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We assess the likelihood of moderate and severe psychological distress among Black immigrants. We test the region of context framework, which states that Black immigrants from majority-Black and racially mixed regions of origin have better health outcomes than Black immigrants from majority-white contexts. We utilize data from IPUMS Health Surveys, 2000–2018. We employed partial proportional odds models to assess the likelihood of moderate and severe psychological distress among Black immigrants and U.S.-born Black Americans. All immigrant groups, except for Black Europeans, are significantly less likely to be in moderate and severe distress vis-a-vis U.S.-born Black Americans (p

Subanesthetic dosing of intravenous ketamine has shown to be an effective treatment for patients with major depressive disorder. It is unknown whether sympathetic response is related to treatment outcomes. The purpose of this study is to evaluate sympathetic response to ketamine infusions as it relates to treatment outcomes.This retrospective study examines an outpatient population diagnosed with major depressive disorder or bipolar depression treated with ketamine infusions. Patient characteristics, depressive symptoms measured with the Patient Health Questionnaire (PHQ-9), and vital signs were retrieved by chart review. Patients (n = 145) were categorized as responders (50% reduction in PHQ-9 or less than 10 on final PHQ-9) or nonresponders. Changes in vital signs were recorded during each infusion for the initiation series.Ketamine responders (51.7%) showed a significant greater increase in systolic blood pressure response during the first infusion when compared with nonresponders. There was no difference seen in diastolic pressure, heart rate, or rate pressure product. Changes in vital signs for subsequent infusions also did not approach significance.Physiologic sensitivity to the effects of ketamine may predict treatment responsiveness. Blood pressure and heart rate did not always increase. Further work should examine possible influences on physiologic responses.

Flatt, AA, Esco, MR, Allen, JR, Robinson, JB, Bragg, A, Keith, CM, Fedewa, MV, and Earley, RL. Cardiac-autonomic responses to in-season training among Division-1 college football players. J Strength Cond Res 34(6): 1649-1656, 2020-Despite having to endure a rigorous in-season training schedule, research evaluating daily physiological recovery status markers among American football players is limited. The purpose of this study was to determine whether recovery of cardiac-autonomic activity to resting values occurs between consecutive-day, in-season training sessions among college football players. Subjects (n = 29) were divided into groups based on position: receivers and defensive backs (SKILL, n = 10); running backs, linebackers, and tight-ends (MID-SKILL, n = 11) and linemen (LINEMEN, n = 8). Resting heart rate (RHR) and the natural logarithm of the root mean square of successive differences multiplied by 20 (LnRMSSD) were acquired at rest in the seated position before Tuesday and Wednesday training sessions and repeated over 3 weeks during the first month of the competitive season. A position × time interaction was observed for LnRMSSD (p = 0.04), but not for the RHR (p = 0.33). No differences in LnRMSSD between days was observed for SKILL (Tuesday = 82.8 ± 9.3, Wednesday = 81.9 ± 8.7, p > 0.05). Small reductions in LnRMSSD were observed for MID-SKILL (Tuesday = 79.2 ± 9.4, Wednesday = 76.2 ± 9.5, p ≤ 0.05) and LINEMEN (Tuesday = 79.4 ± 10.5, Wednesday = 74.5 ± 11.5, p ≤ 0.05). The individually averaged changes in LnRMSSD from Tuesday to Wednesday were related to PlayerLoad (r = 0.46, p = 0.02) and body mass (r = -0.39, p = 0.04). Cardiac-parasympathetic activity did not return to resting values for LINEMEN or MID-SKILL before the next training session. Larger reductions in LnRMSSD tended to occur in players with greater body mass despite having performed lower workloads, although some individual variability was observed. These findings may have implications for how coaches and support staff address training and recovery interventions for players demonstrating inadequate cardiovascular recovery between sessions.

The caste system is a relatively rigid system of social hierarchy in India. The caste membership defines one’s access to resources and life opportunities. A growing body of research suggests that lower caste groups have an excess burden of morbidity and mortality in India. However, it is not clear as to what extent caste differences in health are conditioned by socioeconomic status (SES) indicators. This study examined the caste differences in hypertension and tested whether caste differences in hypertension are conditioned by education and household wealth in a representative sample of women in India. This study used data from the National Family Health Survey (NFHS) 2015–2016, India. The analysis is based on a nationally representative sample of 648,064 adult women aged 15–49 years. We used logistic regression to examine whether the association between caste and hypertension varied by education and wealth index using interactions and controlling for potential confounders. The regression models suggest that scheduled tribes and non-caste members have the highest odds of hypertension compared with privileged upper caste members. Interaction models indicate complex intersections of caste, education, and wealth index. The predicted probabilities derived from these interaction models suggest that while SES indicators are inversely associated with the odds of hypertension, the inverse patterning was significantly weaker in other backward classes and more protective in non-caste members compared with upper caste. Additionally, caste difference in predictive risk of hypertension tends to diverge at the lower levels of SES and become narrower at the higher levels of SES. These findings provide evidence of differential returns to SES and have implications for understanding the causes of SES patterning in health among disadvantaged caste groups in India.

Conservation across human-dominated landscapes requires an understanding of the social and ecological factors driving outcomes. Studies that link conservation outcomes to social and ecological factors have examined temporally static patterns. However, there may be different social and ecological processes driving increases and decreases in conservation outcomes that can only be revealed through temporal analyses. Through a case study of the invasion of Falcataria moluccana in Hawaii, we examined the association of social factors with increases and decreases in invader distributions over time and space. Over 7 years, rates of invader decrease varied substantially (66-100%) relative to social factors, such as building value, whether land was privately or publically owned, and primary residence by a homeowner, whereas rates of increase varied only slightly (0.1-3.6%) relative to such factors. These findings suggest that links between social factors and invasion in the study system may be driven more by landowners controlling existing invasive species, rather than by landowners preventing the spread of invasive species. We suggest that spatially explicit, time-dependent analyses provide a more nuanced understanding of the way social factors influence conservation outcomes. Such an understanding can help managers develop outreach programs and policies targeted at different types of landowners in human-dominated landscapes.Uso de un Análisis Espacialmente Explícito y Dependiente del Tiempo para Entender cómo Influyen los Factores Sociales sobre los Resultados de la Conservación Resumen La conservación dentro de los paisajes dominados por humanos requiere de un entendimiento de los factores sociales y ecológicos que afectan los resultados. Los estudios que conectan los resultados de la conservación con los factores sociales y ecológicos han examinado temporalmente los patrones estáticos. Sin embargo, puede haber diferentes procesos sociales y ecológicos que produzcan un incremento o una disminución en los resultados de la conservación, los cuales sólo pueden ser revelados por medio de los análisis temporales. Examinamos la asociación entre los factores sociales y el incremento y la disminución de la distribución de una invasión en el tiempo y el espacio con el estudio de caso de la invasión de Falcataria moluccana en Hawái. A lo largo de siete años las tasas de disminución de la invasión variaron considerablemente (66-100%) en relación con los factores sociales, como el valor de construcción, si la tierra era pública o privada, y si era la residencia principal del propietario, mientras que las tasas de incremento variaron solamente un poco (0.1-3.6%) en relación con dichos factores. Estos hallazgos sugieren que las conexiones entre los factores sociales y la invasión en el sistema de estudio podrían ser causados más por los propietarios que controlan a las especies invasoras existentes en lugar de ser causados por los propietarios que previenen la expansión de las especies invasoras. Sugerimos que los análisis espacialmente explícitos y dependientes del tiempo proporcionan un entendimiento más matizado de cómo los factores sociales influyen sobre los resultados de la conservación. Dicho entendimiento puede ayudar a los administradores a desarrollar programas y políticas de compromiso con la comunidad enfocadas en diferentes tipos de propietarios en los paisajes dominados por el humano.在人类主导的景观中开展保护需要了解社会和生态因素对保护成效的影响。目前, 将保护成效与社会和生态因素相结合的研究已经分析了当下的静态格局。然而, 可能存在一些不同的社会和生态过程推动或阻碍着保护, 它们的影响要通过时序分析才能得到揭示。我们通过对夏威夷入侵物种南洋楹 (Falcataria moluccana) 的案例分析, 检验了社会因素与入侵范围的时空变化之间的关系。结果表明, 在超过七年的时间里, 南洋楹减少的速率相对于社会因素 (如建筑价值、土地私有或公有、土地是否用作私有者的主要住宅) 变化很大 (66-100%) , 而增加速率相对于这些因素变化却很小 (0.1-3.6%) 。这些发现表明, 研究系统中社会因素与入侵的联系可能更多地受到土地所有者控制现有入侵物种的驱动, 而不是土地所有者防止入侵物种扩散的结果。我们认为, 基于时间的空间显式分析为研究社会因素如何影响保护成效提供了更精细的理解, 这有助于管理者在人类主导的景观中制定针对不同类型土地所有者的延伸项目和政策。【翻译: 胡怡思; 审校: 聂永刚】.

Flow-induced damage to red blood cells has been an issue of considerable importance since the introduction of the first cardiovascular devices. Early blood damage prediction models were based on measurements of damage by shear stress only. Subsequently, these models were extrapolated to include other components of the fluid stress tensor. However, the expanded models were not validated by measurements of damage in response to the added types of stress. Recent investigations have proposed that extensional stress might be more damaging to red cells than shear stress. In this study, experiments were conducted to compare human red cell deformation under laminar extensional stress versus laminar shear stress. It was found that the deformation caused by shear stress is matched by that produced by an extensional stress that is approximately 34 times smaller. Assuming that blood damage scales directly with cell deformation, this result indicates that mechanistic blood damage prediction models should weigh extensional stress more than shear stress.

Background: As an alternative to advection, solute transport by shear-augmented dispersion within oscillatory cerebrospinal fluid flow was investigated in small channels representing the basement membranes located between cerebral arterial smooth muscle cells, the paraarterial space surrounding the vessel wall and in large channels modeling the spinal subarachnoid space (SSS).Methods: Geometries were modeled as two-dimensional. Fully developed flows in the channels were modeled by the Darcy-Brinkman momentum equation and dispersion by the passive transport equation. Scaling of the enhancement of axial dispersion relative to molecular diffusion was developed for regimes of flow including quasi-steady, porous and unsteady, and for regimes of dispersion including diffusive and unsteady.Results: Maximum enhancement occurs when the characteristic time for lateral dispersion is matched to the cycle period. The Darcy-Brinkman model represents the porous media as a continuous flow resistance, and also imposes no-slip boundary conditions at the walls of the channel. Consequently, predicted dispersion is always reduced relative to that of a channel without porous media, except when the flow and dispersion are both unsteady.Discussion/conclusions: In the basement membranes, flow and dispersion are both quasi-steady and enhancement of dispersion is small even if lateral dispersion is reduced by the porous media to achieve maximum enhancement. In the paraarterial space, maximum enhancement R max = 73,200 has the potential to be significant. In the SSS, the dispersion is unsteady and the flow is in the transition zone between porous and unsteady. Enhancement is 5.8 times that of molecular diffusion, and grows to a maximum of 1.6E+6 when lateral dispersion is increased. The maximum enhancement produces rostral transport time in agreement with experiments.

Two limitations have been discovered in the derivation of the Eulerian method of hemolysis prediction using a linearized blood damage function. First is that in the transformation from the Lagrangian material volume of the original power-law model to a fixed Eulerian control volume, the spatial dependence of duration of exposure to fluid stress was neglected. This omission has the implication that the Eulerian method as reported is valid only for steady, uniaxial flow in which velocity is constant along streamlines. The second issue is related to linearization, which involves distributing an exponent across an integral. This operation is valid only for limited conditions that include the exponent being unity (which is not the case for any power-law hemolysis models) or the blood damage function being constant throughout the flow regime. These constraints severely restrict the applicability of the Eulerian method. An example problem is presented that demonstrates that the source term of the Eulerian method as reported does not account for differences in velocity between 2 similar flows. Correcting the source term to match the hemolysis prediction to that of the original, unlinearized method requires an analytical description of the flow field that may not be easily obtained for the complex flows in some cardiovascular devices.

Brain function relies on a precisely coordinated and dynamic balance between the functional integration and segregation of distinct networks. Characterizing the way in which brain regions reconfigure their interactions to give rise to distinct but hidden brain states remains an open challenge. In this paper, we propose a Bayesian method for characterizing community structure-based latent brain states and showcase a novel strategy based on posterior predictive discrepancy using the latent block model to detect transitions between community structures in blood oxygen level-dependent (BOLD) time series. The set of estimated parameters in the model includes a latent label vector that assigns network nodes to communities, and also block model parameters that reflect the weighted connectivity within and between communities. Besides extensive in-silico model evaluation, we also provide empirical validation (and replication) using the Human Connectome Project (HCP) dataset of 100 healthy adults. Our results obtained through an analysis of task-fMRI data during working memory performance show appropriate lags between external task demands and change-points between brain states, with distinctive community patterns distinguishing fixation, low-demand and high-demand task conditions.

Nursing homes and other long term-care facilities account for a disproportionate share of COVID-19 cases and fatalities worldwide. Outbreaks in U.S. nursing homes have persisted despite nationwide visitor restrictions beginning in mid-March. An early report issued by the Centers for Disease Control and Prevention identified staff members working in multiple nursing homes as a likely source of spread from the Life Care Center in Kirkland, Washington to other skilled nursing facilities. The full extent of staff connections between nursing homes---and the crucial role these connections serve in spreading a highly contagious respiratory infection---is currently unknown given the lack of centralized data on cross-facility nursing home employment. In this paper, we perform the first large-scale analysis of nursing home connections via shared staff using device-level geolocation data from 30 million smartphones, and find that 7 percent of smartphones appearing in a nursing home also appeared in at least one other facility---even after visitor restrictions were imposed. We construct network measures of nursing home connectedness and estimate that nursing homes have, on average, connections with 15 other facilities. Controlling for demographic and other factors, a home's staff-network connections and its centrality within the greater network strongly predict COVID-19 cases. Traditional federal regulatory metrics of nursing home quality are unimportant in predicting outbreaks, consistent with recent research. Results suggest that eliminating staff linkages between nursing homes could reduce COVID-19 infections in nursing homes by 44 percent., Comment: 22 pages, 2 figures. This working paper updated July 22nd, 2020. For the most recent version, see https://www.anderson.ucla.edu/faculty_pages/keith.chen/papers/WP_Nursing_Home_Networks_and_COVID19.pdf

Purpose: To track cardiac-autonomic functioning, indexed by heart-rate variability, in American college football players throughout a competitive period. Methods: Resting heart rate (RHR) and the natural logarithm root mean square of successive differences (LnRMSSD) were obtained throughout preseason and ∼3 times weekly leading up to the national championship among 8 linemen and 12 nonlinemen. Seated 1-minute recordings were performed via mobile device and standardized for time of day and proximity to training. Results: Relative to preseason, linemen exhibited suppressed LnRMSSD during camp-style preparation for the playoffs (P = .041, effect size [ES] = −1.01), the week of the national semifinal (P P = .005, ES = −1.16). As a combined group, increases in RHR (P R2 = .02–.77) while LnRMSSD trended downward (negative slopes, R2 = .02–.62) throughout the season. Preseason to postseason changes in RHR (r = .50, P = .025) and LnRMSSD (r = −.68, P Conclusions: Heart-rate variability tracking revealed progressive autonomic imbalance in the lineman position group, with individual players showing suppressed values by midseason. Attenuated parasympathetic activation is a hallmark of impaired recovery and may contribute to cardiovascular maladaptations reported to occur in linemen following a competitive season. Thus, a descending pattern may serve as an easily identifiable red flag requiring attention from performance and medical staff.

Following conservative media skepticism of hurricane warnings in 2017, a partisan wedge in evacuation behavior rapidly emerged., Mistrust of scientific evidence and government-issued guidelines is increasingly correlated with political affiliation. Survey evidence has documented skepticism in a diverse set of issues including climate change, vaccine hesitancy, and, most recently, COVID-19 risks. Less well understood is whether these beliefs alter high-stakes behavior. Combining GPS data for 2.7 million smartphone users in Florida and Texas with 2016 U.S. presidential election precinct-level results, we examine how conservative-media dismissals of hurricane advisories in 2017 influenced evacuation decisions. Likely Trump-voting Florida residents were 10 to 11 percentage points less likely to evacuate Hurricane Irma than Clinton voters (34% versus 45%), a gap not present in prior hurricanes. Results are robust to fine-grain geographic controls, which compare likely Clinton and Trump voters living within 150 m of each other. The rapid surge in media-led suspicion of hurricane forecasts—and the resulting divide in self-protective measures—illustrates a large behavioral consequence of science denialism.

A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Several compounds equipotent against both species were identified and profiled in vivo.

Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models' usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model's parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.

Background Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain. Methods A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial–temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial–temporal tracer concentration over 24-h. Results After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial–temporal tracer concentration under Neurapheresis therapy (R2 = 0.89 with + 2.13% and − 1.93% tracer concentration confidence interval). Conclusion A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.

Light pollution is one of the most rapidly increasing types of environmental degradation. Its levels have been growing exponentially over the natural nocturnal lighting levels provided by starlight and moonlight. To limit this pollution several effective practices have been defined: the use of shielding on lighting fixture to prevent direct upward light, particularly at low angles above the horizon; no over lighting, i.e. avoid using higher lighting levels than strictly needed for the task, constraining illumination to the area where it is needed and the time it will be used. Nevertheless, even after the best control of the light distribution is reached and when the proper quantity of light is used, some upward light emission remains, due to reflections from the lit surfaces and atmospheric scatter. The environmental impact of this "residual light pollution", cannot be neglected and should be limited too. Here we propose a new way to limit the effects of this residual light pollution on wildlife, human health and stellar visibility. We performed analysis of the spectra of common types of lamps for external use, including the new LEDs. We evaluated their emissions relative to the spectral response functions of human eye photoreceptors, in the photopic, scotopic and the 'meltopic' melatonin suppressing bands. We found that the amount of pollution is strongly dependent on the spectral characteristics of the lamps, with the more environ- mentally friendly lamps being low pressure sodium, followed by high pressure sodium. Most polluting are the lamps with a strong blue emission, like Metal Halide and white LEDs. Migration from the now widely used sodium lamps to white lamps (MH and LEDs) would produce an increase of pollution in the scotopic and melatonin suppression bands of more than five times the present levels, supposing the same photopic installed flux. This increase will exacerbate known and possible unknown effects of light pollution on human health, environment and on visual perception of the Universe by humans. We present quantitative criteria to evaluate the lamps based on their spectral emissions and we suggest regulatory limits for future lighting.

Anxiety and sensory symptoms are highly prevalent and meaningful in the daily lives of individuals with autism spectrum disorder (ASD). Despite the importance of carefully measuring, researching, and treating these symptoms, current methods in ASD seldom include self-report. This study investigated the consistency of adolescent and parent reports of anxiety and auditory sensitivity in individuals with ASD, and examined their validity via comparisons with sympathetic arousal at baseline and in response to an auditory challenge. Fifty adolescent-parent dyads (n = 26 ASD, n = 24 typically developing; 12–16 years old; IQ>80) completed parallel versions of both anxiety and auditory hypersensitivity scales, which were compared to heart rate collected at rest and during an aversive noise task. Adolescents with ASD exhibited greater anxiety and auditory hypersensitivity than their peers, based on both self and parent report. Across groups, self-report was higher than parent report. In individuals with ASD, a significant relationship was found between self-reported anxiety and autonomic arousal at rest, and between self-reported auditory sensitivity and autonomic reactivity during the noise task. These relationships were not significant for parent-report. These findings extend past work by demonstrating greater self-reported (than parent-reported) anxiety and sensory symptoms. Furthermore, the presence of significant correlations between self-reported symptoms and sympathetic arousal supports the validity of self-report in adolescents with ASD with average or above average cognitive abilities. This indicates that adolescents with ASD have a unique perspective on their internal experience, which can complement parent reports and provide a more comprehensive assessment of symptoms in research and clinical settings.

Background Much of the extensive research regarding transmission of malaria is underpinned by mathematical modelling. Compartmental models, which focus on interactions and transitions between population strata, have been a mainstay of such modelling for more than a century. However, modellers are increasingly adopting agent-based approaches, which model hosts, vectors and/or their interactions on an individual level. One reason for the increasing popularity of such models is their potential to provide enhanced realism by allowing system-level behaviours to emerge as a consequence of accumulated individual-level interactions, as occurs in real populations. Methods A systematic review of 90 articles published between 1998 and May 2018 was performed, characterizing agent-based models (ABMs) relevant to malaria transmission. The review provides an overview of approaches used to date, determines the advantages of these approaches, and proposes ideas for progressing the field. Results The rationale for ABM use over other modelling approaches centres around three points: the need to accurately represent increased stochasticity in low-transmission settings; the benefits of high-resolution spatial simulations; and heterogeneities in drug and vaccine efficacies due to individual patient characteristics. The success of these approaches provides avenues for further exploration of agent-based techniques for modelling malaria transmission. Potential extensions include varying elimination strategies across spatial landscapes, extending the size of spatial models, incorporating human movement dynamics, and developing increasingly comprehensive parameter estimation and optimization techniques. Conclusion Collectively, the literature covers an extensive array of topics, including the full spectrum of transmission and intervention regimes. Bringing these elements together under a common framework may enhance knowledge of, and guide policies towards, malaria elimination. However, because of the diversity of available models, endorsing a standardized approach to ABM implementation may not be possible. Instead it is recommended that model frameworks be contextually appropriate and sufficiently described. One key recommendation is to develop enhanced parameter estimation and optimization techniques. Extensions of current techniques will provide the robust results required to enhance current elimination efforts. Electronic supplementary material The online version of this article (10.1186/s12936-018-2442-y) contains supplementary material, which is available to authorized users.

This study examined the impact of noise on cognitive performance in autism spectrum disorder (ASD), while concurrently measuring sympathetic responses. Adolescents with and without ASD completed visually presented span tasks in a 2 × 2 experimental manipulation of noise (quiet vs. 75 dB gated broadband noise) and task difficulty (easier vs. harder). Analyses revealed a significant noise × difficulty interaction on performance, and a significant group × noise × difficulty interaction on sympathetic arousal. Correlational analyses indicated an adaptive effect of noise and increased arousal on performance in the easier condition for the control group and a detrimental effect of noise and increased arousal in the harder condition for the ASD group. Implications for sensory processing research and intervention development are discussed.

Background Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow–Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels. The second hypothesis involves flow of interstitial fluid from the parenchyma to lymphatic vessels along basement membranes between arterial smooth muscle cells. Methods This article evaluates the plausibility of steady, pressure-driven flow in these channels with one-dimensional branching models. Results According to the models, the hydraulic resistance of arterial basement membranes is too large to accommodate estimated interstitial perfusion of the brain, unless the flow empties to lymphatic ducts after only several generations (still within the parenchyma). The estimated pressure drops required to drive paraarterial and paravenous flows of the same magnitude are not large, but paravenous flow back to the CSF space means that the total pressure difference driving both flows is limited to local pressure differences among the different CSF compartments, which are estimated to be small. Conclusions Periarterial flow and glymphatic circulation driven by steady pressure are both found to be implausible, given current estimates of anatomical and fluid dynamic parameters.

OBJECTIVES: Black Caribbeans in the United States have been the victims of major discrimination (e.g., unfairly fired, denied a promotion, denied housing). What is not known is the degree to which they also experience more routine forms of everyday discrimination such as receiving poor restaurant service, being perceived as dishonest, and being followed in stores. This paper investigates the distribution and correlates of everyday discrimination among a national sample of black Caribbeans in the U.S. DESIGN: This analysis used the black Caribbean sub-sample (n=1,621) of the National Survey of American Life. Demographic and immigration status correlates of ten items from the Everyday Discrimination Scale were investigated: being treated with less courtesy, treated with less respect, receiving poor restaurant service, being perceived as not smart, being perceived as dishonest, being perceived as not as good as others, and being feared, insulted, harassed, or followed in stores. RESULTS: Roughly one out of ten black Caribbeans reported that, on a weekly basis, they were treated with less courtesy and other people acted as if they were better than them, were afraid of them, and as if they were not as smart. Everyday discrimination was more frequent for black Caribbeans who were male, never married, divorced/separated, earned higher incomes, and who were second or third generation immigrants. Black Caribbeans attributed the majority of the discrimination they experienced to their race. CONCLUSION: To our knowledge, this is the first study to provide an in-depth investigation of everyday discrimination among the black Caribbean population. It provides the frequency, types and correlates of everyday discrimination reported by black Caribbeans in the United States. Understanding the frequency and types of discrimination is important because of the documented negative impacts of everyday discrimination on physical and mental health.

OBJECTIVES This study evaluated the effectiveness of the Center for Executive Medicine (CEM) concierge primary care practice on preventive colorectal cancer (CRC) screening rates relative to local and national comparator data. METHODS We performed an electronic medical record search encompassing our entire patient population who are between the ages of 50 and 75 years to determine the rate of CRC screening. We compared this rate with the average rate of Medicare Advantage plans reported by our Independent Physician Association (IPA) in 2015 and national health plans reported by the National Committee for Quality Assurance in 2014. RESULTS The CEM had a CRC screening rate of 90.2%, which was significantly higher than local IPA Medicare Advantage plans (63.3%) and National Committee for Quality Assurance national plans (57.7%-66.5%). CEM members were significantly more likely than were IPA members to undergo screening (odds ratio 1.425, 95% confidence interval 1.348-1.507, P < 0.0001). CONCLUSIONS These results suggest that the CEM practice strategy and processes increase CRC screening rates.

AIM: Using a nationally representative sample of African American men, this study investigated the associations between lifetime history of incarceration, discrimination, and mental health (e.g. depressive symptoms and psychological distress). We hypothesized that discrimination would fully mediate the association between incarceration history and mental health outcomes among African American men. METHODS: Using a cross-sectional design, our analysis included 1,271 African American men who participated in the National Survey of American Life (NSAL), 2001–2003. Incarceration history was the main independent variable. Depressive symptoms and psychological distress were the dependent variables. Everyday discrimination was the mediator. Age, education, and income were covariates. Structural equation models (SEM) were used for data analysis. RESULTS: Among African American men, incarceration history was positively associated with perceived discrimination, depressive symptoms, and psychological distress. Everyday discrimination fully mediated the associations between incarceration history and both depressive symptoms and psychological distress. CONCLUSION: Discrimination may play an important role in the mental health problems of African American men with a history of incarceration. These findings have public policy implications as well as clinical implications for mental health promotion of African American men. Policies that reduce preventable incarceration or at least reduce subsequent discrimination for those who have been incarcerated may enhance mental health of previously incarcerated African American men.

Evidence is accumulating that blood flow patterns in the cardiovascular system and in cardiovascular devices do, in some instances, depend on blood viscoelasticity. Thus, to better understand the challenges to providing circulatory support and surgical therapies for pediatric and adult patients, viscous and elastic components of complex blood viscoelasticity of 31 pediatric patients were compared to those of 29 adult patients with a Vilastic-3 rheometer. A random effects model with categorical age covariates found statistically significant differences between pediatric and adult patients for log viscosity (p = 0.005). Log strain (p

African American female students' elevated suspension risk has received national attention. Despite a number of studies documenting racial/ethnic disparities in African American females' school suspension risk, few investigations have attempted to explain why these disparities occur. The purpose of this study was to examine the role of colorism in explaining suspension risk using a nationally representative sample of adolescent females. Controlling for individual- and school-level characteristics associated with school discipline such as student-teacher relationships, prior discipline history, school size and type, the results indicate that colorism was a significant predictor of school suspension risk. African American female adolescents with darker complexions were almost twice as likely to receive an out-of-school suspension as their White female peers. This finding was not found for African American female students with lighter skin complexions. Implications for adopting a colorist framework for understanding school discipline outcomes and future research for advancing the field in this area are discussed. (PsycINFO Database Record

Tracers infused into the brain appear to be transported along channels surrounding cerebral blood vessels. Bulk fluid flow has been hypothesized in paravascular "glymphatic" channels (outer space between the pial membrane and astrocyte endfeet), as well as in the periarterial space (inner space between smooth muscle cells). The plausibility of net flow in these channels due to steady and oscillatory pressures is reviewed, as is that of transport by oscillatory shear-enhanced dispersion in the absence of net flow. Models including 1D branching networks of annular channels and an expanded compartmental model for humans both predict that flow driven by physiologic steady pressure differences is unlikely in both periarterial and paraarterial spaces, whether the spaces are open or filled with porous media. One exception is that a small additional steady pressure difference could drive paraarterial flow if the space is open. The potential that the tracer injection itself could present such a pressure difference is outlined. Oscillatory (peristaltic) wall motion alone has been found to be insufficient to drive significant forward flow. However, a number of hypothesized mechanisms that have yet to be experimentally verified in the brain may create directional flow in combination with wall motion. Shear-augmented dispersion due to oscillatory pressure in channels with a range of porosity has been modeled analytically. Enhancement of axial dispersion is small for periarterial channels. In open paraarterial channels, dispersion enhancement with optimal lateral mixing is large enough that it may explain observed tracer transport without net forward fluid flow.

Wilkerson, GB, Gupta, A, Allen, JR, Keith, CM, and Colston, MA. Utilization of practice session average inertial load to quantify college football injury risk. J Strength Cond Res 30(9): 2369-2374, 2016-Relatively few studies have investigated the potential injury prevention value of data derived from recently developed wearable technology for measurement of body mass accelerations during the performance of sport-related activities. The available evidence has been derived from studies focused on avoidance of overtraining syndrome, which is believed to induce a chronically fatigued state that can be identified through monitoring of inertial load accumulation. Reduced variability in movement patterns is also believed to be an important injury risk factor, but no evidence currently exists to guide interpretation of data derived from inertial measurement units (IMUs) in this regard. We retrospectively analyzed archived data for a cohort of 45 National Collegiate Athletic Association Division 1-football bowl subdivision football players who wore IMUs on the upper back during practice sessions to quantify any associations between average inertial load measured during practice sessions and occurrence of musculoskeletal sprains and strains. Both the coefficient of variation for average inertial load and frequent exposure to game conditions were found to be strongly associated with injury occurrence. Having either or both of the 2 risk factors provided strong discrimination between injured and noninjured players (χ = 9.048; p = 0.004; odds ratio = 8.04; 90% CI: 2.39, 27.03). Our findings may facilitate identification of individual football players who are likely to derive the greatest benefit from training activities designed to reduce injury risk through improved adaptability to rapidly changing environmental demands.

Studies evaluating the immunogenicity of two pediatric tick-borne encephalitis virus (TBEV) vaccines have reported contradictory results. These vaccines are based on two different strains of the European TBEV subtype: FSME-Immun Junior is based on the Neudörfl (Nd) strain, whereas Encepur Children is based on the Karlsruhe (K23) strain. The antibody (Ab) response induced by these two vaccines might be influenced by antigenic differences in the envelope (E) protein, which is the major target of neutralizing antibodies. We used an established hybrid virus assay platform to compare the levels of induction of neutralizing antibodies against the two vaccine virus strains in children aged 1 to 11 years who received two immunizations with FSME-Immun Junior or Encepur Children. The influence of amino acid differences between the E proteins of the Nd and K23 vaccine strains was investigated by mutational analyses and three-dimensional computer modeling. FSME-Immun Junior induced 100% seropositivity and similar neutralizing antibody titers against hybrid viruses containing the TBEV E protein of the two vaccine strains. Encepur Children induced 100% seropositivity only against the hybrid virus containing the E protein of the homologous K23 vaccine strain. Antibody responses induced by Encepur Children to the hybrid virus containing the E protein of the heterologous Nd strain were substantially and significantly ( P < 0.001) lower than those to the K23 vaccine strain hybrid virus. Structure-based mutational analyses of the TBEV E protein indicated that this is due to a mutation in the DI-DII hinge region of the K23 vaccine strain E protein which may have occurred during production of the vaccine seed virus and which is not present in any wild-type TBE viruses. IMPORTANCE Our data suggest that there are major differences in the abilities of two European subtype pediatric TBEV vaccines to induce antibodies capable of neutralizing heterologous TBEV strains. This is a result of a mutation in the DI-DII hinge region of the E protein of the K23 vaccine virus strain used to manufacture Encepur Children which is not present in the Nd strain used to manufacture FSME-Immun Junior or in any other known naturally occurring TBEVs.

Leukotrienes (LTs) and related species are proinflammatory lipid mediators derived from arachidonic acid (AA) that have pathological roles in autoimmune and inflammatory conditions, cardiovascular diseases, and cancer. 5-Lipoxygenase activating protein (FLAP) plays a critical accessory role in the conversion of AA to LTA4, and its subsequent conversion to LTC4 by LTC4 synthase. Pharmacological inhibition of FLAP results in a loss of LT production by preventing the biosynthesis of both LTB4 and LTC4, making it an attractive target for the treatment of inflammatory diseases in which LTs likely play a role. Small-molecule (SM) drugs often exhibit polypharmacology through various pathways, which may explain the differential therapeutic efficacies of compounds sharing structural similarity. We have profiled a series of SM FLAP modulators for their selectivity across enzymes of AA cascade in human whole blood (HWB), using a recently developed LC/MS (liquid chromatography-mass spectrometry)-based high-throughput lipidomics platform that monitors 122 eicosanoids in multiplex. Highly efficient data acquisition coupled with fast and accurate data analysis allowed facile compound profiling from ex vivo study samples. This platform allowed us to quantitatively map the effects of those SMs on the entire AA cascade, demonstrating its potential to discriminate structurally related compounds.

We examined how sociopolitical context (marked by generational cohort) and maternal skin color interacted to influence preterm delivery (PTD) rates in sample of Black women. Data were from 1410 Black women, ages 18–45 years, residing in Metropolitan Detroit, MI enrolled (2009–2011) in the Life-course Influences on Fetal Environments (LIFE) Study. Because we hypothesized that generational differences marked by changes in the sociopolitical context would influence exposure to racism, we categorized women into two cohorts by maternal birth year: a) Generation X, 1964–1983 and b) Millennial, 1984–1993. Descriptive results showed similar PTD rates by generational cohort, Generation X: 16.3% vs. Millennials: 16.1%. Yet, within each generation, PTD rates varied by women's skin tone (categorized: light, medium, and dark brown). Poisson regression models confirmed a significant interaction between generational cohort and maternal skin tone predicting PTD (P = 0.001); suggesting a salubrious association between light brown skin tone (compared to medium and dark) and PTD for Generation X. However, Millennials with medium and dark brown skin experienced lower PTD rates than their light Millennial counterparts. Research should consider sociopolitical context and the salience of skin tone bias when investigating racial health disparities, including those in perinatal health.

ObjectiveCHA2DS2-VASc is a stroke risk classification system developed to improve the precision of stroke risk classification. The current study examined the validity of CHA2DS2-VASc in a sample of healthy older adults using executive function measures of processing speed, working memory, and cognitive flexibility that are sensitive to cerebrovascular risk factors.MethodsParticipants included 51 community-dwelling, healthy older adults (ages 53–86) recruited from both the community and cardiology clinics. CHA2DS2-VASc was utilized as a measure of stroke risk. Measures of executive functioning and processing speed included the Paced Auditory Serial Addition Test (PASAT), Delis–Kaplan Executive Function System (DKEFS) Number–Letter Switching, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding.ResultsCHA2DS2-VASc scores significantly predicted scores on the PASAT, DKEFS Number-Letter Switching, and RBANS Coding, such that greater stroke risk was associated with poorer performances on tests of executive functioning and processing speed. These relationships were observed over and above the potential influence of educational attainment and symptoms of depression.ConclusionSignificant relations between stroke risk classification and performance on several measures of executive functioning provide support for a wider and more generalized use of CHA2DS2-VASc with healthy older adults. These findings further highlight the importance of early identification and treatment of stroke risk factors associated with cognitive decline. Findings suggest that CHA2DS2-VASc is a practical and useful tool for patients and their providers in the early detection of stroke risk and development of individualized treatment plans.

Time series segmentation aims to identify segment boundary points in a time series, and to determine the dynamical properties corresponding to each segment. To segment time series data, this article presents a Bayesian change-point model in which the data within segments follows an autoregressive moving average (ARMA) model. A prior distribution is defined for the number of change-points, their positions, segment means and error terms. To quantify uncertainty about the location of change-points, the resulting posterior probability distributions are sampled using the Generalized Gibbs sampler Markov chain Monte Carlo technique. This methodology is illustrated by applying it to simulated data and to real data known as the well-log time series data. This well-log data records the measurements of nuclear magnetic response of underground rocks during the drilling of a well. Our approach has high sensitivity, and detects a larger number of change-points than have been identified by comparable methods in the existing literature.

Introduction Literature posits that discrimination can be a barrier to racial and ethnic minorities’ healthcare use. This study examines the relationship between perceived discrimination in the form of racial microaggressions and delayed prenatal care in African American women. It also investigates whether this relationship is modified by women's shade of skin color owing to societal attitudes and beliefs tied to colorism (also known as skin-tone bias). Methods Data were collected from a cohort of 1,410 black, African American women in metropolitan Detroit, Michigan, enrolled in 2009–2011 (analyzed between August 2017 and July 2018). Perceived racial microaggressions were assessed using the 20-item Daily Life Experiences of Racism and Bother scale. Logistic regression modeled the relationship between the Daily Life Experiences of Racism and Bother scale and delayed prenatal care, defined as third trimester or no prenatal care entry. Results Nearly a quarter (24.8%) of women had delayed prenatal care. Logistic regression models showed that a Daily Life Experiences of Racism and Bother score above the median was associated with delayed prenatal care (AOR=1.31, 95% CI=1.00, 1.71). This association was moderated by self-reported maternal skin tone (interaction p=0.03). A higher Daily Life Experiences of Racism and Bother score was associated with delayed prenatal care among African-American women at either end of the color continuum (light brown: AOR=1.64, 95% CI=1.02, 2.65; dark brown: AOR=2.30, 95% CI=1.20, 4.41) but not in the middle (medium brown women). Conclusions Skin tone–based mistreatment in tandem with racial discrimination in the form of racial microaggressions may influence African American women's use of prenatal care. These findings have implications related to the engagement of women of color, particularly African American women, in healthcare systems and maternal and child health programs.

Cerebrospinal fluid (CSF) dynamics are thought to play a vital role in central nervous system (CNS) physiology. The objective of this study was to investigate the impact of spinal cord (SC) nerve roots (NR) on CSF dynamics. A subject-specific computational fluid dynamics (CFD) model of the complete spinal subarachnoid space (SSS) with and without anatomically realistic NR and nonuniform moving dura wall deformation was constructed. This CFD model allowed detailed investigation of the impact of NR on CSF velocities that is not possible in vivo using magnetic resonance imaging (MRI) or other noninvasive imaging methods. Results showed that NR altered CSF dynamics in terms of velocity field, steady-streaming, and vortical structures. Vortices occurred in the cervical spine around NR during CSF flow reversal. The magnitude of steady-streaming CSF flow increased with NR, in particular within the cervical spine. This increase was located axially upstream and downstream of NR due to the interface of adjacent vortices that formed around NR.

OBJECTIVE: This paper examines how mortality covaries with observed skin tone among blacks and in relation to whites. Additionally, the study analyzes the extent to which social factors such as socioeconomic status affect this relationship. DESIGN: This study uses data from the 1982 General Social Survey (N = 1,689) data linked to the National Death Index until 2008. We use this data to examine the links between race, observed skin tone among blacks, and all-cause mortality. Piecewise exponential hazard modeling was used to estimate disparities in skin tone mortality among blacks, and relative to whites. The multivariate models control for age, education, gender, region, metropolitan statistical area, marital status, labor force status, and household income. RESULTS: Observed skin tone is a significant determinant of mortality among blacks and in relation to whites. Light skinned blacks had the lowest mortality hazards among blacks, while respondents with medium and dark brown skin experienced significantly higher mortality. The observed skin tone mortality disparities covaried with education; there are significant mortality disparities across observed skin tone groups among black respondents with high school or more education, and nonsignificant disparities among those with less education. CONCLUSION: It is crucial to identify the social processes driving racial disparities in health and mortality. The findings reveal that the nuanced social experiences of blacks with different observed skin tones markedly change the experience of racial inequality. Research on the nuanced social processes and biological mechanisms that connect differences in observed skin tone to mortality outcomes promises to better illuminate the experience of racial inequality and policy mechanisms we can use to undermine it.

Rationale Research assessing the health-related consequences of perceived discrimination depends upon high quality measures of perceived discrimination. The Everyday Discrimination Scale (EDS) is among the most frequently used instruments to assess perceptions of discrimination in general, as well as specific types of discrimination (e.g., based on race/ethnicity or age). While numerous studies attest to its validity and reliability for racial/ethnic minority groups, no existing study has examined its psychometric equivalence across gender, age, or socio-economic groups. This study fills this gap. Hypothesis We hypothesize that because social hierarchies of race/ethnicity, age, gender and class have different histories and are differently organized and institutionalized in contemporary United States, racial/ethnic, age, gender, and education-based groups differ in the types of discrimination they experience and perceive. As a result, the EDS may not be equivalent across these social groups. Method We test this hypothesis by analyzing data from the 2015 US Texas Diversity Study (N=1,049), a telephone survey of English- and Spanish-speaking adults. We examine two forms of the EDS – one focusing on discrimination regardless of attribution and one focusing specifically on discrimination attributed to respondents’ race/ethnicity. Results Multi-group confirmatory factor analyses revealed that neither version of the scale generates estimates of discrimination that can be meaningfully compared across all racial/ethnic, age, gender, and education-based groups. Conclusions Our results urge caution when drawing comparisons of perceived discrimination across diverse social groups based on the EDS and point to avenues for future scale development.

Research on growing American political polarization and antipathy primarily studies public institutions and political processes, ignoring private effects, including strained family ties. Using anonymized smartphone-location data and precinct-level voting, we show that Thanksgiving dinners attended by residents from opposing-party precincts were 30 to 50 minutes shorter than same-party dinners. This decline from a mean of 257 minutes survives extensive spatial and demographic controls. Reductions in the duration of Thanksgiving dinner in 2016 tripled for travelers from media markets with heavy political advertising-an effect not observed in 2015-implying a relationship to election-related behavior. Effects appear asymmetric: Although fewer Democratic-precinct residents traveled in 2016 than in 2015, Republican-precinct residents shortened their Thanksgiving dinners by more minutes in response to political differences. Nationwide, 34 million hours of cross-partisan Thanksgiving dinner discourse were lost in 2016 owing to partisan effects.

Flatt, AA, Esco, MR, Allen, JR, Robinson, JB, Earley, RL, Fedewa, MV, Bragg, A, Keith, CM, and Wingo, JE. Heart rate variability and training load among National Collegiate Athletic Association Division 1 college football players throughout spring camp. J Strength Cond Res 32(11): 3127-3134, 2018-The purpose of this study was to determine whether recovery of cardiac-autonomic activity to baseline occurs between consecutive-day training sessions among positional groups of a collegiate football team during Spring camp. A secondary aim was to evaluate relationships between chronic (i.e., 4-week) heart rate variability (HRV) and training load parameters. Baseline HRV (lnRMSSD_BL) was compared with HRV after ∼20 hours of recovery before next-day training (lnRMSSDpost20) among positional groups composed of SKILL (n = 11), MID-SKILL (n = 9), and LINEMEN (n = 5) with a linear mixed model and effect sizes (ES). Pearson and partial correlations were used to quantify relationships between chronic mean and coefficient of variation (CV) of lnRMSSD (lnRMSSD_chronic and lnRMSSDcv, respectively) with the mean and CV of PlayerLoad (PL_chronic and PL_cv, respectively). A position × time interaction was observed for lnRMSSD (p = 0.01). lnRMSSD_BL was higher than lnRMSSDpost20 for LINEMEN (p0.01; ES = large), whereas differences for SKILL and MID-SKILL were not statistically different (p0.05). Players with greater body mass experienced larger reductions in lnRMSSD (r = -0.62, p0.01). Longitudinally, lnRMSSDcv was significantly related to body mass (r = 0.48) and PL_chronic (r = -0.60). After adjusting for body mass, lnRMSSDcv and PL_chronic remained significantly related (r = -0.43). The ∼20-hour recovery time between training sessions on consecutive days may not be adequate for restoration of cardiac-parasympathetic activity to baseline among LINEMEN. Players with a lower chronic training load throughout camp experienced greater fluctuation in lnRMSSD (i.e., lnRMSSDcv) and vice versa. Thus, a capacity for greater chronic workloads may be protective against perturbations in cardiac-autonomic homeostasis among American college football players.

Background Computational identification of non-coding RNAs (ncRNAs) is a challenging problem. We describe a genome-wide analysis using Bayesian segmentation to identify intronic elements highly conserved between three evolutionarily distant vertebrate species: human, mouse and zebrafish. We investigate the extent to which these elements include ncRNAs (or conserved domains of ncRNAs) and regulatory sequences. Results We identified 655 deeply conserved intronic sequences in a genome-wide analysis. We also performed a pathway-focussed analysis on genes involved in muscle development, detecting 27 intronic elements, of which 22 were not detected in the genome-wide analysis. At least 87% of the genome-wide and 70% of the pathway-focussed elements have existing annotations indicative of conserved RNA secondary structure. The expression of 26 of the pathway-focused elements was examined using RT-PCR, providing confirmation that they include expressed ncRNAs. Consistent with previous studies, these elements are significantly over-represented in the introns of transcription factors. Conclusions This study demonstrates a novel, highly effective, Bayesian approach to identifying conserved non-coding sequences. Our results complement previous findings that these sequences are enriched in transcription factors. However, in contrast to previous studies which suggest the majority of conserved sequences are regulatory factor binding sites, the majority of conserved sequences identified using our approach contain evidence of conserved RNA secondary structures, and our laboratory results suggest most are expressed. Functional roles at DNA and RNA levels are not mutually exclusive, and many of our elements possess evidence of both. Moreover, ncRNAs play roles in transcriptional and post-transcriptional regulation, and this may contribute to the over-representation of these elements in introns of transcription factors. We attribute the higher sensitivity of the pathway-focussed analysis compared to the genome-wide analysis to improved alignment quality, suggesting that enhanced genomic alignments may reveal many more conserved intronic sequences. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3645-2) contains supplementary material, which is available to authorized users.

Genetic research into complex diseases is frequently hindered by a lack of clear biomarkers for phenotype ascertainment. Phenotypes for such diseases are often identified on the basis of clinically defined criteria; however such criteria may not be suitable for understanding the genetic composition of the diseases. Various statistical approaches have been proposed for phenotype definition; however our previous studies have shown that differences in phenotypes estimated using different approaches have substantial impact on subsequent analyses. Instead of obtaining results based upon a single model, we propose a new method, using Bayesian model averaging to overcome problems associated with phenotype definition. Although Bayesian model averaging has been used in other fields of research, this is the first study that uses Bayesian model averaging to reconcile phenotypes obtained using multiple models. We illustrate the new method by applying it to simulated genetic and phenotypic data for Kofendred personality disorder—an imaginary disease with several sub-types. Two separate statistical methods were used to identify clusters of individuals with distinct phenotypes: latent class analysis and grade of membership. Bayesian model averaging was then used to combine the two clusterings for the purpose of subsequent linkage analyses. We found that causative genetic loci for the disease produced higher LOD scores using model averaging than under either individual model separately. We attribute this improvement to consolidation of the cores of phenotype clusters identified using each individual method.

A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.

Languages differ widely in the ways they encode time. I test the hypothesis that the languages that grammatically associate the future and the present, foster future-oriented behavior. This prediction arises naturally when well-documented effects of language structure are merged with models of intertemporal choice. Empirically, I find that speakers of such languages: save more, retire with more wealth, smoke less, practice safer sex, and are less obese. This holds both across countries and within countries when comparing demographically similar native households. The evidence does not support the most obvious forms of common causation. I discuss implications for theories of intertemporal choice. (JEL D14, D83, E21, I12, J26, Z13)

Mathematical modeling represents an important tool for analyzing cardiovascular function during spaceflight. This review describes how modeling of the cardiovascular system can contribute to space life science research and illustrates this process via modeling efforts to study postflight orthostatic intolerance (POI), a key issue for spaceflight. Examining this application also provides a context for considering broader applications of modeling techniques to the challenges of bioastronautics. POI, which affects a large fraction of astronauts in stand tests upon return to Earth, presents as dizziness, fainting and other symptoms, which can diminish crew performance and cause safety hazards. POI on the Moon or Mars could be more critical. In the field of bioastronautics, POI has been the dominant application of cardiovascular modeling for more than a decade, and a number of mechanisms for POI have been investigated. Modeling approaches include computational models with a range of incorporated factors and hemodynamic sophistication, and also physical models tested in parabolic and orbital flight. Mathematical methods such as parameter sensitivity analysis can help identify key system mechanisms. In the case of POI, this could lead to more effective countermeasures. Validation is a persistent issue in modeling efforts, and key considerations and needs for experimental data to synergistically improve understanding of cardiovascular responses are outlined. Future directions in cardiovascular modeling include subject-specific assessment of system status, as well as research on integrated physiological responses, leading, for instance, to assessment of subject-specific susceptibility to POI or effects of cardiovascular alterations on muscular, vision and cognitive function.