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Single-cell assays have enriched our understanding of hematopoiesis and, more generally, stem and progenitor cell biology. However, these single-end-point approaches provide only a static snapshot of the state of a cell. To observe and measure dynamic changes that may instruct cell fate, we developed an approach for examining hematopoietic progenitor fate specification using long-term (> 7-day) single-cell time-lapse imaging for up to 13 generations with in situ fluorescence staining of primary human hematopoietic progenitors followed by algorithm-assisted lineage tracing. We analyzed progenitor cell dynamics, including the division rate, velocity, viability, and probability of lineage commitment at the single-cell level over time. We applied a Markov probabilistic model to predict progenitor division outcome over each generation in culture. We demonstrated the utility of this methodological pipeline by evaluating the effects of the cytokines thrombopoietin and erythropoietin on the dynamics of self-renewal and lineage specification in primary human bipotent megakaryocytic-erythroid progenitors (MEPs). Our data support the hypothesis that thrombopoietin and erythropoietin support the viability and self-renewal of MEPs, but do not affect fate specification. Thus, single-cell tracking of time-lapse imaged colony-forming unit assays provides a robust method for assessing the dynamics of progenitor self-renewal and lineage commitment.

Expanding PrEP access necessitates training that supports healthcare providers’ progression along the PrEP implementation cascade, moving from PrEP awareness to prescription. We surveyed 359 USA providers about PrEP training content and format recommendations. We examined the association between cascade location and training recommendations. Most providers were aware of PrEP (100%), willing to prescribe PrEP (97.2%), had discussed PrEP with patients (92.2%), and had prescribed PrEP (79.9%). Latent class regression analysis revealed that cascade location was associated with training recommendations. Although all providers recommended PrEP-specific content (e.g., patient eligibility), providers who were located further along the cascade also recommended more comprehensive content, including sexual history-taking and sexual and gender minority competence training. Providers further along the cascade were also more likely to recommend interactive training formats (e.g., role-playing). These insights from providers furthest along the cascade indicate the importance of including comprehensive content and interactive formats in future PrEP training initiatives. Supplementary Information The online version contains supplementary material available at 10.1007/s10461-021-03375-w.

Abusive head trauma (AHT) is the most lethal form of child abuse; preventing AHT should be a national priority, but research into this area is woefully underfunded. Prevention programs have primarily focused on universal parent education during the neonatal period, a time when parents are a captive audience of the health care establishment whose focus is on the needs of their newborn infant, and who will soon be exposed to the frustration and anger of infant crying. Research has suggested a strong causal link between infant crying and AHT, and parents - particularly fathers and father figures - have been identified as the most common perpetrators of AHT. A number of studies have suggested that educating parents during the postnatal period about the normalcy of inconsolable infant crying and its evolution over the first several months of postnatal life improves parental knowledge about infant crying and a number of positive parenting behaviors, and decreases emergency room visits for crying. In 1998, we began a pilot program in Upstate New York near Buffalo that led to a 47% reduction in AHT incidence. Similar studies have demonstrated 35-75% reductions in incidence, which has led to enthusiasm for this approach to preventing AHT. We, as well as another group, have enacted statewide programs in Pennsylvania and North Carolina; unfortunately, these two large statewide replication trials failed to demonstrate any impact of such an intervention on AHT rates. Serial messages for parents, provided repeatedly over the period of greatest risk for AHT, might be another avenue of research.

This article reports on an exploration of how second-graders can learn mathematics through programming. We started from the theory that a suitably designed programming language can serve children as a language for expressing and experimenting with mathematical ideas and processes in order to do mathematics and thereby, with appropriate tasks and teaching, learn and enjoy the subject. This is very different from using the computer as a teaching app or a digital medium for exploration. Children tackled genuine puzzles – problems for which they did not already have a pre-learned solution. So far, we have built four microworlds for second-graders and tested them with a diverse population of well over three hundred children. The microworlds focus on the most critical second-grade mathematical content (as mandated in state standards), let children pick up all key programming ideas in contexts that make them ‘obvious’ (to maintain focus on the mathematics) and suppress all other distractions to minimize overhead for teachers or students using the microworlds. Because children see the results of the actions they articulate (in the computer language, Snap!), they can evaluate their methods and solutions themselves. The feedback is purely the outcome, not happy or sad sounds from the computer. Notably, nearly all children showed intense engagement, some choosing microworlds even outside of mathematics time. Teachers spontaneously reported this as well, with special mention of children whom they found hard to engage in regular lessons. We report our experiments and observations in the spirit of sharing the ideas and promoting more research.

Bloodstream infections (BSI) are significant causes of morbidity and mortality in cancer patients. These patients often receive 10 to 14 days of intravenous (IV) antibiotics. The objective of this study was to compare the outcomes of cancer patients transitioned from IV to oral (PO) therapy compared to continuation of IV treatment. This was a single-center, retrospective cohort study of hospitalized adult cancer patients with gram-negative bacteremia. Patients transitioned to a PO fluoroquinolone (FQ) within 5 days were allocated to the IV-to-PO group, while the remaining patients comprised the IV group. The primary outcome was the composite of treatment failure, defined as infection-related readmission, infection recurrence, or inpatient mortality. A multivariable logistic regression model was constructed to account for confounding variables. Secondary outcomes assessed included infection-related length of stay (LOS), hospital LOS, and adverse events, such as Clostridioides difficile infection and catheter-related complications. The IV-to-PO group included 78 patients, while the remaining 133 patients were allocated to the IV group. Differences at baseline included more hematologic malignancy, neutropenia, ICU admissions, and higher Pitt bacteremia scores in the IV group. The rate of treatment failure was significantly higher in the IV group (24% vs 9%; p < 0.01), which persisted in the logistic regression (aOR 3.5, 95% CI 1.3–9.1). The IV-to-PO group had decreased infection-related and hospital length of stay, as well as fewer catheter-related complications. The use of PO FQ may be considered for the definitive treatment of uncomplicated Enterobacterales BSI in cancer patients.

Local environments play influential roles in shaping individual and population-level outcomes. Yet, most literature and public health initiatives studying the built environment emphasize its role in environmental health or physical health but fail to consider its ability to influence social wellbeing. Rooted in a social determinant of health framework, this study investigates how a community’s social wellbeing is shaped by the built environment through exploring individuals’ social relationships and social interactions, specifically regarding experiences of social isolation, social loneliness, and social belonging, and the limitations or opportunities for such interactions and connections the environment imposes. Participants were selected from three geographic neighborhood tracts representing different combinations of median income, relative environment (rural versus urban) and access to available transportation and potential sites of social interaction. Collected participant data included social isolation and social loneliness scores, perceptions regarding community context and social belonging, and demographic factors (socio-structural factors). Through ANOVA and an OLS regression, our results suggest that while local built environments influence opportunities to encourage social wellbeing, socio-structural factors, such as marital status or income, can 1) overcome barriers related to physical access or 2) create additional barriers related to social access. Rather, the intersection of the community’s built environment and socio-structural factors interact to predict social isolation or social loneliness, influence perceptions related to objective accessibility, and is a potential determinant for social wellbeing, especially for socially disadvantaged individuals or households who are unable to access opportunities or spaces outside of their community.

Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has the potential to facilitate adherence and transform HIV prevention. However, little LAI PrEP research has occurred among women, who face unique barriers. We conducted 30 in-depth interviews with HIV-negative women from 2017-2018 across six sites (New York; Chicago; San Francisco; Atlanta; Washington, DC; Chapel Hill) of the Women's Interagency HIV Study. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Few women expressed interest in PrEP and when prompted to choose a regimen, 55% would prefer LAI, 10% daily pills, and 33% said they would not take PrEP regardless of formulation. Perceived barriers included: (1) the fear of new-and perceived untested-injectable products and (2) potential side effects (e.g., injection-site pain, nausea). Facilitators included: (1) believing shots were more effective than pills; (2) ease and convenience; and (3) confidentiality. Future studies should incorporate women's LAI PrEP-related experiences to facilitate uptake.

Genetic screening to inform personal risk has only recently become an option as the cost of sequencing decreases, and our ability to interpret sequence variants improves. Studies have demonstrated that people want to learn about their genetic information and do well after learning it, but minorities are underrepresented in these studies. We surveyed Ashkenazi Jewish (AJ) and Latino/a participants in a genetic screening study to solicit choices about genetic results to return, as well as their experience with learning these results and attitudes about genetic information secrecy and security. Participants had the option to proceed through the study self-guided, and few elected to have traditional pre-test genetic education and counseling. Despite this, the majority were satisfied with the process of selecting and receiving genetic results and felt that they understood their results. Concerns about privacy and confidentiality of genetic data were minimal, though some participants expressed modest concerns about keeping any potential results secret or the confidentiality of their genetic information. Our results support the feasibility of the option of self-guided genetic screening. Additional care will need to be taken when designing population-based screening studies to meet the needs of participants who come from communities with different experiences with genetics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12687-020-00464-6) contains supplementary material, which is available to authorized users.

Previous studies have found increased smoking prevalence amongst adults with anorexia nervosa (AN) compared to the general population. The current investigation explored bidirectional associations between AN and smoking behaviour (initiation and heaviness), to address questions surrounding causation. In Study One, logistic regression models with variance robust standard errors assessed longitudinal associations between AN and smoking, using data from adolescent participants of the Avon Longitudinal Study of Parents and Children (N = 5100). In Study Two, two-sample Mendelian randomisation (MR) tested possible causal effects using summary statistics from publicly available genome-wide association studies (GWAS). Study One provided no clear evidence for a predictive effect of AN on subsequent smoking behaviour, or for smoking heaviness/initiation predicting later AN. MR findings did not support causal effects between AN and smoking behaviour, in either direction. Findings do not support predictive or causal effects between AN and smoking behaviour. Previously reported associations may have been vulnerable to confounding, highlighting the possibility of smoking and AN sharing causal risk factors.

BACKGROUND: Little is known about patients who have caregiver proxies communicate with healthcare providers via portal secure messaging (SM). Since proxy portal use is often informal (e.g., sharing patient accounts), novel methods are needed to estimate the prevalence of proxy-authored SMs. OBJECTIVE: (1) Develop an algorithm to identify proxy-authored SMs, (2) apply this algorithm to estimate predicted proxy SM (PPSM) prevalence among patients with diabetes, and (3) explore patient characteristics associated with having PPSMs. DESIGN: Retrospective cohort study. PARTICIPANTS: We examined 9856 patients from Diabetes Study of Northern California (DISTANCE) who sent ≥ 1 English-language SM to their primary care physician between July 1, 2006, and Dec. 31, 2015. MAIN MEASURES: Using computational linguistics, we developed ProxyID, an algorithm that identifies phrases frequently found in registered proxy SMs. ProxyID was validated against blinded expert categorization of proxy status among an SM sample, then applied to identify PPSM prevalence across patients. We examined patients’ sociodemographic and clinical characteristics according to PPSM penetrance, “none” (0%), “low” (≥ 0–50%), and “high” (≥ 50–100%). KEY RESULTS: Only 2.3% of patients had ≥ 1 registered proxy-authored SM. ProxyID demonstrated moderate agreement with expert classification (Κ = 0.58); 45.7% of patients had PPSMs (40.2% low and 5.5% high). Patients with high percent PPSMs were older than those with low percent and no PPSMs (66.5 vs 57.4 vs 56.2 years, p

To create a comprehensive view of ecosystem resource use, we integrated parallel resource use efficiency observations into a multiple-resource use efficiency (mRUE) framework using a dynamic factor analysis model. Results from 56 site-years of eddy covariance data and mRUE factors for a site in the US Midwest show temporal dynamics and coherence (using Pearson’s R) among resources are associated with interannual variation in precipitation. Loading factors are derived from mRUE observations and quantify how strongly data are connected to the underlying ecosystem state. Water and light resource use loading factors are coherent at annual timescales (Pearson’s R of 0.86), whereas declining patterns of carbon use efficiency loading factors highlight the ecosystem’s trade-off between carbon uptake and respiration during the growing season. At annual and monthly timescales, influence decreases from ~ 85 to ~ 65% for loading factors for carbon use, while influence of light use loading factors peaks to ~ 60% at growing season timescales. Quantifying variation in ecosystem function provides novel insights into the temporal dynamics of changing importance of multiple resources to ecosystem function.

The objective of this study was to predict the competitive adsorption of As(III), As(V), and PO4 by an iron oxide impregnated carbon (L-Act, 9% Fe(III) amorphous iron oxide) over a range of environmental conditions using the surface complexation modeling (SCM) approach. L-Act surface complexation constants determined from a single pH-adsorption edge were used to predict pH-dependent competitive removal in singular, binary, and tertiary adsorbate systems. As(III), As(V), and PO4 complexes were modeled as bidentate binuclear species at low pH and monodentate species at high pH using the two monoprotic surface site/diffuse electric double layer model (2MDLM). F values determined based on 2MDLM predictions were close to those calculated by FITEQL (a statistical optimization program) demonstrating the effectiveness of the 2MDLM in describing adsorption behavior. F values were generally in the recommended range of 0.1–20 indicating a good fit between the data and the model. The 2MDLM also successfully predicted As(III)/As(V)/PO4 adsorption data of hydrous ferric oxide and goethite adsorbents from the literature.

The remoteness of the northern Great Barrier Reef makes observations of environmental change and coral health sparse, but provides opportunities for paleoclimate and paleoecology proxies to contribute new insights into coral health in a changing climate. These proxies include geochemical measures (δ18O, δ13C, and Sr/Ca) that track sea surface temperature (SST), salinity, and physiological processes; luminescence, which records freshwater input; and annual growth parameters (density, extension, and calcification). Merging these approaches provides insight into the historical role of environmental variability in coral health. This study uses Porites spp. corals from five sites on the northern Great Barrier Reef (12–13.5°S) to produce combined monthly resolved records of geochemistry, growth banding, and luminescence between 1972 and 2008. We demonstrate that SST reconstructed from Sr/Ca accurately captures Indo-Pacific Warm Pool variability, and hydrological proxies (luminescence and seawater δ18O) accurately reconstruct summer rainfall and river discharge in nearshore corals. Concurrent Sr/Ca minima and density and luminescence peaks from two sites demonstrate that high-density bands are generally formed during summer at these sites, which aids the development of future coral paleoclimate and paleoecology chronologies. Regional hydrological proxies showed more consistent responses to El Nino–Southern Oscillation (ENSO) events than SST proxies, in agreement with instrumental data. Because these corals, like instrumental records, show no consistently large ENSO heat extremes, we find no consistent growth anomalies during historical ENSO events. Our results highlight the unusual nature of recent widespread and severe coral bleaching and establish groundwork for exploring the response of northern GBR corals to past climate variations.

Wetlands play a disproportionately large role in global terrestrial carbon stocks, and from 1 year to the next individual wetlands can fluctuate between carbon sinks and sources depending on factors such as hydrology, temperature, and land use. Although much research has been done on short-term seasonal to annual wetland biogeochemical cycles, there is a lack of experimental evidence concerning how the reversibility of wetland hydrological changes will influence these cycles over longer time periods. Five years of drought-induced declining water table at Lost Creek, a shrub fen wetland in northern Wisconsin, coincided with increased ecosystem respiration (Reco) and gross primary production (GPP) as derived from long-term eddy covariance observations. Since then, however, the average water table level at this site has increased, providing a unique opportunity to explore how wetland carbon fluxes are affected by interannual air temperature differences as well as changing water table levels. Water table level, as measured by water discharge, was correlated with Reco and GPP at interannual time scales. However, air temperature had a strong correlation with Reco, GPP, and net ecosystem productivity (NEP) at monthly time scales and correlated with NEP at inter-annual time scales. Methane flux was strongly temperature-controlled at seasonal time scales, increasing an order of magnitude from April to July. Annual methane emissions were 51 g C m−2. Our results demonstrate that over multi-year timescales, water table fluctuations can have limited effects on wetland net carbon fluxes and instead at Lost Creek annual temperature is the best predictor of interannual variation.

Background Descriptive studies examining publication rates and citation counts demonstrate a geographic skew toward high-income countries (HIC), and research from low- or middle-income countries (LMICs) is generally underrepresented. This has been suggested to be due in part to reviewers’ and editors’ preference toward HIC sources; however, in the absence of controlled studies, it is impossible to assert whether there is bias or whether variations in the quality or relevance of the articles being reviewed explains the geographic divide. This study synthesizes the evidence from randomized and controlled studies that explore geographic bias in the peer review process. Methods A systematic review was conducted to identify research studies that explicitly explore the role of geographic bias in the assessment of the quality of research articles. Only randomized and controlled studies were included in the review. Five databases were searched to locate relevant articles. A narrative synthesis of included articles was performed to identify common findings. Results The systematic literature search yielded 3501 titles from which 12 full texts were reviewed, and a further eight were identified through searching reference lists of the full texts. Of these articles, only three were randomized and controlled studies that examined variants of geographic bias. One study found that abstracts attributed to HIC sources elicited a higher review score regarding relevance of the research and likelihood to recommend the research to a colleague, than did abstracts attributed to LIC sources. Another study found that the predicted odds of acceptance for a submission to a computer science conference were statistically significantly higher for submissions from a “Top University.” Two of the studies showed the presence of geographic bias between articles from “high” or “low” prestige institutions. Conclusions Two of the three included studies identified that geographic bias in some form was impacting on peer review; however, further robust, experimental evidence is needed to adequately inform practice surrounding this topic. Reviewers and researchers should nonetheless be aware of whether author and institutional characteristics are interfering in their judgement of research.

The present study examines the impact of previous sexual victimization on emotional distress in a sample of women (n = 492) involved in a sexual harassment class action lawsuit. Sexual harassment was found to predict symptoms of PTSD and general symptoms of anxiety, over and above the effects of previous victimization and other relevant personal variables; it also predicted depression and self-esteem, although previous victimization had a stronger impact on these variables than did sexual harassment. The effects of previous victimization and sexual harassment on emotional distress appeared to be independent and cumulative. The legal and clinical relevance of these findings are discussed.

The giraffid fossils recovered from ~ 2.8–2.6 million year old (Ma) sediments from Lee Adoyta, Ledi-Geraru, Ethiopia, are described here. Sivatherium maurusium and Giraffa cf. G. gracilis are the two identified taxa, with the former being more abundant than the latter. We interpret this skew of relative abundance to be of paleoenvironmental significance, as Sivatherium is rare and Giraffa is common in the adjacent, but older sediments of the Hadar Formation at Hadar (~ 3.4 to 2.95 Ma), which was characterized by wooded and well-watered habitats through most of its sequence. Stable carbon isotope analyses show that Giraffa remained an obligate browser throughout the lower Awash Valley (LAV) sequence while Sivatherium underwent a dietary transition from a browser in the Hadar Formation to a grazer at Lee Adoyta. This dietary shift in Sivatherium reflects local environmental change through time in the LAV as open habitats spread during the late Pliocene. A compilation of isotopic data from other sites in eastern Africa shows that the LAV dietary shift in Sivatherium occurred roughly one million years earlier than in the Turkana Basin, Kenya, reflecting a spatiotemporally staggered expansion of C4 vegetation across eastern Africa.

Establishing the relationship between craniodental morphology and dietary ecology in extant species permits inferences to be made about the ecology and biology of fossil species and the habitats they inhabited. Previous work linking diet and craniodental morphology has historically relied upon categorical classifications of diet and has not considered the phylogenetic signal (i.e., non-independence) of morphology due to shared evolutionary history. Here we use phylogenetic comparative methods to analyze the relationship between diet and eight craniodental indices for 40 species of African Bovidae using both categorical and continuous (stable carbon isotopes of enamel, δ13C) classifications of diet. In addition, we examine three modes of evolution that best explain interspecific variation in each of these indices, including: Brownian Motion (BM), Early Burst (EB), and Ornstein-Uhlenbeck (OU). Our results show that the hypsodonty index (HI), the length of the masseteric fossa relative to facial depth (MAS-F), and the length of the diastema relative to the total toothrow length (DIAS-TR) are the best predictors of diet among African bovids. These indices are best explained by either a BM or OU mode of evolution. Our findings have important implications for understanding the evolution of craniodental traits and reconstructing the diet of fossil mammals, especially bovids.

Background Portfolio effects were first described as a basis for mitigating against financial risk by diversifying investments. Distributing investment across several different assets can stabilize returns and reduce risks by statistical averaging of individual asset dynamics that often correlate weakly or negatively with each other. The same simple probability theory is equally applicable to complex ecosystems, in which biological and environmental diversity stabilizes ecosystems against natural and human-mediated perturbations. Given the fundamental limitations to how well the full complexity of ecosystem dynamics can be understood or anticipated, the portfolio effect concept provides a simple framework for more critical data interpretation and pro-active conservation management. Applied to conservation ecology purposes, the portfolio effect concept informs management strategies emphasizing identification and maintenance of key ecological processes that generate complexity, diversity and resilience against inevitable, often unpredictable perturbations. Implications Applied to the reciprocal goal of eliminating the least valued elements of global biodiversity, specifically lethal malaria parasites and their vector mosquitoes, simply understanding the portfolio effect concept informs more cautious interpretation of surveillance data and simulation model predictions. Malaria transmission mediated by guilds of multiple vectors in complex landscapes, with highly variable climatic and meteorological conditions, as well as changing patterns of land use and other human behaviours, will systematically tend to be more resilient to attack with vector control than it appears based on even the highest quality surveillance data or predictive models. Conclusion Malaria vector control programmes may need to be more ambitious, interpret their short-to-medium term assessments of intervention impact more cautiously, and manage stakeholder expectations more conservatively than has often been the case thus far.

Background The importance of contextual factors in influencing quality improvement and implementation (QI&I) initiatives is broadly acknowledged. Existing treatments of context have primarily viewed it as static and distinct from interventions themselves. The objective of this study was to advance understanding of the complex and dynamic interaction between context, intervention, and implementation strategies. Using the Model for Understanding Success in Quality (MUSIQ), we aimed to better understand the roles of, and inter-relationships between, contextual factors within QI&I initiatives. Methods Secondary analysis was performed on qualitative data collected as part of two studies: (1) an evaluation of a state-wide obstetrical quality improvement (QI) initiative, and (2) a study of the use of Plan-Do-Study-Act cycle method in QI projects. Electronic coding databases from each study were reviewed jointly. Data analysis was initiated deductively using MUSIQ as a template. Codes were added in an inductive manner. Results All original factors in MUSIQ were observed to be important in the QI initiatives studied and new factors were identified. Three distinct types of context were identified; the setting(s) of care in which QI&I takes place (Type 1); the context of the team conducting a specific project (Type 2); and the wider context supporting general QI&I (Type 3). The picture of context emerging from this study is a dynamic one with multiple, closely-linked factors operating at different levels in a system that is constantly changing in response to QI&I initiatives. To capture this complexity, a revised model (MUSIQ v2.0) was created positioning use of structured QI&I approaches as the focal point and demonstrating how context influenced effective use of these approaches, and in turn, how these approaches supported teams in navigating context by adapting interventions to fit local settings. Conclusions MUSIQ is a useful tool to explore the roles of, and inter-relationships between, contextual factors within QI&I initiatives. The revised model may help address some existing controversies about how context influences QI&I success and help ensure that future research efforts consider context not as static background, but as a complex system that is constantly changing, tightly-linked, and governed by feedback loops. Electronic supplementary material The online version of this article (10.1186/s12913-018-3348-7) contains supplementary material, which is available to authorized users.

Concussion literature and treatment guidelines are inconclusive regarding the role of sex in symptom reporting at baseline and post-concussion. Although empirical evidence is lacking, it is generally regarded that females have a more severe symptomatic presentation than males at all time-points on the concussion spectrum. Our objective was to determine whether differences exist between males and females at baseline (pre-season/before concussion) or post-concussion for self-reported (1) prevalence of individual symptoms and (2) total symptom scores in high school and college athletes. Systematic review and meta-analysis of observational cohort studies; level of evidence, 1. A computerized search of the PubMed, SPORTDiscus, CINAHL, and Scopus databases was performed. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Criteria for inclusion were (1) self-report of symptoms at any time within the concussion spectrum, including baseline and after concussion, (2) study sample included high school and/or collegiate athletes aged 12–26 years, (3) concussions occurred during participation in sport, and (4) symptom reporting was separated by sex. The Quality Assessment Tool for Cohort Studies, Q-Coh, was utilized for quality assessment. Twenty-one studies met the criteria for inclusion: seventeen had good quality and four, acceptable quality. At baseline, females had significantly higher odds than males of reporting the individual symptoms of vision/hearing problems, headache/migraine, difficulty concentrating, energy/sleep disturbances, and emotional disturbances. Post-concussion, only one symptom demonstrated significant differences between males and females, with females demonstrating lower odds of reporting confusion than males. Statistically, at baseline and post-concussion, females had significantly higher total symptom scores on the Post-Concussion Scale (PCS) and the Sport Concussion Assessment Tool 2 (SCAT2), but when the standard mean difference was interpreted after back-transformation, these results were clinically insignificant. The symptomatic presentation of males and females, most notably the prevalence of specific symptoms, is very divergent. Females had higher total symptom scores at baseline and post-concussion, however, clinically this cannot be interpreted as a meaningful difference. It is possible that these differences can be explained by normal hormonal changes associated with the menstrual cycle. The implications of these findings are that symptomatic presentation during an individual female’s menstrual cycle needs to be taken into consideration post-concussion when making return-to-play decisions, as returning to a completely asymptomatic level may not be a reasonable expectation.

Farmed fish are typically genetically different from wild conspecifics. Escapees from fish farms may contribute one-way gene flow from farm to wild gene pools, which can depress population productivity, dilute local adaptations and disrupt coadapted gene complexes. Here, we reanalyse data from two experiments (McGinnity et al., 1997, 2003) where performance of Atlantic salmon (Salmo salar) progeny originating from experimental crosses between farm and wild parents (in three different cohorts) were measured in a natural stream under common garden conditions. Previous published analyses focussed on group-level differences but did not account for pedigree structure, as we do here using modern mixed-effect models. Offspring with one or two farm parents exhibited poorer survival in their first and second year of life compared with those with two wild parents and these group-level inferences were robust to excluding outlier families. Variation in performance among farm, hybrid and wild families was generally similar in magnitude. Farm offspring were generally larger at all life stages examined than wild offspring, but the differences were moderate (5–20%) and similar in magnitude in the wild versus hatchery environments. Quantitative genetic analyses conducted using a Bayesian framework revealed moderate heritability in juvenile fork length and mass and positive genetic correlations (>0.85) between these morphological traits. Our study confirms (using more rigorous statistical techniques) previous studies showing that offspring of wild fish invariably have higher fitness and contributes fresh insights into family-level variation in performance of farm, wild and hybrid Atlantic salmon families in the wild. It also adds to a small, but growing, number of studies that estimate key evolutionary parameters in wild salmonid populations. Such information is vital in modelling the impacts of introgression by escaped farm salmon.

Understanding the factors influencing the diversity of primate communities is important for studies of primate evolutionary history, primate behavioral ecology, and the development of conservation strategies. Previous research on primate communities has focused on a variety of questions including explaining variation in species richness, biomass, and taxonomic composition (Kamilar and Beaudrot 2013; Reed and Bidner 2004), but with less attention given to the role of spatial scale in structuring communities, interactions between primates and other taxa, or evolutionary history. In recent years, there have been important advances in GIS, ecological informatics, macroecology, and phylogenetics, which have enabled scientists to revisit classic questions and address new questions in community ecology. This research has focused attention on the importance of variation in spatial, temporal, and phylogenetic scales for structuring communities (Beaudrot and Marshall 2011; Beaudrot et al. 2013; Gavilanez and Stevens 2013; Kamilar and Ledogar 2011; Kamilar and Muldoon 2010; Lehman 2006). The articles in this special issue of the International Journal of Primatology are based on a symposium at the 2013 American Association of Physical Anthropologists Meeting at Knoxville, Tennessee. The special issue includes a wide variety of perspectives to understand the diversity of primate communities across a variety of scales. The Int J Primatol (2014) 35:1083–1087 DOI 10.1007/s10764-014-9804-2

Many factors contribute to the structure of primate communities, including historical processes, interspecific competition, and climate. Here, we quantify the phylogenetic structure of individual primate communities to evaluate these factors relative to a null model. Then, we examine the effects of species richness and local climate on variation in community phylogenetic structure. We analyze 71 haplorhine and 29 strepsirrhine communities in Africa and quantify their net relatedness (NRI) and nearest taxon (NTI) indices. Significantly low, i.e., phylogenetically even, NRI and NTI values are indicative of interspecific competition in the past, resulting in closely related species not being found in the same community. In contrast, significantly high, i.e., phylogenetically clustered, NRI and NTI values suggest that closely related species have similar ecological requirements, resulting in closely related species occupying the same community. In a second set of analyses, we used simultaneous autoregressive models to examine if species richness, rainfall, and temperature predict variation in community phylogenetic structure. Most individual communities exhibited phyloge- netically random species assemblages. However, significantly structured haplorhine

Recent studies have demonstrated that dispersal limitation, which refers to the limited ability of individuals to reach distant geographic areas, is an important influence on the species that are found in primate assemblages. In this study, we investigate the relative influences of dispersal limitation and environmental filtering in 131 African primate assemblages in 9 biogeographic regions throughout sub-Saharan Africa. Specifically, we evaluate the dispersal-ecological specialization hypothesis, which posits that there are trade-offs between dispersal ability and ecological specialization that are influenced by climatic variation along latitudinal gradients. The hypothesis predicts that species in assemblages near the equator, where climatic conditions are more stable, will exhibit stronger dispersal limitation and greater ecological specialization than species within assemblages located further from the equator, where climate is more variable. In contrast, assemblages located at higher latitudes are expected to be influenced more strongly by environmental filtering than dispersal limitation. We used hierarchical cluster analysis to identify regions, conducted partial Mantel tests to evaluate the contributions of dispersal limitation and environmental filtering in each region, and evaluated predictors of those contributions with linear regression. In all regions, dispersal limitation was a stronger predictor of community similarity than was environmental filtering, yet the strength of dispersal limitation varied. Dispersal limitation was greatest at low latitudes and declined with increasing absolute latitude. Thus, primate assemblages exhibited a significant latitudinal gradient in dispersal limitation, but not in environmental filtering. These results support aspects of the dispersal-ecological specialization hypothesis and call for future mechanistic studies to address this broad-scale pattern.

Continuous manufacturing can be benefited by the use of the Quality by Design (QbD) strategy for robust process development and by the use of Process Analytical Technology (PAT) for real-time process monitoring and control. A successful implementation of QbD and PAT for continuous processes relies on a robust and information-rich process model as a basis for process understanding, monitoring, and control. Compared to first principles and other empirical models, a latent variables-based process model is capable of decomposing multidimensional process data into a few orthogonal latent variables and of providing accessible process understanding/visualization and control within the latent variable space. This study is an extension of our group’s earlier effort (Liu et al., J Pharm Innov 6:170–180, 2011) to explore the utility of latent variables-based process modeling in pharmaceutical manufacturing processes. The case presented here is the first application of latent variables-based modeling to a reaction process in small-molecule active pharmaceutical ingredient route synthesis, i.e., a continuous-flow hydrogenation. A particular reactor configuration and operation was used in this proof-of-concept study. It was found that time-variant profiles of pressure in the flow tube reactor served as an effective indicator of gas–liquid interaction within the reactor, thus determining process outcomes, i.e., the extent of reaction and enantiomeric excess (ee), given the importance of process set points. In addition, a design space of process parameters predicted to produce optimal outcomes, i.e., extent of reaction greater than 98 % and ee higher than 93 %, was established in order to provide a flexible operation space for performing the reaction with desired process outcomes. The capabilities of latent variables-based process modeling have been well demonstrated as applied to a continuous-flow hydrogenation reaction, regarding its improved process understanding and the potential for process optimization & control as well. Future efforts will be focused on continuing understanding of the capabilities and limitations of such a methodology on a fully-automated control scheme for continuous flow reaction.

A1 Introduction to the 8th Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers1, Lisa Simpson2 1Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA; 2AcademyHealth, Washington, DC, 20036, USA For the second year in a row, we are pleased to be able to share the proceedings of the Annual Conference on the Science of Dissemination and Implementation in Health, a large meeting reflecting the expanding and evolving research field that seeks to optimize the use of evidence, interventions, and tools from health research within the myriad of settings where people receive health care, make health-related decisions, and increase knowledge of influences on the health of the population. We once again benefitted from a strong partnership, co-led by AcademyHealth and the National Institutes of Health (NIH), with co-sponsorship from the Agency for Healthcare Research and Quality (AHRQ), the Patient Centered Outcomes Research Institute (PCORI), the Robert Wood Johnson Foundation (RWJF), the US Department of Veterans Affairs (VA), and the WT Grant Foundation. In addition, we benefitted from the collaboration of staff from the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). NIH and AcademyHealth again co-led the program planning committee, which focused on the development of the plenary sessions, and convened a scientific advisory panel to suggest speakers and advise on the overall conference development. The planning committee identified four key areas around which to focus the plenary panels and keynote address. Dr. America Bracho, M.D., M.P.H., Executive Director of Latino Health Access in Orange County, California, spoke about the opportunities for implementation science to inform efforts to improve community health and engage underserved populations. The three plenary panels each focused on a significant future direction for dissemination and implementation (D & I) research: the interface between D&I science and population health, emerging opportunities for global implementation science, and the challenges around implementation of precision medicine. The plenary sessions were complemented by facilitated lunchtime discussions on the same three topics, which offered participants an opportunity to identify key research questions for each and brainstorm next steps. Synopses of the lunchtime discussions are included in this supplement. Given the overwhelming success of the 2014 conference and the large number of abstracts received in 2014 (660), the program planning committee identified eight program tracks for abstract submitters to respond to, and through which the concurrent sessions of the conference would be organized. These tracks—Behavioral Health, Big Data and Technology for Dissemination and Implementation Research, Clinical Care Settings, Global Dissemination and Implementation, Promoting Health Equity and Eliminating Disparities, Health Policy Dissemination and Implementation, Prevention and Public Health, and Models, Measures and Methods— were designed to enable conference participants to follow a consistent theme across the multiple sessions of the conference and form the structure of this supplement. The call for abstracts, including individual paper presentations, individual posters and panel presentations, resulted in 515 submissions, spread across the eight thematic tracks. Over one hundred reviewers devoted their time to ensuring a comprehensive and expert review, and reviews were conducted within each track and coordinated by the track leads. For the final program, 64 oral presentations, 12 panels, and 263 posters were presented over the two-day meeting. Slides for the oral presentations and panels (with the agreement of the authors) were posted on the conference website (http://diconference.academyhealth.org/archives/2015archives) and all abstracts were included on the conference webapp (https://academyhealth.confex.com/academyhealth/2015di/meetingapp.cgi). This supplement has compiled the abstracts for presented papers, panel sessions, and lunchtime discussions from the 8th Annual Meeting on the Science of Dissemination and Implementation in Health: Optimizing Personal and Population Health. We are pleased to have the abstracts from the conference together in one volume once again, and look forward to the 9th Annual meeting, scheduled for December in Washington, D.C.

In response to federal administrative rule, the Tahoe National Forest (TNF), California, USA engaged in trail-route prioritization for motorized recreation (e.g., off-highway-vehicles) and other recreation types. The prioritization was intended to identify routes that were suitable and ill-suited for maintenance in a transportation system. A recreational user survey was conducted online (n = 813) for user preferences for trail system characteristics, recreational use patterns, and demographics. Motorized trail users and non-motorized users displayed very clear and contrasting preferences for the same system. As has been found by previous investigators, non-motorized users expressed antagonism to motorized use on the same recreational travel system, whereas motorized users either supported multiple-use routes or dismissed non-motorized recreationists' concerns. To help the TNF plan for reduced conflict, a geographic information system (GIS) based modeling approach was used to identify recreational opportunities and potential environmental impacts of all travel routes. This GIS-based approach was based on an expert-derived rule set. The rules addressed particular environmental and recreation concerns in the TNF. Route segments were identified that could be incorporated into minimal-impact networks to support various types of recreation. The combination of potential impacts and user-benefits supported an optimization approach for an appropriate recreational travel network to minimize environmental impacts and user-conflicts in a multi-purpose system.

The extensive literature documenting the ecological effects of roads has repeatedly implicated noise as one of the causal factors. Recent studies of wildlife responses to noise have decisively identified changes in animal behaviors and spatial distributions that are caused by noise. Collectively, this research suggests that spatial extent and intensity of potential noise impacts to wildlife can be studied by mapping noise sources and modeling the propagation of noise across landscapes. Here we present models of energy extraction, aircraft overflight and roadway noise as examples of spatially extensive sources and to present tools available for landscape scale investigations. We focus these efforts in US National Parks (Mesa Verde, Grand Teton and Glacier) to highlight that ecological noise pollution is not a threat restricted to developed areas and that many protected natural areas experi- ence significant noise loads. As a heuristic tool for understanding past and future noise pollution we forecast community noise utilizing a spatially-explicit land-use change model that depicts the intensity of human development at sub-county resolution. For road noise, we transform effect distances from two studies into sound levels to begin a discussion of noise thresholds for wildlife. The spatial scale of noise exposure is far larger than any protected area, and no site in the continental US is free form noise. The design of observational and experimental studies of noise effects should be informed by knowledge of regional noise exposure patterns.

Ammonia oxidation is a central process in the nitrogen cycle. Particularly in marine and estuarine environments, few experiments have been conducted to tease apart the factors influencing their abundance and composition. To investigate the effect of nitrogen and phosphorus availability on ammonia-oxidizing bacteria (AOB), we conducted a nutrient enrichment experiment in a Maine salt marsh and sampled sediment communities in three seasons over 2 years. We assessed community composition using terminal restriction fragment length polymorphism analysis and sequencing of cloned fragments of the ammonia monooxygenase (amoA) gene. Almost all of the amoA sequences fell within the marine and estuarine-specific Nitrosospira-like clade. Applied separately, nitrogen and phosphorus significantly altered AOB composition; however, together the nutrients had an interactive effect, and composition did not change. In contrast, nutrient enrichment did not alter AOB abundance. Furthermore, the response of AOB composition to nutrient enrichment varied over time. We conclude that closely related taxa within the marine/estuarine-specific Nitrosospira-like clade vary in their preference for nutrient concentrations, and this preference may depend on other temporally variable abiotic factors. Finally, AOB composition was highly variable within and across years even in untreated plots. Further studies are needed to test how these different aspects of compositional variability in AOB communities influence nitrogen cycling.

Proteases--both endogenous proteases from the coagulation cascade, mast cells, and respiratory epithelial trypsin, and exogenous proteases from parasites, insects, mites, molds, pollens, and other aeroallergens--stimulate a tissue response that includes attraction and activation of eosinophils and neutrophils, degranulation of eosinophils and mast cells, increased response of afferent neurons, smooth muscle contraction, angiogenesis, fibrosis, and production of immunoglobulin E. This response to exogenous proteases can be considered a form of innate immunity directed against multicellular organisms. The response of the airways to environmental proteases very closely resembles the response to airborne allergens. Although clinical research in this area is just beginning, the response to environmental proteases appears to be important in the pathogenesis of rhinitis and asthma developing from damp, water-damaged buildings, and intrinsic asthma with its associated rhinosinusitis and polyps.

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal–epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT–polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.

Free-living plant growth-promoting rhizobacteria (PGPR) can be used in a variety of ways when plant growth enhancements are required. The most intensively researched use of PGPR has been in agriculture and horticulture. Several PGPR formulations are currently available as commercial products for agricultural production. Recently developing areas of PGPR usage include forest regeneration and phytoremediation of contaminated soils. As the mechanisms of plant growth promotion by these bacteria are unravelled, the possibility of more efficient plant-bacteria pairings for novel and practical uses will follow. The progress to date in using PGPR in a variety of applications with different plants is summarized and discussed here.

In recent years, fish kills along the mid-Atlantic US coast have become an increasing problem, with important economic, environmental, and public health implications (Glasgow and others 1995; Burkholder 1998; Grattan and others 1998; Haselow and others 2001; Shoemaker and Hudnell 2001). Research into the causes of these fish kills is ongoing, and monitoring and surveillance programs have been instituted to investigate (among other factors) the role of actively toxic forms of two known species within the dinoflagellate genus Pfiesteria (Burkholder and others 1995, 2001a; Steidinger and others 1996; Burkholder and Glasgow 1997; Glasgow and others 2001b). In their recent analyses of the relationship between Pfiesteria and fish kills, Burkholder and others (1999) and Stow (1999) stated, as others have noted previously (Meyer and Barclay 1990), that it is difficult to establish the causes of estuarine fish kills at the ecosystem level. The evaluation of Burkholder and others (1999) was based on the biology and toxic behavior of Pfiesteria, as well as empirical sampling of field fish kill events then in progress, as supported by laboratory analyses of samples collected from each fish kill. In contrast, Stow (1999) conducted theoretical probability calculations and argued that information demonstrating the presence of toxic Pfiesteria during fish kills was insufficient to prove that there was a cause-and-effect

Patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus should undergo computed tomography of the chest and abdomen and positron emission tomography to look for evidence of distant metastatic disease. In the absence of systemic metastases, locoregional staging should be performed with endoscopic ultrasonography and fine needle aspiration of accessible periesophageal lymph nodes and any detectable celiac lymph nodes. Patients found to have T3 tumors (transmural extension), T4 tumors (invasion of adjacent structures), or N1-M1a (lymph node-positive) disease do poorly when treated with surgery alone; 5-year survival is less than 20%. These patients should be considered for combined modality therapy. Patients with T4 disease are generally not deemed candidates for surgical resection; they may be considered for definitive chemoradiotherapy. Patients with T3 disease or lymph node-positive disease may be treated with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy alone. Patients considered for trimodality therapy should be fully restaged before surgery to assess their response to neoadjuvant treatment. This should include repeat endoscopic ultrasound and fine needle aspiration of lymph nodes. Patients whose lymph node metastases do not completely respond to neoadjuvant therapy are unlikely to benefit from the addition of surgery. Patients with persistently positive celiac lymph nodes have a very poor prognosis and should not undergo surgery. Patients with persistent nodal disease who have good performance status may be considered for additional chemotherapy. Patients with locally advanced esophageal cancer who have poor performance status are not good candidates for combined modality therapy. These individuals are best managed with palliative intent. Particular attention should be given to alleviating the common problem of dysphagia, which causes significant morbidity.

An image processing system developed to support examination of computed tomographic colonoscopy (CTC) was developed in 1995. The clinical viability of CTC is enhanced by the solution of several technical problems. These problems include the limited detectability of sessible polyps and difficulties in discrimination between polypoid masses and retained stool. CTC is also made more feasible by simplifying the required colon preparation and reducing the time required to analyze scan results. Each of these challenges have been addressed by enhancements to the CTC analysis workstation software. Endoluminal volume rendering has been enhanced by the addition of automatic segmentation to facilitate analysis of colon segments, which contain tagged liquid stool. By automating this function, the system is able to process scans that are acquired following a wide variety of colon preparation protocols. Similar approaches have been used to identify retained stool. Automatic tissue characterization has also been incorporated into the volume rendering routines to help identify and diagnose polypoid masses. These enhancements have improved the quality of CTC interpretation, while reducing the time required to perform the analysis. This time reduction was necessary to reduce the cost of CTC enough to make it viable for asymptotic population screening. To date, over 150 patient examinations have been performed using this new technique. A recent blinded, prospective study reporting the results from two independent observers has been presented. The technique is feasible, reliable, and has been implemented clinically with results reported within 1 hour of the examination.

Background: Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of thep53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency ofp53 overexpression in this region both in patients with SCCE and in normal subjects. Methods: Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to thep53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of thep53 gene was amplified via polymerase chain reaction and sequenced. Results: Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate forp53 over-expression. The corresponding normal samples showed that three (33%) hadp53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayedp53 overexpression in seven (39%). Eight of the nine tumors hadp53 mutations. Conclusions: p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region.

An analysis of the tensile deformation behavior of a two-phase body-centered cubic (bcc)-hexagonal close-packed (hcp) alloy, Ti-6Al-4V, has been made. This has shown that the temperature dependence of the flow stress, the logarithm of the effective stress, and the strain-rate sensitivities can be described by simple analytical equations if the thermally activated strain-rate equation contains the Yokobori activation enthalpy H = H{sup 0} ln ({sigma}*{sub 0}/{sigma}*), where H{sup 0} is a constant, {sigma}* the effective stress, and {sigma}*{sub 0} its 0 K value. The flow stress-temperature plateau region (500 to 600 K) also can be rationalized analytically in terms of oxygen dynamic strain aging in the alpha phase.

There have been reported epidemics of severe asthma in Barcelona, Spain, linked to a 10 kDa low molecular mass (LMM) allergen from soybean hulls that became airborne during unloading of ships. As a preliminary probe of the potential for dispersion of this allergen in USA cities, four automated air samplers were placed around a grain elevator in New Orleans and operated continuously from May to October 1990. The allergen was extracted from the filters and immunochemically assayed for soybean aeroallergen. On 31 separate days, the airborne allergen concentration in at least one of the samples was over 10000 U/m3 similar to those observed in Barcelona on some epidemic days. Areas North and East of the elevator were most affected. Serologie studies showed that of 50 asthmatics from New Orleans who were participants in an unrelated clinical study 4 or 8% demonstrated elevated titers of IgE antibody to LMM soybean allergen. Only 1 of 475 control sera (half of which were also asthmatic) obtained elsewhere in the US was positive for LMM soybean IgE antibody. Based on the findings in this study, there is a great possibility that on some days there is enough soybean allergen in the air and a sufficient frequency of soybean aeroallergen RAST positive asthmatics in New Orleans to warrant further investigation of the contribution of soybean aeroallergen to asthma around the port of New Orleans.

Many patients with esophageal cancer have advanced disease that is not amenable to curative treatment. For these individuals the relief of dysphagia is of utmost importance to the quality of their remaining survival time. This article reviews and compares the methods of palliation with focus on indications and contraindications, advantages as well as disadvantages of each technique, success rates, and complications. Tumor characteristics, the physician's experience, the institution's capabilities, cost, and patient preference will influence choice of palliation. Methods are often complementary rather than competitive.

This paper analyses the effects of the presence of Liberian refugees on cost of goods/services and business activities, pressure on resources/facilities, social vices and environmental activities based on perceptions (although attempts have been made to buttress the perceptions with information from focus group discussions) of hosts and refugees. The analysis included gender and type of occupation from within and among the groups. The aim was to ascertain whether the presence of refugees are viewed as having positive, negative or mixed impacts. Data are from 10 focus group discussions and 120 household surveys undertaken in April 2007. Results show that although there are gender and occupational differentials, host communities contend that refugees have increased the costs of goods and services, brought pressure on facilities, increased social vices and deteriorated environmental resources. However, refugees are viewed as a source of income and market, and trade partners, who have brought a lot of infrastructural developments. Thus, one can describe refugee presence as having mixed impacts.

We reviewed our experience with endoscopically evaluated severe upper gastrointestinal hemorrhage following open heart surgery. Of 4892 patients undergoing open heart surgery, 18 (0.4%) sustained upper gastrointestinal hemorrhage requiring endoscopic evaluation. Endoscopy identified the source of bleeding in all cases. No significant complications of endoscopy were observed. Duodenal ulcers (DUs) were found in 16 (89%) of cases and were felt to be the source of bleeding in 15 (83%). Aggressive features, such as multiplicity, large size, or distal location were associated with 13 (81%) of the DU cases. Complications necessitated endoscopic or surgical therapy in eight (44%) patients with DUs. We conclude that aggressive DU disease accounts for the majority of severe upper gastrointestinal bleeding following open heart surgery.

The pharmacokinetics of zopolrestat, a carboxylic acid aldose reductase inhibitor, were examined in normal male rats dosed intravenously at 2 mg/kg and in normal and streptozotocin-diabetic male rats after oral administration at 50 mg/kg. After oral dosing, Cmax was 127 µg/ml for normal rats and 144 µg/ml for diabetic rats. AUC(0–∞), however, was lower for diabetic rats than for normal rats and plasma half-life was longer in normal rats (8.0 vs 6.6 hr). Half-lives of zopolrestat in nerve, kidney, and lens were longer than plasma half-life and were similar for both diabetic and normal rats. Less than 2% of the dose was excreted in the urine as unchanged zopolrestat during the 48-hr period following dosing by diabetic or normal rats. Protein binding of zopolrestat was less extensive in plasma from diabetic rats than in plasma from normal rats. Similar kinetics were observed in diabetic animals receiving-five daily doses of zopolrestat at 50 mg/kg/day. There was no plasma or liver accumulation of zopolrestat at steady state, consistent with the observed half-lives. However, zopolrestat did accumulate in nerve, kidney, and lens to varying degrees during multiple dosing, reflecting the longer half-lives of zopolrestat in these tissues.