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The name of author Hans Oh was presented incorrectly as “By Hans Oh” in this article as original published.

The hostile environment of high temperature and CO2 pressure has limited previous Venus surface mission durations to less than 2 h giving only a glimpse of the Venus surface, despite the use of considerable insulation, phase-change materials, and similar heat sinks to isolate the payload and avionics from high surface temperatures. NASA has initiated studies to develop new power technologies that can tolerate the high Venus surface temperature of 465 °C and pressure of 92 bar, and operate for future long-duration Venus landers and probes. Such in-situ investigations are crucial to gather basic information on the crust, mantle, core, and bulk composition of Venus for understanding the evolutionary paths of Venus in relation to Earth. In this paper, we describe the development of high temperature primary batteries based on lithium alloy anodes, transition metal sulfide cathodes, and molten salt electrolytes. Among the various cathode materials examined for thermal stability and for electrochemical activity, FeS has emerged as the most suitable cathode. With optimized cell components, cell design, and operational parameters, laboratory test cells were fabricated, which demonstrated continuous operation of ~26 days at 475 °C. These batteries will enable new long-duration surface missions for detailed surface exploration of Venus.

The challenging environment of high temperature and high pressure on the Venus surface limit the battery options for Venus landers and surface probes. High temperature batteries employing Li alloy anodes, molten salt electrolytes and FeS cathodes were demonstrated to be resilient and operational for several days. For further improvements in performance, i.e., both specific energy and operational life, new high-capacity cathode materials are needed. Transition metal phosphorus trisulfides (TMPS3) are promising with considerably higher (2X) specific capacity, specific energy and energy density, by virtue of their ability to react with more than two lithium ions. This papers describes the assessment of these cathodes for high temperature batteries to power future Venus landers and probes. Manganese, iron, cobalt and nickel phosphorus trisulfides were synthesized and characterized by Scanning Electron Microscopy (SEM)/Energy Dispersive X-ray Spectroscopy (EDAX) and X-ray Diffraction (XRD) and tested in our high-temperature laboratory cells at 475 °C using cyclic voltammetry (CV) and galvanostatic discharges at different rates. Mn, Fe and Ni phosphorus trisulfides showed reversible behavior in cyclic voltammetric measurements. In the discharge tests, NiPS3 displayed the highest capacity out of the three metal phosphorous trisulfides tested at both C/20 and C/720 rates, with higher voltages and slightly higher capacity than FeS, followed by FePS3, while MnPS3 displayed relatively poor performance at C/20. Cathodes extracted from the discharged cells contain the transition metal (Fe, Ni or Mn) and Li2S by XRD, as expected from the reaction scheme.

Weather and climate influence multiple aspects of infectious disease ecology. Creating and applying early warning systems based on temperature, precipitation, and other environmental data can identify where and when outbreaks of climate-sensitive infectious diseases could occur and can be used by decision makers to allocate resources. Whether an outbreak actually occurs depends heavily on other social, political, and institutional factors. Improving the timing and confidence of seasonal climate forecasting, coupled with knowledge of exposure-response relationships, can identify prior conditions conducive to disease outbreaks weeks to months in advance of outbreaks. This information could then be used by public health professionals to improve surveillance in the most likely areas for threats. Early warning systems are well established for drought and famine. And while weather- and climate-driven early warning systems for certain diseases, such as dengue fever and cholera, are employed in some regions, this area of research is underdeveloped. Early warning systems based on temperature, precipitation, and other environmental data provide an opportunity for early detection leading to early action and response to potential pathogen threats, thereby reducing the burden of disease when compared with passive health indicator-based surveillance systems.

The pharmaceutical industry has continued to experience a large number of mergers, often involving the very largest companies. Behind many of these mergers has been the desire to achieve scale efficiencies and improved performance in both commercial and research and development (RD) activities.This research draws upon ClinicalTrials.gov data about commercially sponsored phase 3 clinical trials started and completed between 2008 and 2013. The research uses the bidirectional stepwise Akaike information criterion for model selection, adding a second-order term to the model where second-order terms were significant.First, and least surprising, the study therapeutic area has a major impact on study completion times. Second, the protocol design itself, as well as the clinical study execution plan, can have important consequences on study completion times. Several study execution variables are also critical to understanding completion times. While the size of clinical trial organization is not associated with more rapid completion times, the amount of organizational experience that an organization has in a particular therapeutic area does have a demonstrable impact. The models are able to supply the specific number of incremental completion days associated with each significant variable.Recent years have witnessed increasingly larger pharmaceutical RD organizations, as many companies have worked to achieve the scale benefits of organizational size for RD as well as commercial activity. Larger pharmaceutical companies may still achieve scale benefits. Faster phase 3 study completion times is not one of them.

This study uses the data from many of the mandatory fields in ClinicalTrials.gov to examine changes, possibly leading to more complexity in the design and execution of commercially sponsored phase 3 clinical trials.In this analysis we compare baseline year 2008 data, when a broad number of the protocol/study design and execution variables became mandatory, with the data from the last full year of results, 2013.There has been relatively little change in the protocol and study design over the years covered in this study. The most pronounced change is associated with single-patient duration: there is a significant increase in the period of time a patient is treated in the study protocol. The study also highlights an important methodological issue: many of the claims in print about complexity have yet been substantiated through the use of peer-reviewed data or in settings where others can interrogate the results.In general, there is limited evidence for significant increases in the study and protocol design and execution of phase 3 clinical trials sponsored by pharmaceutical companies.

UNSTRUCTURED Behavioral intervention technologies (BITs) are websites, software, mobile apps, and sensors designed to help users address or change behaviors, cognitions, and emotional states. BITs have the potential to transform health care delivery, and early research has produced promising findings of efficacy. BITs also favor new models of health care delivery and provide novel data sources for measurement. However, there are few examples of successful BIT implementation and a lack of consensus on as well as inadequate descriptions of BIT implementation measurement. The aim of this viewpoint paper is to provide an overview and characterization of implementation outcomes for the study of BIT use in routine practice settings. Eight outcomes for the evaluation of implementation have been previously described: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability. In a proposed recharacterization of these outcomes with respect to BIT implementation, definitions are clarified, expansions to the level of analysis are identified, and unique measurement characteristics are discussed. Differences between BIT development and implementation, an increased focus on consumer-level outcomes, the expansion of providers who support BIT use, and the blending of BITs with traditional health care services are specifically discussed. BITs have the potential to transform health care delivery. Realizing this potential, however, will hinge on high-quality research that consistently and accurately measures how well such technologies have been integrated into health services. This overview and characterization of implementation outcomes support BIT research by identifying and proposing solutions for key theoretical and practical measurement challenges.

Background Experts recommend that alcohol-related care be integrated into primary care (PC) to improve prevention and treatment of unhealthy alcohol use. However, few healthcare systems offer such integrated care. To address this gap, implementation researchers and clinical leaders at Kaiser Permanente Washington (KPWA) partnered to design a high-quality program of evidence-based care for unhealthy alcohol use: the Sustained Patient-centered Alcohol-related Care (SPARC) program. SPARC implements systems of clinical care designed to increase both prevention and treatment of unhealthy alcohol use. This clinical care for unhealthy alcohol use was implemented using three strategies: electronic health record (EHR) decision support, performance monitoring and feedback, and front-line support from external practice coaches with expertise in alcohol-related care (“SPARC implementation intervention” hereafter). The purpose of this report is to describe the protocol of the SPARC trial, a pragmatic, cluster-randomized, stepped-wedge implementation trial to evaluate whether the SPARC implementation intervention increased alcohol screening and brief alcohol counseling (so-called brief interventions), and diagnosis and treatment of alcohol use disorders (AUDs) in 22 KPWA PC clinics. Methods/Design The SPARC trial sample includes all adult patients who had a visit to any of the 22 primary care sites in the trial during the study period (January 1, 2015–July 31, 2018). The 22 sites were randomized to implement the SPARC program on different dates (in seven waves, approximately every 4 months). Primary outcomes are the proportion of patients with PC visits who (1) screen positive for unhealthy alcohol use and have documented brief interventions and (2) have a newly recognized AUD and subsequently initiate and engage in alcohol-related care. Main analyses compare the rates of these primary outcomes in the pre- and post-implementation periods, following recommended approaches for analyzing stepped-wedge trials. Qualitative analyses assess barriers and facilitators to implementation and required adaptations of implementation strategies. Discussion The SPARC trial is the first study to our knowledge to use an experimental design to test whether practice coaches with expertise in alcohol-related care, along with EHR clinical decision support and performance monitoring and feedback to sites, increase both preventive care—alcohol screening and brief intervention—as well as diagnosis and treatment of AUDs. Trial registration The trial is registered at ClinicalTrials.Gov: NCT02675777. Registered February 5, 2016, https://clinicaltrials.gov/ct2/show/NCT02675777. Electronic supplementary material The online version of this article (10.1186/s13012-018-0795-9) contains supplementary material, which is available to authorized users.

Cannabis is the third most commonly used drug in the USA, after alcohol and tobacco, and the prevalence of cannabis use and cannabis use disorders (CUD) has doubled in the last decade, due in part to increasingly legalized access.1,2 Individuals who use cannabis have increased risk of behavioral health conditions, including depression, anxiety, and tobacco, alcohol, and other substance use disorders,3–5 but little is known about the association between frequency of cannabis use and behavioral health conditions among primary care patients. This population-based study of primary care patients6 reports on the prevalence of common behavioral health conditions across cannabis use frequency.

The Open Payments database represents a new, substantial source of information on the US clinical trial investigator landscape.This paper draws upon the Open Payments database. This database, mandated by the US Sunshine Act, does help provide a vital missing element in understanding the commercial clinical trial landscape in the United States: comprehensive, detailed, clinical investigator and site information by specific clinical trial. Pharmaceutical companies are required to report all payment detail to US-based physicians, including their participation in US clinical trials. The data are available going back to the second half of 2013 and are updated each year. Data compliance is very high.Open Payments data demonstrate, consistent with ClinicalTrials.gov results, a constancy in the level of commercially sponsored clinical trial activity. The number of active clinical investigators for example has remained unchanged each year since 2013. The percentage of one-time investigators is substantially lower than has often been quoted. A strikingly large percentage of investigators in the United States though participate in a very limited number of clinical trials. A large majority of clinical investigators conduct clinical trials in their private practice.Following the US experience, other countries are instituting physician payment databases similar to Open Payments Open Payments provides critical management and operation data, including detailed investigator and site experience data. In addition, it is possible to estimate how investigators performed on each clinical trial.

Background Elderly patients presenting with a traumatic brain injury (TBI) often have comorbidities that increase risk of thromboembolic (TE) disease and recurrent TBI. A significant number are on anticoagulant therapy at the time of injury and studies suggest that continuing anticoagulation can prevent TE events. Understanding bleeding, recurrent TBI, and TE risk after TBI can help to guide therapy. Our objectives were to 1) evaluate the incidence of bleeding, recurrent TBI, and TE events after an initial TBI in older adults and 2) identify which factors contribute to this risk. Methods Retrospective analysis of Medicare claims between May 30, 2006 and December 31, 2009 for patients hospitalized with TBI was performed. We defined TBI for the index admission, and hemorrhage (gastrointestinal bleeding or hemorrhagic stroke), recurrent TBI, and TE events (stroke, myocardial infarction, deep venous thrombosis, or pulmonary embolism) over the following year using ICD-9 codes. Unadjusted incidence rates and 95% confidence intervals (CIs) were calculated. Risk factors of these events were identified using logistic regression. Results Among beneficiaries hospitalized with TBI, incidence of TE events (58.6 events/1000 person-years; 95% CI 56.2, 60.8) was significantly higher than bleeding (23.6 events/1000 person-years; 95% CI 22.2, 25.1) and recurrent TBI events (26.0 events/1000 person-years; 95% CI 24.5, 27.6). Several common factors predisposed to bleeding, recurrent TBI, and TE outcomes. Conclusions Among Medicare patients hospitalized with TBI, the incidence of TE was significantly higher than that of bleeding or recurrent TBI. Specific risk factors of bleeding and TE events were identified which may guide care of older adults after TBI.

A molecular imaging tool that provides for the direct visualization of serotonin would significantly aid in the investigation of neuropsychiatric disorders that are attributed to its neuronal dysregulation. Here, the design, synthesis, and evaluation of NeuroSensor 715 (NS715) is presented. NS715 is the first molecular sensor that exhibits a turn-on near-infrared fluorescence response toward serotonin. Density functional theory calculations facilitated the design of a fluorophore based on a coumarin-3-aldehyde scaffold that derives from an electron-rich 1,2,3,4-tetrahydroquinoxaline framework, which provides appropriate energetics to prevent the hydroxyindole moiety of serotonin from quenching its fluorescence emission. Spectroscopic studies revealed that NS715 produces an 8-fold fluorescence enhancement toward serotonin with an emission maximum at 715 nm. Accompanying binding studies indicated NS715 displays a 19-fold selective affinity for serotonin and a modest affinity for catecholamines over other primary-amine neurotransmitters. The utility of NS715 toward neuroimaging applications was validated by selectively labeling and directly imaging norepinephrine within secretory vesicles using live chromaffin cells, which serve as a model system for specialized neurons that synthesize, package, and release only a single, unique type of neurotransmitter. In addition, NS715 effectively differentiated between cell populations that express distinct neurotransmitter phenotypes.

Hemoglobin E is largely confined to south and southeast Asia. The association between hemoglobin E (HbE) and malaria is less clear than that of hemoglobin S and C. As part of a malaria study in the Chittagong Hill Districts of Bangladesh, an initial random sample of 202 individuals showed that 39% and 49% of Marma and Khyang ethnic groups, respectively, were positive for either heterozygous or homozygous hemoglobin E. In this group, 6.4% were also found to be severely deficient and 35% mildly deficient for glucose-6-phosphate dehydrogenase (G6PD). In a separate Plasmodium falciparum malaria case–uninfected control study, the odds of having homozygous hemoglobin E (HbEE) compared with normal hemoglobin (HbAA) were higher among malaria cases detected by passive surveillance than age and location matched uninfected controls (odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.07–46.93). The odds of heterozygous hemoglobin E (HbAE) compared with HbAA were similar between malaria cases and uninfected controls (OR = 0.71, 95% CI = 0.42–1.19). No association by hemoglobin type was found in the initial parasite density or the proportion parasite negative after 2 days of artemether/lumefantrine treatment. HbEE, but not HbAE status was associated with increased passive case detection of malaria.

Introduction Alcohol use disorder symptoms frequently occur in adolescents and younger adults who seldom acknowledge a need for help. We identified sociodemographic, clinical, and familial predictors of alcohol problem recognition and help seeking in an offspring of twin sample. Method We analyzed longitudinal data from the Children of Alcoholics and Twins as Parents studies, which are combinable longitudinal data sources due to their equivalent design. We analyzed respondents ( n = 1073, 56.0% of the total sample) with alcohol use disorder symptoms at the baseline interview. Familial characteristics included perceptions of alcohol problems and help seeking for alcohol problems within the immediate family and a categorical variable indicating genetic and environmental risk. We used logistic regression to examine predictors of alcohol problem recognition and help seeking. Results Approximately 25.9% recognized their alcohol problems and 26.7% sought help for drinking. In covariate-adjusted analyses, help seeking among family members predicted problem recognition, several clinical characteristics predicted both problem recognition and help seeking, and familial risk predicted help seeking. Alcohol problem recognition mediated the association between alcohol use disorder symptoms and incident help seeking. Conclusions Facilitating the self-recognition of alcohol use disorder symptoms, and perhaps the awareness of family members’ help seeking for alcohol problems, may be potentially promising methods to facilitate help seeking.

Background The objective of this study was to characterize variations in packed red blood cell (PRBC) transfusion practices in critically ill patients and to identify which factors influence such practices. We hypothesized that significant variation in transfusion triggers exists among acute care surgeons. Methods A survey of PRBC transfusion practices was administered to the American Association for the Surgery of Trauma members. The scenarios examined hemoglobin thresholds for which participants would transfuse PRBCs. Results A hemoglobin threshold of less than or equal to 7 g/dL was adopted by 45% of respondents in gastrointestinal bleeding, 75% in penetrating trauma, 66% in sepsis, and 62% in blunt trauma. Acute care surgeons modified their transfusion trigger significantly in the majority of the modifications of these scenarios, often inappropriately so. Conclusions This study documents continued evidence-practice gaps and wide variations in the PRBC transfusion practices of acute care surgeons. Numerous clinical factors altered such patterns despite a lack of supporting evidence (for or against).

People who obtain treatment for alcohol use problems often utilize multiple sources of help. While prior studies have classified treatment use patterns for alcohol use, an empirical classification of these patterns is lacking. For the current study, we created an empirically derived classification of treatment use and described how these classifications were prospectively associated with alcohol-related outcomes. Our sample included 257 participants of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who first received alcohol treatment in the 3-year period prior to their baseline interview. We used latent class analysis to identify classes of treatment users based on their patterns of treatment use of 13 types of alcohol treatment. Regression models examined how classes of treatment use at baseline were associated with alcohol-related outcomes assessed at a 3-year follow-up interview. Outcomes included a continuous measure of the quantity and frequency of alcohol use and DSM-IV alcohol use disorder status. Four classes of treatment users were identified: (1) multiservice users (8.7%), (2) private professional service users (32.8%), (3) alcoholics anonymous (AA) paired with specialty addiction service users (22.0%), and (4) users of AA alone (36.5%). Those who utilized AA paired with specialty addiction services had better outcomes compared to those who used AA alone. In addition to elucidating the most common treatment utilization patterns executed by people seeking help for their alcohol problems, the results from this study suggest that increased efforts may be needed to refer individuals across sectors of care to improve treatment outcomes.

Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis.

Rattus norvegicus (Norway rat) is one of the most abundant and geographically widespread mammals. Ecological studies focusing on urban Norway rat populations are restricted to temperate regions, and data describing populations from tropical cities are lacking. We compared the morphometrics and demographic characteristics of rats captured in urban low-income settlements in Salvador, Brazil, to a season, environmental area of capture, and sex-matched sample from Baltimore, Maryland. Norway rats of both sexes were significantly smaller in Salvador, although the threshold mass marking sexual maturity was equivalent for both cities. Pregnancy rates were comparable (~50%); however, juveniles were commonly trapped in Salvador (20%) while they were rarely trapped in Baltimore during winter months (2%). These findings suggest that tropical and temperate rats differ with respect to body metrics, while size at sexual maturity is similar. Further studies conducted over different seasons are required before any firm conclusions are reached; however, this study provides preliminary support for Bergmann’s rule that species at higher absolute latitude are larger than the same species sampled at lower latitudes.

Since 2007, the US federal government has required that organizations sponsoring clinical trials with a least one site in the United States submit information on these clinical trials to an existing database: ClinicalTrials.gov . Over time, the number of mandatory variables has grown and will probably continue to grow. The database now represents an important source of descriptive information about the landscape for clinical trials. In addition, it constitutes a rich pool of data to test hypotheses-for instance, what variables are associated with an organization's ability to correctly estimate study completion times or complete those studies in as short a time frame as possible. This paper concludes that for mandated variables that the authors have labeled study identification, protocol and study design, and study execution, the data set constitutes a potentially very valuable research resource. With the exception of some site-related information, incomplete data did not exceed 3%. The incomplete site data are concentrated in several companies, so it is not unreasonable to assume that those data will also become more complete.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.

Introduction Necrotising soft tissue infection (NSTI) is a rare but life threatening diagnosis. Geographic, economic and social variances influence presentation and prognosis. As the current literature does not reflect a UK metropolitan population, we conducted a retrospective chart review to establish pertinent features relevant to our practice. Methods Patients with histologically confirmed diagnoses of NSTI presenting to two London teaching hospitals between January 2007 and July 2013 were included in the study. Features of presentation, surgical and medical management, microbiological findings and outcome were evaluated. Results Twenty-four patients with histologically confirmed NSTI were included. Two age clusters were identified, with means of 46 years (standard deviation [SD]: 10 years) and 80 years (SD: 6 years). Pain, erythema and sepsis were common findings. Hypertension, hypercholesterolaemia and type II diabetes mellitus were common co-morbidities. A third of younger patients had human immunodeficiency virus or hepatitis C, with a quarter dependent on drugs and/or alcohol. The mean Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score was 5.8 (SD: 3.3). The lower extremities, groin and perineum were common sites of infection. Fourteen patients required inotropic support and seventeen required transfusions. The median number of surgical procedures was 5 (range: 1–17). Group A Streptococcus was the most frequently identified pathogen. Five patients died. Being elderly, female sex and failure to use clindamycin as a first-line antibiotic were associated with significantly higher mortality. Conclusions In contrast to other recent series, group A streptococcal monomicrobial NSTI remains the most common presentation in our population. Survival is anticipated in young patients, regardless of premorbid status. Elderly patients have a poor prognosis. The negative predictive value of the LRINEC score is questioned. Use of clindamycin as a first-line antibiotic is supported.

Pelvic fractures can lead to life-threatening hemorrhage, particularly as they tend to occur in the setting of polytrauma. Several approaches to hemorrhage control have been employed in pelvic fracture patients over the years. This review describes the indications, operative technique, and outcomes for preperitoneal pelvic packing (PPP). Pelvic packing should be considered for every hemodynamically unstable patient with a significant pelvic fracture. We describe how this can be accomplished in coordination with other resuscitative efforts and operative needs.

Little is known regarding patterns of alcohol use and alcohol-related care among transgender adults. This study examined alcohol use and alcohol-related care across transgender status in a probability sample of U.S. adults.We conducted secondary analyses of the 2014 Behavioral Risk Factor Surveillance System survey, focusing on adults in eight states that administered both an Alcohol Screening and Brief Intervention module and a Gender Identity module (n = 58,381). Measurements included transgender status, sociodemographic characteristics, alcohol consumption (any alcohol use, risky drinking, heavy episodic drinking, and any unhealthy alcohol use), and alcohol-related care (alcohol screening during healthcare visits and advice about unhealthy alcohol use). We tested the association between transgender status and alcohol consumption and alcohol-related care using multivariable logistic regression models adjusted for sociodemographic characteristics.Approximately 0.6% of respondents (n = 283) self-identified as transgender. Overall, there were no significant differences in alcohol consumption or screening between transgender and nontransgender adults. A greater proportion of transgender than nontransgender adults reported being advised to reduce alcohol use (20.7% vs. 7.8%, p = .012). However, this difference was not significant after adjusting for other sociodemographic characteristics (adjusted odds ratio = 2.31, 95% CI [0.91, 5.86], p = .077).In this representative sample from eight U.S. states, we did not find differences related to transgender status in rates of alcohol use or of alcohol-related care.

Coronary artery bypass graft (CABG) operations are associated with all-cause readmission rates of approximately 15%. In attempts to reduce readmission rates, the Hospital Readmission Reduction Program expanded to include CABG operations in 2015. The aim of this study was therefore to develop a predictive readmission scale that would identify patients at higher risk of readmission after CABG using commonly available administrative data.Data of 126,519 patients from California and New York (derivation cohort) and 94,318 patients from Florida and Washington (validation cohort) were abstracted from the State Inpatient Database (2006 to 2011). The readmission after CABG scale was developed to predict 30-day readmission risk and was validated against a separate cohort.Thirty-day CABG readmission rates were 23% in the derivation cohort and 21% in the validation cohort. Predictive factors included older age, female gender (odds ratio [OR], 1.34), African American ethnicity (OR, 1.13), Medicare or Medicaid insurance, and comorbidities, including renal failure (OR, 1.56) and congestive heart failure (OR, 2.82). These were independently predictive of increased readmission rates (p0.01). The readmission scale was then created with these preoperative factors. When applied to the validation cohort, it explained 98% of the readmission variability.The readmission after CABG scale reliably predicts a patient's 30-day CABG readmission risk. By identifying patients at high-risk for readmission before their procedure, risk reduction strategies can be implemented to reduce readmissions and healthcare expenditures.

Despite efforts to control Lyme disease in Connecticut, USA, it remains endemic in many towns, posing a heavy burden. We examined changes in the spatial distribution of significant spatial clusters of Lyme disease incidence rates at the town level from 1991 to 2014 as an approach for targeted interventions. Lyme disease data were grouped into four discrete time periods and incidence rates were smoothed with Empirical Bayes estimation in GeoDa. Local clustering was measured using a local indicator of spatial autocorrelation (LISA). Elliptic spatial scan statistics (SSS) in different shapes and directions were also performed in SaTScan. The accuracy of these two cluster detection methods was assessed and compared for sensitivity, specificity, and overall accuracy. There was significant clustering during each period and significant clusters persisted predominantly in western and eastern parts of the state. Generally, the SSS method was more sensitive, while LISA was more specific with higher overall accuracy in identifying clusters. Even though the location of clusters changed over time, some towns were persistently (across all four periods) identified as clusters in LISA and their neighbouring towns (three of four periods) in SSS suggesting these regions should be prioritized for targeted interventions.

In 2016, the International Network on Brief Interventions for Alcohol & Other Drugs convened a meeting titled "Rethinking alcohol interventions in health care". The aims of the meeting were to synthesize recent evidence about screening and brief intervention and to set directions for research, practice, and policy in light of this evidence. Screening and brief intervention is efficacious in reducing self-reported alcohol consumption for some with unhealthy alcohol use, but there are gaps in evidence for its effectiveness. Because screening and brief intervention is not known to be efficacious for individuals with more severe unhealthy alcohol use, recent data showing the lack of evidence for referral to treatment as part of screening and brief intervention are alarming. While screening and brief intervention was designed to be a population-based approach, its reach is limited. Implementation in real world care also remains a challenge. This report summarizes practice, research, and policy recommendations and key research developments from our meeting. In order to move the field forward, a research agenda was proposed to (1) address evidence gaps in screening, brief intervention, and referral to treatment, (2) develop innovations to address severe unhealthy alcohol use within primary care, (3) describe the stigma of unhealthy alcohol use, which obstructs progress in prevention and treatment, (4) reconsider existing conceptualizations of unhealthy alcohol use that may influence health care, and (5) identify efforts needed to improve the capacity for addressing unhealthy alcohol consumption in all world regions.

Background Opioid addiction and overdose are epidemic in the U.S. Victims of traumatic injury are at greater than average risk for opioid misuse and related complications. Potential risk screens and preventive interventions in this clinical population remain under-investigated. The current project seeks to develop and pilot the implementation of a screening tool for opioid risk at American College of Surgeons (ACS) Level I and Level II trauma centers. Methods The project began with an online survey, which was sent to Wisconsin trauma center medical directors and trauma coordinators for the purpose of gathering information on current substance use screening practices. Next, a focus group of trauma center staff was convened to discuss barriers and facilitators to screening, resources available and needed to support trauma patients with opioid use disorders, and measurable clinical observations that could indicate a patient’s potential risk for opioid misuse. Data from the surveys and focus group were combined to inform the data collection instruments that are currently being administered to patients recruited from the University of Wisconsin Hospital Trauma Inpatient and Orthopedic Surgery Services. Eligible and consenting patients complete standardized measures of socio-demographics, substance use history, opioid misuse risk, mental health, medical history, and injury and pain severity. Follow up visits at weeks 4, 12, and 24 after hospital discharge assess hypothesized risk factors for opioid addiction and opioid use disorder diagnosis. At the completion of patient data collection, a forward stepwise regression will identify factors of most significant risk of the development of opioid use disorder after traumatic injury. This modeling will inform the development of a novel opioid risk screening tool, which will undergo pilot implementation at 4 Wisconsin ACS Level I and Level II trauma centers, using an evidence-based implementation strategy with roots in systems engineering. Discussion Positive findings from the proposed work would lead to improved, standardized opioid risk screening practices among victims of traumatic injury. The ultimate goal of this and future work is to reduce the likelihood of opioid misuse, addiction, and related complications, such as overdose and death. Trial registration Clinicaltrials.gov registration number: NCT02861976. Date of registration: Feb 9, 2016

In our recently published paper (1), we find evidence that several metrics of socioeconomic status were associated with influenza and pneumonia mortality during the 1918 pandemic. We agree with Shanks and Brundage (2) that there are many possible causal mechanisms behind this association and appreciate the hypotheses that they add to the several we discussed. Secondary bacterial infections, particularly those secondary bacterial infections resulting in pneumonia, have been implicated in a number of deaths during the 1918 pandemic period (3⇓–5). Our dataset includes deaths attributed both to … [↵][1]1To whom correspondence should be addressed. Email: datc{at}ufl.edu. [1]: #xref-corresp-1-1

Spring-assisted cranioplasty has been proposed as an alternative to total calvarial remodeling for sagittal craniosynostosis. Advantages include its minimally invasive nature, and reduced morbidity and hospital stay. Potential drawbacks include the need for a second procedure for removal and the lack of published long-term follow-up. The authors present a single-institution experience of 100 consecutive cases using a novel spring design.All patients treated at the authors' institution between April of 2010 and September of 2014 were evaluated retrospectively. Patients with isolated nonsyndromic sagittal craniosynostosis were included. Data were collected for operative time, anesthetic time, hospital stay, transfusion requirement, and complications in addition to cephalic index preoperatively and at 1 day, 3 weeks, and 6 months postoperatively.One hundred patients were included. Mean cephalic index was 68 preoperatively, 71 at day 1, and 72 at 3 weeks and 6 months postoperatively. Nine patients required transfusion. Two patients developed a cerebrospinal fluid leak requiring intervention. One patient required early removal of springs because of infection. One patient had a wound dehiscence over the spring and one patient sustained a venous infarct with hemiplegia. Five patients required further calvarial remodeling surgery.The authors' modified spring design and protocol represents an effective strategy in the management of single-suture sagittal craniosynostosis with reduced total operative time and blood loss compared with alternative treatment strategies. In patients referred within the first 6 months of birth, this technique has become the authors' procedure of choice. In a minority of cases, especially in the older age groups, further remodeling surgery is required.Therapeutic, IV.

Pharmacologic treatment is recommended for alcohol use disorders (AUD), but most patients do not receive it. Although racial/ethnic minorities have greater AUD consequences than whites, whether AUD medication receipt varies across race/ethnicity is unknown. We evaluate this in a national sample.Electronic health records data were extracted for all black, Hispanic, and/or white patients who received care at the U.S. Veterans Health Administration (VA) during Fiscal Year 2012 and had a documented AUD diagnosis. Mixed effects regression models, with a random effect for facility, determined the likelihood of receiving AUD pharmacotherapy (acamprosate, disulfiram, topirimate or oral or injectable naltrexone ≤180days after AUD diagnosis) for black and Hispanic patients relative to white patients. Models were unadjusted and then adjusted for patient- and facility-level factors.297,506 patients had AUD; 26.4% were black patients, 7.1% were Hispanic patients and 66.5% were white patients; 5.1% received AUD medications. Before adjustment, black patients were less likely than white [Odds Ratio (OR) 0.77; 95% Confidence Interval (CI) 0.75 -0.82; (p0.001)], while Hispanic patients were more likely than white (OR 1.09; 95% CI 1.01-1.16) to receive AUD medications. After adjustment, black patients remained less likely than white to receive AUD medications (OR 0.68; 95% CI 0.65-0.71; p0.0001); no difference between Hispanic and white patients was observed (OR 0.94; 95% CI 0.87-1.00; p=0.07).In this national study of patients with AUD, blacks were less likely to receive AUD medications than whites. Future research is needed to identify why these disparities exist.

Passive drag devices provide opportunities to return payloads from low Earth orbits quickly without using onboard propulsive systems to de-orbit the spacecraft. However, one potential disadvantage of such systems has been the lack of landing accuracy. Drag modulation or changing the shape of the drag device during flight offer a way to control the de-orbit trajectory and target a specific landing location. This paper discusses a candidate passive drag based system, called Exo-brake, as well as efforts to model the dynamics of the vehicle as it de-orbits and guidance schemes used to control the trajectory. Such systems can enable quick return of payloads from low Earth orbit assets like the International Space Station without the use of large re-entry cargo capsules or propulsive systems.

Amines are an important class of molecules that are ubiquitous in biology, pharmaceuticals, and industry. Here, we explore the properties of amines, the reversible binding strategies, and the molecular scaffolds that have been utilized for fluorescence sensing. Several signal transduction mechanisms can be used to turn the fluorescence “on” or “off,” such as acceptor- or donor-excited photoinduced electron transfer and internal charge transfer. The scaffolds range in complexity from small molecules and organometallic complexes to polymers and molecular containers (e.g., tweezers and tubes).

The advancement of supramolecular chemistry has led to an explosion in the development of chemical sensors. The ability to detect chemical entities is immensely important to many fields, including biology, medicine, engineering, and all aspects of modern technology. In particular, fluorescent sensors and probes have become the premier method to explore analytes in biological systems. This volume covers all aspects of fluorescent sensing and probe design with an emphasis on the supramolecular aspects of the work.

NeuroSensor 521 (NS521) is a fluorescent sensor for primary-amine neurotransmitters based on a platform that consists of an aryl moiety appended to position C4 of the coumarin-3-aldehyde scaffold. We demonstrate that sensors based on this platform behave as a directly linked donor-acceptor system that operates through an intramolecular acceptor-excited photoinduced electron transfer (a-PET) mechanism. To evaluate the PET process, a series of benzene- and thiophene-substituted derivatives were prepared and the photophysical properties, binding affinities, and fluorescence responses toward glutamate, norepinephrine, and dopamine were determined. The calculated energy of the highest occupied molecular orbital (EHOMO ) of the pendant aryl substituents, along with oxidation and reduction potential values derived from the calculated molecular orbital energy values of the platform components, allowed for calculation of the fluorescence properties of the benzene sensor series. Interestingly, the thiophene derivatives did not fit the typical PET model, highlighting the limitations of the method. A new sensor, NeuroSensor 539, displayed enhanced photophysical properties aptly suited for biological imaging. NeuroSensor 539 was validated by selectively labeling and imaging norepinephrine in secretory vesicles of live chromaffin cells.

Background Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level. Methods MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively. Results Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1β was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor β and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1. Conclusion Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.

Spontaneous idiopathic facial nerve (Bell's) palsy leaves residual hemifacial weakness in 29% which is severe and disfiguring in over half of these cases. Acute medical management remains the best way to improve outcomes. Reconstructive surgery can improve long term disfigurement. However, acute and surgical options are time-dependent. As family practitioners see, on average, one case every 2 years, a summary of this condition based on common clinical questions may improve acute management and guide referral for those who need specialist input. We formulated a series of clinical questions likely to be of use to family practitioners on encountering this condition and sought evidence from the literature to answer them. The lifetime risk is 1 in 60, and is more common in pregnancy and diabetes mellitus. Patients often present with facial pain or paraesthesia, altered taste and intolerance to loud noise in addition to facial droop. It is probably caused by ischaemic compression of the facial nerve within the meatal segment of the facial canal probably as a result of viral inflammation. When given early, high dose corticosteroids can improve outcomes. Neither antiviral therapy nor other adjuvant therapies are supported by evidence. As the facial muscles remain viable re-innervation targets for up to 2 years, late referrals require more complex reconstructions. Early recognition, steroid therapy and early referral for facial reanimation (when the diagnosis is secure) are important features of good management when encountering these complex cases.

Malaria is endemic in the Chittagong Hill Districts of southeastern Bangladesh. Previous epidemiological analyses identified the agricultural practice of jhum cultivation as a potential risk factor for malaria infection. We conducted qualitative interviews with jhum cultivators and surveillance workers to describe jhum cultivation and used demographic and malaria surveillance in two study unions from May of 2010 to August of 2012 to better understand the relationship between jhum cultivation and malaria infection. Qualitative interviews revealed that jhum cultivation is conducted on remote, steep hillsides by ethnic tribal groups. Quantitative analyses found that adult jhum cultivators and individuals who live in the same residence had significantly higher incidence rates of symptomatic Plasmodium falciparum infection compared with non-cultivators. These results confirm that jhum cultivation is an independent risk factor for malaria infection and underscore the need for malaria testing and treatment services to reach remote populations in the Chittagong Hill Districts.

Road safety constitutes a crisis with important health and economic impacts. In 2010, 11,000 pedestrians and 3500 bicyclists were injured by motor vehicles in New York City (NYC). Motor vehicle injuries represent the second leading cause of injury-related deaths in NYC children aged 5 to 14 years. To better target injury prevention strategies, we evaluated demographics, behaviors, environmental factors, injuries, and outcomes of pediatric pedestrians and bicyclists struck by motor vehicles in NYC.Pediatric data were extracted from a prospectively collected database of pedestrians and bicyclists struck by motor vehicles and treated at a level I regional trauma center between December 2008 and June 2011. Patients, guardians, and first responders were interviewed and medical records were reviewed. Institutional review board approval was granted and verbal consent was obtained.Of the 1457 patients, 168 (12%) were younger than 18 years. Compared with injured adults, children were more likely to be in male sex (69% vs 53%), to have minor injuries (83% vs 73% for injury severity scores of9), and to be discharged without admission (69% vs 67%). Midblock crossings were more common in children pedestrians than in adults (37% vs 19%), often despite supervision (48%). Electronic device use among teenagers aged 13 to 17 years was nearly 3 times that of adults (28% vs 11%).Risky behaviors are common among pediatric pedestrians and bicyclists injured by motor vehicles. Road safety education and prevention strategies must stress compliance with traffic laws, readdress the importance of supervision, and reinforce avoidance of common distractors including electronic devices.

SummaryObjective: To identify the severity of neurological deficits, presence of signs of cervical pain, and the site of intervertebral disc space extrusion in 21 dogs diagnosed via magnetic resonance imaging (MRI) with a hydrated nucleus pulposus extrusion (HNPE) and compare those findings to dogs with other compressive cervical myelopathies.Methods: Medical records and MRI findings were reviewed in dogs that were presented to two veterinary hospitals between 2006 and 2012 and subsequently diagnosed by MRI to have a HNPE (n = 21) or other compressive cervical myelopathies originating from the intervertebral disc (n = 174). Information obtained included signalment, severity of neurological deficits, presence of signs of neck pain, and site of HNPE. The severity of clinical neurological spinal cord dysfunction was determined for each dog in both groups using the Frankel scoring system (0–4). The MRI were reviewed for confirmation of diagnosis and site of HNPE. An ANOVA was used to compare age between groups and a Mann-Whitney test for pairwise comparisons of the Frankel score between groups. Values of p Results: Significantly more severe Frankel scores and less severe signs of cervical pain detected on palpation were observed in dogs with a HNPE as compared to dogs with other compressive myelopathies. The sites of HNPE were C3-C4 (8/21), C4-C5 (12/21), and C5-C6 (1/21).Clinical significance: Dogs affected with HNPE have more severe clinical neurological deficits and less severe signs of cervical pain as compared to dogs with other compressive cervical myelopathies.