long-term kinetic studies of low clearance test compounds. These two goals were achieved while simultaneously keeping the shear stress experienced by the cells within acceptable limits.

Abstract Methodologies for integrating (weighing) evidence and assessing uncertainties are of utmost importance to ensure that scientific assessments are transparent, robust and fit for purpose to support decision‐makers. One of the key challenges remains the development of harmonised methodologies for both weighing scientific evidence and assessing uncertainties in the food safety area mainly because of the multidisciplinary and complex nature of the topics involved. The breakout session ‘Weighing evidence and assessing uncertainties’ was held at the EFSA 2nd Scientific Conference ‘Shaping the Future of Food Safety, Together’. This paper aims at summarising the contributions of this breakout session and formulates recommendations to further support the development of harmonised methodologies and practical applications for weighing evidence and analysing uncertainty in key areas of food safety, including chemical risk assessment, microbiological risk assessment and environmental risk assessment.

Com base em uma abordagem histórica, institucional e comparativa, discute-se neste artigo a origem dos estudos sobre letramento e suas consequências para o atual debate sobre o tema. Analisam-se os significados que o letramento adquire em cada época, destacando-se as crenças que nele são postas desde, pelo menos, a Renascença, e trabalham-se as cisões, as falsas dicotomias e os lugares institucionais em relação às disciplinas que dele se ocupam e às ações-práticas a ele relacionadas. Associado a noções de progresso, civilização e controle social, o letramento está em constante crise, o que contribui para fazer avançar estudos interdisciplinares. Questionando termos como cultura escrita e o lugar das disciplinas acadêmicas, o texto convoca a fazer novas perguntas para o avanço da área.

Climate change and decadal variability are impacting marine fish and invertebrate species worldwide and these impacts will continue for the foreseeable future. Quantitative approaches have been developed to examine climate impacts on productivity, abundance, and distribution of various marine fish and invertebrate species. However, it is difficult to apply these approaches to large numbers of species owing to the lack of mechanistic understanding sufficient for quantitative analyses, as well as the lack of scientific infrastructure to support these more detailed studies. Vulnerability assessments provide a framework for evaluating climate impacts over a broad range of species with existing information. These methods combine the exposure of a species to a stressor (climate change and decadal variability) and the sensitivity of species to the stressor. These two components are then combined to estimate an overall vulnerability. Quantitative data are used when available, but qualitative information and expert opinion are used when quantitative data is lacking. Here we conduct a climate vulnerability assessment on 82 fish and invertebrate species in the Northeast U.S. Shelf including exploited, forage, and protected species. We define climate vulnerability as the extent to which abundance or productivity of a species in the region could be impacted by climate change and decadal variability. We find that the overall climate vulnerability is high to very high for approximately half the species assessed; diadromous and benthic invertebrate species exhibit the greatest vulnerability. In addition, the majority of species included in the assessment have a high potential for a change in distribution in response to projected changes in climate. Negative effects of climate change are expected for approximately half of the species assessed, but some species are expected to be positively affected (e.g., increase in productivity or move into the region). These results will inform research and management activities related to understanding and adapting marine fisheries management and conservation to climate change and decadal variability.

Resistance to intravenous immunoglobulin (IVIG) occurs in 10-20% of patients with Kawasaki disease (KD). The risk of resistance is about two-fold higher in patients with elevated gamma glutamyl transferase (GGT) levels. We sought to understand the biological mechanisms underlying IVIG resistance in patients with elevated GGT levels.We explored the association between elevated GGT levels and IVIG-resistance with a cohort of 686 KD patients (Cohort I). Gene expression data from 130 children with acute KD (Cohort II) were analyzed using the R square statistic and false discovery analysis to identify genes that were differentially represented in patients with elevated GGT levels with regard to IVIG responsiveness. Two additional KD cohorts (Cohort III and IV) were used to test the hypothesis that sialylation and GGT may be involved in IVIG resistance through neutrophil apoptosis.Thirty-six genes were identified that significantly explained the variations of both GGT levels and IVIG responsiveness in KD patients. After Bonferroni correction, significant associations with IVIG resistance persisted for 12 out of 36 genes among patients with elevated GGT levels and none among patients with normal GGT levels. With the discovery of ST6GALNAC3, a sialyltransferase, as the most differentially expressed gene, we hypothesized that sialylation and GGT are involved in IVIG resistance through neutrophil apoptosis. We then confirmed that in Cohort III and IV there was significantly less reduction in neutrophil count in IVIG non-responders.Gene expression analyses combining molecular and clinical datasets support the hypotheses that: (1) neutrophil apoptosis induced by IVIG may be a mechanism of action of IVIG in KD; (2) changes in sialylation and GGT level in KD patients may contribute synergistically to IVIG resistance through blocking IVIG-induced neutrophil apoptosis. These findings have implications for understanding the mechanism of action in IVIG resistance, and possibly for development of novel therapeutics.

Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses.Demographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision-tree-based KD diagnostic algorithm.This KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients.The colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness.

BACKGROUND:Kawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states. MATERIALS AND METHODS:Plasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI) mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different. RESULTS:A mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003) and FC (p = 7.9 x 10-10) subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD-associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects. CONCLUSIONS:Using SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD.

The American cranberry (Vaccinium macrocarpon Ait.) contains rich antioxidants and has significant health benefits in fighting a variety of human diseases. In the past ten years, cranberry growers have reported yellow vine syndrome, which is associated with reduced photosynthetic performance, in the cranberry bogs. It has been found that the yellow vine syndrome of cranberry is associated with nutritional imbalance; it might be an issue for cranberry quality and food security as well as the crop production. This review evaluates the present state of knowledge of yellow vine syndrome, together with recent advances that are resulting from an improved mechanistic understanding and a possible solution that will be of considerable value to cranberry growers. This review also includes results from the author’s own laboratory. Water stress, nutritional imbalance, and photoinhibition are the likely reasons for producing yellow vine of cranberry. Future endeavors should be placed on the combination of genetic, biochemical, and biophysical techniques at the molecular level and plant physiology at the field and greenhouse level. This may provide specific information in order to understand the molecular details of yellow vine of cranberry as well as a tool for guiding future breeding efforts and management practices.

Background: Frail hospitalized older adults are at risk for adverse outcomes. Previous studies have suggested benefits for inpatient geriatric management (GEM). We sought to determine whether hospitalized patients with a history of heart failure (HF) benefitted from inpatient GEM or not. Methods: We studied 309 inpatients previously diagnosed with HF who were participants in a randomized trial of geriatric evaluation and management (GEM) versus usual care (UC). The intervention involved multidisciplinary teams that provided comprehensive geriatric assessment. We evaluated health-related quality of life (HRQOL), basic activities of daily living (ADLs), health service utilization, and survival at discharge, 6 months, and 1 year post randomization. Results: GEM patients had higher mean change scores for physical function (unadjusted means: 0.17 vs. –4.67, p = 0.046) and basic ADLs (1.25 vs. 0.67, p = 0.003) at hospital discharge, which remained significant after adjusting for baseline HRQOL scores and in-hospital days. Outcomes were not significantly different at 1 year. Length of stay for GEM was greater than UC (24 days vs. 17 days, p = 0.03), but total costs at 1 year were not different (p = 0.9). Mortality rates at 1 year were high and similar (GEM 29.0%, UC 27.3%, p = 0.73) in both the groups. Conclusion: Inpatient GEM was associated with better maintenance of physical function and basic ADLs at hospital discharge; however, no differences in HRQOL or survival were observed between GEM and UC at 1 year post randomization. Restructuring inpatient care models to incorporate inpatient GEM principles may be one method to optimize health-care delivery.

There is increasing emphasis on active transportation, such as walking, in transportation planning as a sustainable form of mobility and in public health as a means of achieving recommended physical activity and better health outcomes. A research focus is the influence of the built environment on walking, with the ultimate goal of identifying environmental modifications that invite more walking. A key issue is determining the spatial units for walkability measures so that they reflect potential walking behavior. This paper develops methods for assessing walkability within individual activity spaces: the geographic region accessible to an individual during a given walking trip. Based on objective walkability measures of the street blocks, we use three summary measures for walkability within activity spaces: i) the average walkability score across block segments, ii) the standard deviation, and iii) the network autocorrelation. We assess the method using data from an empirical study of built environment walkability and walking behavior in Salt Lake City, Utah. We visualize these activity-space summary measures to compare walkability among individuals’ trips within their neighborhoods. We also compare summary measures for activity spaces versus Census block groups, with the result that they agree less than half of the time.

Many studies have documented long-term changes in adult marine fish distributions and linked these changes to climate change and multi-decadal climate variability. Most marine fish, however, have complex life histories with morphologically distinct stages, which use different habitats. Shifts in distribution of one stage may affect the connectivity between life stages and thereby impact population processes including spawning and recruitment. Specifically, many marine fish species have a planktonic larval stage, which lasts from weeks to months. We compared the spatial distribution and seasonal occurrence of larval fish in the Northeast U.S. Shelf Ecosystem to test whether spatial and temporal distributions changed between two decades. Two large-scale ichthyoplankton programs sampled using similar methods and spatial domain each decade. Adult distributions from a long-term bottom trawl survey over the same time period and spatial area were also analyzed using the same analytical framework to compare changes in larval and adult distributions between the two decades. Changes in spatial distribution of larvae occurred for 43% of taxa, with shifts predominately northward (i.e., along-shelf). Timing of larval occurrence shifted for 49% of the larval taxa, with shifts evenly split between occurring earlier and later in the season. Where both larvae and adults of the same species were analyzed, 48% exhibited different shifts between larval and adult stages. Overall, these results demonstrate that larval fish distributions are changing in the ecosystem. The spatial changes are largely consistent with expectations from a changing climate. The temporal changes are more complex, indicating we need a better understanding of reproductive timing of fishes in the ecosystem. These changes may impact population productivity through changes in life history connectivity and recruitment, and add to the accumulating evidence for changes in the Northeast U.S. Shelf Ecosystem with potential to impact fisheries and other ecosystem services.

Trajectories of perceived stress from the transition to adulthood (age 25), during young adulthood (age 32), and into midlife (ages 43 and 50) were examined with four waves of longitudinal survey data (N = 688; 49% female, 37% with a university degree, 86% White). We explored how between- and within-person variation in perceived stress was associated with age 50 psychological well-being (life satisfaction and eudaimonic well-being), self-reported physical health, career satisfaction, and intimate partnership satisfaction. Growth curve analyses revealed stress followed a linear decreasing trajectory from the transition to adulthood into midlife with substantial variability underlying the average pattern. Between- and within-person variation in perceived stress was associated with midlife functioning. Those with lower initial levels of and more decline in perceived stress reported better psychological and physical health and higher relationship satisfaction at age 50 compared to those with initially higher perceived stress and less decline over time. Higher than one's own average perceived stress at ages 25, 32, 43, and 50 years was associated with lower psychological and physical health and intimate partnership satisfaction at age 50. These results support key contentions of developmental theory and may prove useful when designing interventions aimed at promoting well-being in midlife.

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting.MethodsIn this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals.Findings1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0-99·3) in the first stage and 96·0% (95·6-97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital.InterpretationKIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications.FundingUS Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

PurposeSeveral studies have reported sleep disturbances during the COVID-19 virus pandemic. Little data exist about the impact of the pandemic on sleep and mental health among older women with breast cancer. We sought to examine whether women with and without breast cancer who experienced new sleep problems during the pandemic had worsening depression and anxiety.MethodsBreast cancer survivors aged ≥60 years with a history of nonmetastatic breast cancer (n = 242) and frequency-matched noncancer controls (n = 158) active in a longitudinal cohort study completed a COVID-19 virus pandemic survey from May to September 2020 (response rate 83%). Incident sleep disturbance was measured using the restless sleep item from the Center for Epidemiological Studies-Depression Scale (CES-D). CES-D score (minus the sleep item) captured depressive symptoms; the State-Anxiety subscale of the State Trait Anxiety Inventory measured anxiety symptoms. Multivariable linear regression models examined how the development of sleep disturbance affected changes in depressive or anxiety symptoms from the most recent prepandemic survey to the pandemic survey, controlling for covariates.ResultsThe prevalence of sleep disturbance during the pandemic was 22.3%, with incident sleep disturbance in 10% and 13.5% of survivors and controls, respectively. Depressive and anxiety symptoms significantly increased during the pandemic among women with incident sleep disturbance (vs. no disturbance) (β = 8.16, p

Binocular vision is a visual property that allows fine discrimination of in-depth distance (stereopsis), as well as enhanced light and contrast sensitivity. In mammals enhanced binocular vision is structurally associated with a large degree of frontal binocular overlap, the presence of a corresponding retinal specialization containing a fovea or an area centralis, and well-developed ipsilateral retinal projections to the lateral thalamus (GLd). We compared these visual traits in two visually active species of the genus Octodon that exhibit contrasting visual habits: the diurnal Octodon degus, and the nocturnal Octodon lunatus. The O. lunatus visual field has a prominent 100° frontal binocular overlap, much larger than the 50° of overlap found in O. degus. Cells in the retinal ganglion cell layer were 40% fewer in O. lunatus (180,000) than in O. degus (300,000). O. lunatus has a poorly developed visual streak, but a well developed area centralis, located centrally near the optic disk (peak density of 4,352 cells/mm(2)). O. degus has a highly developed visual streak, and an area centralis located more temporally (peak density of 6,384 cells/mm(2)). The volumes of the contralateral GLd and superior colliculus (SC) are 15% larger in O. degus compared to O. lunatus. However, the ipsilateral projections to GLd and SC are 500% larger in O. lunatus than in O. degus. Other retinorecipient structures related to ocular movements and circadian activity showed no statistical differences between species. Our findings strongly suggest that nocturnal visual behavior leads to an enhancement of the structures associated with binocular vision, at least in the case of these rodents. Expansion of the binocular visual field in nocturnal species may have a beneficial effect in light and contrast sensitivity, but not necessarily in stereopsis. We discuss whether these conclusions can be extended to other mammalian and non-mammalian amniotes.

We isolated and characterized two human monoclonal antibodies to the envelope E2 protein of hepatitis C virus (HCV). Lymphoblastoid cell lines stably producing antibodies were obtained by immortalizing peripheral blood mononuclear cells of a patient with chronic hepatitis C using Epstein-Barr virus. Screening for antibody-positive clones was carried out by immunofluorescence with Huh7 cells expressing the E2 protein of HCV strain H (genotype 1a) isolated from the same patient. Isotype of resulting antibodies, #37 and #55, was IgG1/kappa and IgG1/lambda, respectively. Epitope mapping revealed that #37 and #55 recognize conformational epitopes spanning amino acids 429 to 652 and 508 to 607, respectively. By immunofluorescence using virus-infected Huh7.5 cells as targets both antibodies were reactive with all of the nine different HCV genotypes/subtypes tested. The antibodies showed a different pattern of immuno-staining; while #37 gave granular reactions mostly located in the periphery of the nucleus, #55 gave diffuse staining throughout the cytoplasm. Both antibodies were shown by immuno-gold electron microscopy to bind to intact viral particles. In a neutralization assay (focus-forming unit reduction using chimeric infectious HCV containing structural proteins derived from genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, 6a, and 7a), #55 inhibited the infection of all HCV genotypes tested but genotype 7a to a lesser extent. #37 did not neutralize any of these viruses. As a broadly cross-neutralizing human antibody, #55 may be useful for passive immunotherapy of HCV infection.

We present a new method for whole slide darkfield imaging. Whole Slide Imaging (WSI), also sometimes called virtual slide or virtual microscopy technology, produces images that simultaneously provide high resolution and a wide field of observation that can encompass the entire section, extending far beyond any single field of view. For example, a brain slice can be imaged so that both overall morphology and individual neuronal detail can be seen. We extended the capabilities of traditional whole slide systems and developed a prototype system for darkfield internal reflection illumination (DIRI). Our darkfield system uses an ultra-thin light-emitting diode (LED) light source to illuminate slide specimens from the edge of the slide. We used a new type of side illumination, a variation on the internal reflection method, to illuminate the specimen and create a darkfield image. This system has four main advantages over traditional darkfield: (1) no oil condenser is required for high resolution imaging (2) there is less scatter from dust and dirt on the slide specimen (3) there is less halo, providing a more natural darkfield contrast image, and (4) the motorized system produces darkfield, brightfield and fluorescence images. The WSI method sometimes allows us to image using fewer stains. For instance, diaminobenzidine (DAB) and fluorescent staining are helpful tools for observing protein localization and volume in tissues. However, these methods usually require counter-staining in order to visualize tissue structure, limiting the accuracy of localization of labeled cells within the complex multiple regions of typical neurohistological preparations. Darkfield imaging works on the basis of light scattering from refractive index mismatches in the sample. It is a label-free method of producing contrast in a sample. We propose that adapting darkfield imaging to WSI is very useful, particularly when researchers require additional structural information without the use of further staining.

Due to their beneficial reduction in morbidity and mortality angiotensin receptor blockers (ARBs) have become increasingly popular to treat hypertension. However, similar to angiotensin converting enzyme inhibitors, they can lead to severe hypotension in conjunction with general anesthesia and thus have been recommended to be withheld in the morning of surgery. Here, we present a 51 year old female who developed severe refractory hypotension after induction of general anesthesia, although she had discontinued her medication 24 hours preoperatively as instructed. Therefore, halting ARBs for more than 24 hours before surgery may be necessary. Heightened awareness of this potential interaction and recognizing the need to treat with vasopressin is required when ARB-induced hypotension occurs.

The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to the biological active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). Renal 1α-hydroxylase activity is the principal determinant of the circulating 1,25(OH)2D concentration and enzyme activity is tightly regulated by several factors. Fibroblast growth factor-23 (FGF-23) decreases serum 1,25(OH)2D concentrations by suppressing CYP27B1 mRNA abundance in mice. In extra-renal tissues, 1α-hydroxylase is responsible for local 1,25(OH)2D synthesis, which has important paracrine actions, but whether FGF-23 regulates CYP27B1 gene expression in extra-renal tissues is unknown. We sought to determine whether FGF-23 regulates CYP27B1 transcription in the kidney and whether extra-renal tissues are target sites for FGF-23-induced suppression of CYP27B1. In HEK293 cells transfected with the human CYP27B1 promoter, FGF-23 suppressed promoter activity by 70%, and the suppressive effect was blocked by CI-1040, a specific inhibitor of extracellular signal regulated kinase 1/2. To examine CYP27B1 transcriptional activity in vivo, we crossed fgf-23 null mice with mice bearing the CYP27B1 promoter-driven luciferase transgene (1α-Luc). In the kidney of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity was increased by 3-fold compared to that in wild-type/1α-Luc mice. Intraperitoneal injection of FGF-23 suppressed renal CYP27B1 promoter activity and protein expression by 26% and 60% respectively, and the suppressive effect was blocked by PD0325901, an ERK1/2 inhibitor. These findings provide evidence that FGF-23 suppresses CYP27B1 transcription in the kidney. Furthermore, we demonstrate that in FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA abundance are increased in several extra-renal sites. In the heart of FGF-23 null/1α-Luc mice, CYP27B1 promoter activity and mRNA were 2- and 5-fold higher, respectively, than in control mice. We also observed a 3- to 10-fold increase in CYP27B1 mRNA abundance in the lung, spleen, aorta and testis of FGF-23 null/1α-Luc mice. Thus, we have identified novel extra-renal target sites for FGF-23-mediated regulation of CYP27B1.

ABSTRACT The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.