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Objective: To understand which social, epidemiologic, and clinical risk factors are associated with SARS-CoV-2 infection in youth accessing care in a large, urban academic institution. Methods: We conducted a prospective cohort study with case-control analyses in youth who received testing for SARS-CoV-2 at our academic institution in Los Angeles during the first wave of the COVID-19 pandemic (March-September 2020). Results: A total of 27,976 SARS-CoV-2 assays among 11,922 youth aged 0-24 years were performed, including 475 youth with positive SARS-CoV-2 results. Positivity rate was higher among older, African American, and Hispanic/Latinx youth. Cases were more likely to be from non-English-speaking households and have safety-net insurance. Zip codes with higher proportion of Hispanic/Latinx and residents living under the poverty line were associated with increased SARS-CoV-2 cases. Youth were more likely to have positive results if tested for exposure (OR 21.5, 95% CI 14.6-32.1) or recent travel (OR 1.5, 95% CI 1.0-2.3). Students were less likely to have positive results than essential worker youth (OR 0.5, 95% CI 0.3-0.8). Patterns of symptom presentation varied significantly by age group; number of symptoms correlated significantly with age in SARS-CoV-2 cases ( r = 0.030, p < 0.001). SARS-CoV-2 viral load did not vary by symptom severity, but asymptomatic youth had lower median viral load than those with symptoms (21.5 vs. 26.7, p = 0.009). Conclusions: Socioeconomic factors are important drivers of SARS-CoV-2 infection in youth. Presence of symptoms, exposure, and travel can be used to drive testing in older youth. Policies for school reopening and infection prevention should be tailored differently for elementary schools and universities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Newhouse, Saleh, Fuller, Kerin, Cambou, Swayze, Le, Seo, Trejo, Garner, Chandrasekaran and Nielsen-Saines.)

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks., Competing Interests: J.U.J. is a scientific adviser to Vaccine Stabilization, a California corporation., (© 2021 The Author(s).)

Due to intense ongoing urbanization in the Amazon, the urban pattern of malaria may be changing, both in its spatial distribution and epidemiological profile. The purpose of this paper is to analyze how the process of production of urban space in Porto Velho, the capital of the state of Rondonia, Brazil has contributed to the occurrence and maintenance of urban malaria. Using data collected from the Malaria Epidemiological Surveillance System (SIVEP-Malaria), we calculated malaria indices for the districts of Porto Velho from 2005 to 2018. We also developed two typologies for classifying urban space based on functional characteristics and features of the landscape. While the former considers characteristics of urban space in Porto Velho, the latter is based on suitability for malaria vectors. We found that the annual parasite index declined in Porto Velho during the study period. However, changes in the index were not uniform across the districts of the city. Periurban areas showed no decline in the index, which we attribute to these areas' high vegetation density and hydrological characteristics.

While the annual incidence of HIV diagnosis in pregnancy in Brazil remains relatively stable, rates of maternal syphilis increased over six-fold in the past decade. We hypothesized that maternal HIV and syphilis are two distinct epidemics. Data on all cases of maternal HIV or syphilis detected in pregnancy between January 1, 2010 to December 31, 2018 were requested from the Brazilian Ministry of Health. In order to evaluate how the epidemics evolved over the time period, ArcGIS software was used to generate spatiotemporal maps of annual rates of detection of maternal HIV and syphilis in 2010 and 2018. We utilized Euclidean-distance hot spot analysis to identify state-specific clusters in 2010 and 2018. From 2010 to 2018, there were 66,631 cases of maternal HIV, 225,451 cases of maternal syphilis, and 150,414 cases of congenital syphilis in Brazil. The state of Rio Grande do Sul had the highest rate of maternal HIV detection in both 2010 and 2018. Hot spots of maternal HIV were identified in the three most Southern states in both 2010 and 2018 (99% confidence, z-score >2.58, p <0.01). While syphilis incidence >30 per 1,000 live births in 2018 in four states, only the two coastal states of Rio de Janeiro and Espirito Santo in Southeastern Brazil were significant hot spots (90% confidence, z-score 1.65-1.95, p <0.10). Contrary to the general assumption, HIV and syphilis epidemics in Brazil are not syndemic in pregnant women. There is a spatial cluster of maternal HIV in the South, while syphilis is increasing throughout the country, more recently on the coast. Focusing on maternal HIV hot spots in the Southern states is insufficient to curtail the maternal and congenital syphilis epidemics throughout the country. New strategies, including ongoing hot spot analysis, are urgently needed to monitor, identify and treat maternal syphilis., Competing Interests: The authors have declared that no competing interests exist.

VanLee is a singleton phage that was isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540 as the host. The genome is 84,560 bp and has a GC content of 67.8%. VanLee has 164 predicted protein-coding genes and one tRNA. VanLee can infect Gordonia terrae with the same efficiency as G. rubripertincta.

Objectives: To investigate the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vulnerable population of children and their household contacts., Methods: SARS-CoV-2 reverse transcription polymerase chain reaction assays and coronavirus disease 2019 (COVID-19) immunoglobulin G serology tests were performed in children and their household contacts after enrollment during primary health care clinic visits. Participants were followed prospectively with subsequent specimens collected through household visits in Manguinhos, an impoverished urban slum (a favela) in Rio de Janeiro at 1, 2, and 4 weeks and quarterly post study enrollment., Results: Six hundred sixty-seven participants from 259 households were enrolled from May to September 2020. This included 323 children (0-13 years), 54 adolescents (14-19 years), and 290 adults. Forty-five (13.9%) children had positive test results for SARS-CoV-2 polymerase chain reaction. SARS-CoV-2 infection was most frequent in children aged <1 year (25%) and children aged 11 to 13 years (21%). No child had severe COVID-19 symptoms. Asymptomatic infection was more prevalent in children aged <14 years than in those aged ≥14 years (74.3% and 51.1%, respectively). All children ( n = 45) diagnosed with SARS-CoV-2 infection had an adult contact with evidence of recent infection., Conclusions: In our setting, children do not seem to be the source of SARS-CoV-2 infection and most frequently acquire the virus from adults. Our findings suggest that, in settings such as ours, schools and child care potentially may be reopened safely if adequate COVID-19 mitigation measures are in place and staff are appropriately immunized., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Purpose: GSK2982772 is a selective inhibitor of receptor-interacting protein kinase-1, with a 2-3 h half-life. This study evaluated if a once-daily modified-release formulation of GSK2982772 could be developed with no significant food effect., Methods: Part A evaluated the pharmacokinetics of GSK2982772 following fasted single-dose (120 mg) administration of two matrix minitab formulations (MT-8 h and MT-12 h) vs 120 mg immediate release (IR) and MT-12 h with a high-fat meal. Part B evaluated once-daily MT-12 h for 3 days at three dose levels. Part C evaluated a matrix monolithic (MM-12 h) formulation at two dose levels in different prandial states., Results: All modified-release formulations dosed in the fasted state reduced maximum plasma concentration (Cmax), delayed time to C max , and decreased area under the curve (AUC) vs IR. When MT-12 h or MM-12 h were co-administered with a meal (standard or high-fat) C max and AUC increased. Dosing MM-12 h 1 h before a standard or high-fat meal had minimal impact on exposure vs fasted., Conclusions: MT-12 h and MM-12 h provided a QD pharmacokinetic profile in the fasted state, however when MT-12 h was dosed with a high-fat meal a QD profile was not maintained. ( ClinicalTrials.gov Identifier: NCT03266172)., (© 2021. The Author(s).)

There are some reports and case series addressing Coronavirus Disease 2019 (COVID-19) infections during pregnancy in upper income countries, but there are few data on pregnant women with comorbid conditions in low and middle income Countries. This study evaluated the proportion and the maternal and neonatal outcomes associated with SARS-CoV-2 infection among pregnant women with comorbidities. Participants were recruited consecutively in order of admission to a maternity for pregnant women with comorbidities. Sociodemographic, clinical, and laboratory data were prospectively collected during hospitalization. Pregnant women were screened at entry: nasopharyngeal swabs were tested by RT-PCR; serum samples were tested for IgG antibodies against spike protein by ELISA. From April to June 2020, 115 eligible women were included in the study. The proportion of SARS-CoV-2 infection was 28.7%. The rate of obesity was 60.9%, vascular hypertension 40.0%, and HIV 21.7%. The most common clinical presentations were ageusia (21.2%), anosmia (18.2%), and fever (18.2%). Prematurity was higher among mothers who had a SARS-CoV-2 infection based on RT-PCR. There were two cases of fetal demise. We found a high proportion of COVID-19 among pregnant women with comorbidities. This underscores the importance of antenatal care during the pandemic to implement universal SARS-CoV-2 screening, precautionary measures, and the rollout of vaccination programs for pregnant women.

With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August-24 November of 2019). We sampled wildlife at 1,509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the United States. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as will future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication., (© 2021 The Authors. Ecology © 2021 The Ecological Society of America.)

Objectives: To assess non-invasive imaging for detection and quantification of gland structure, inflammation and function in patients with primary Sjogren's syndrome (pSS) using PET-CT with 11C-Methionine (11C-MET; radiolabelled amino acid), and 18F-fluorodeoxyglucose (18F-FDG; glucose uptake marker), to assess protein synthesis and inflammation, respectively; multiparametric MRI evaluated salivary gland structural and physiological changes., Methods: In this imaging/clinical/histology comparative study (GSK study 203818; NCT02899377) patients with pSS and age- and sex-matched healthy volunteers underwent MRI of the salivary glands and 11C-MET PET-CT. Patients also underwent 18F-FDG PET-CT and labial salivary gland biopsies. Clinical and biomarker assessments were performed. Primary endpoints were semi-quantitative parameters of 11C-MET and 18F-FDG uptake in submandibular and parotid salivary glands and quantitative MRI measures of structure and inflammation. Clinical and minor salivary gland histological parameter correlations were explored., Results: Twelve patients with pSS and 13 healthy volunteers were included. Lower 11C-MET uptake in parotid, submandibular and lacrimal glands, lower submandibular gland volume, higher MRI fat fraction, and lower pure diffusion in parotid and submandibular glands were observed in patients vs healthy volunteer, consistent with reduced synthetic function. Disease duration correlated positively with fat fraction and negatively with 11C-MET and 18F-FDG uptake, consistent with impaired function, inflammation and fatty replacement over time. Lacrimal gland 11C-MET uptake positively correlated with tear flow in patients, and parotid gland 18F-FDG uptake positively correlated with salivary gland CD20+ B-cell infiltration., Conclusion: Molecular imaging and MRI may be useful tools to non-invasively assess loss of glandular function, increased glandular inflammation and fat accumulation in pSS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The Zika virus (ZIKV) epidemic in Brazil occurred in regions where dengue viruses (DENV) are historically endemic. We investigated the differences in adverse pregnancy/infant outcomes in two cohorts comprising 114 pregnant women with PCR-confirmed ZIKV infection in Rio de Janeiro, Southeastern Brazil ( n = 50) and Manaus, in the north region of the country ( n = 64). Prior exposure to DENV was evaluated through plaque reduction neutralizing antibody assays (PRNT 80) and DENV IgG serologies. Potential associations between pregnancy outcomes and Zika attack rates in the two cities were explored. Overall, 31 women (27%) had adverse pregnancy/infant outcomes, 27 in Rio (54%) and 4 in Manaus (6%), p < 0.001. This included 4 pregnancy losses (13%) and 27 infants with abnormalities at birth (24%). A total of 93 women (82%) had evidence of prior DENV exposure, 45 in Rio (90%) and 48 in Manaus (75%). Zika attack rates differed; the rate in Rio was 10.28 cases/10,000 and in Manaus, 0.6 cases/10,000, p < 0.001. Only Zika attack rates (Odds Ratio: 17.6, 95% Confidence Interval 5.6-55.9, p < 0.001) and infection in the first trimester of pregnancy (OR: 4.26, 95% CI 1.4-12.9, p = 0.011) were associated with adverse pregnancy and infant outcomes. Pre-existing immunity to DENV was not associated with outcomes (normal or abnormal) in patients with ZIKV infection during pregnancy.

Despite the investment in prevention of mother-to-child transmission of HIV, there is still little data about the proportion of women that are retained in treatment after pregnancy in Brazil. Research worldwide shows that a significant proportion of women drop out of treatment after pregnancy. The aim of this study was to identify factors associated with treatment dropout of women that received prenatal care at a federal hospital in Rio de Janeiro between 2016 and 2017 and abandoned treatment after pregnancy. This was a retrospective cohort study using data on prescription refills and hospital medical records. Cross-sectional analysis of data from 454 women showed that 18% were not on cART after pregnancy. Illicit drug use during pregnancy, being less than 35 years old, and being aware of HIV diagnosis before conceiving but not taking cART were factors associated with treatment interruption postpartum. The high prevalence of interruption of HIV treatment after pregnancy suggests that there is a need for better post-natal care to increase adherence in this population.

A positive and expected by-product of a well-programmed instructional sequence is an escalation of learning, where skills are acquired more quickly as teaching goes on. Despite the importance of this effect in behavior analysis and education, techniques for detecting and analyzing it are rarely observed in practice settings. A behavioral approach to this phenomenon is rooted in the term agility , which has persisted in the precision-teaching community as a description of desirable acquisition patterns. Precision teachers have long carried forward a loose definition of agility as "celerating celerations." Although this definition might succeed in generally orienting practitioners toward the goal of helping people acquire new skills more quickly, its lack of technical specificity has hindered efforts to fully integrate such analyses into practice. In this article, the authors define agility and distinguish it from other concepts common to education and behavior analysis. Further, a tutorial for quantifying and analyzing agility using frequency, celeration, and bounce multipliers is presented in detail. Finally, the practical implications afforded by analyses of agility are delineated., Competing Interests: Conflict of InterestAll authors declare they have no conflicts of interest., (© The Author(s) 2020.)

Purpose: To assess efficacy of intravitreal ranibizumab injections and targeted panretinal photocoagulation (TRP) for radiation retinopathy-related macular edema., Design: Phase IIb, prospective, randomized clinical trial., Methods: Setting: Multicenter., Subjects: Forty eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen equivalent)., Intervention: Patients either received intravitreal 0.5 mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MainOutcomeMeasures: Mean Early Treatment Diabetic Maculopathy Study (ETDRS) BCVA change from baseline., Results: Mean patient age was 57 years (range, 22-80 years), ETDRS BCVA was 56.7 letters (20/74 Snellen equivalent), and central macular thickness (CMT) was 423 μm (range, 183-826 μm). Thirty-seven patients completed the month 12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters, and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all 3 cohorts (P < .001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. A total of 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters., Conclusions: Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Predicting species' capacity to respond to climate change is an essential first step in developing effective conservation strategies. However, conservation prioritization schemes rarely take evolutionary potential into account. Ecotones provide important opportunities for diversifying selection and may thus constitute reservoirs of standing variation, increasing the capacity for future adaptation. Here, we map patterns of environmentally associated genomic and craniometric variation in the central African rodent Praomys misonnei to identify areas with the greatest turnover in genomic composition. We also project patterns of environmentally associated genomic variation under future climate change scenarios to determine where populations may be under the greatest pressure to adapt. While precipitation gradients influence both genomic and craniometric variation, vegetation structure is also an important determinant of craniometric variation. Areas of elevated environmentally associated genomic and craniometric variation overlap with zones of rapid ecological transition underlining their importance as reservoirs of evolutionary potential. We also find that populations in the Sanaga river basin, central Cameroon and coastal Gabon are likely to be under the greatest pressure from climate change. Lastly, we make specific conservation recommendations on how to protect zones of high evolutionary potential and identify areas where populations may be the most susceptible to climate change.

Introduction: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre., Patients and Methods: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1 /pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014. Pre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews., Results: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4 % of patients died during follow-up. 4.7 % and 8.4 % developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results., Discussion: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes., Competing Interests: Die Autoren geben an, dass keine Interessenskonflikte bestehen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus., Objectives: To assess the effects and safety of CBT for tinnitus in adults., Search Methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019., Selection Criteria: Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome., Main Results: We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points lower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal communication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves health-related quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects., Authors' Conclusions: CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT for tinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, health-related quality of life or negatively biased interpretations of tinnitus., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Until recently, advances in understanding the genetic architecture of psychiatric disorders have been impeded by a historic, and often mandated, commitment to the use of traditional, and unvalidated, categorical diagnoses in isolation as the relevant phenotype. Such studies typically required lengthy structured interviews to delineate differences in the character and duration of behavioral symptomatology amongst disorders that were thought to be etiologic, and they were often underpowered as a result. Increasing acceptance of the fact that co-morbidity in psychiatric disorders is the rule rather than the exception has led to alternative designs in which shared dimensional symptomatology is analyzed as a quantitative trait and to association analyses in which combined polygenic risk scores are computationally compared across multiple traditional categorical diagnoses to identify both distinct and unique genetic and environmental elements. Increasing evidence that most mental disorders share many common genetic risk variants and environmental risk modifiers suggests that the broad spectrum of psychiatric pathology represents the pleiotropic display of a more limited series of pathologic events in neuronal development than was originally believed, regulated by many common risk variants and a smaller number of rare ones., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

We established a Patient Safety Learning Laboratory comprising 2 core and 3 individual project teams to introduce a suite of digital health tools integrated with our electronic health record to identify, assess, and mitigate threats to patient safety in real time. One of the core teams employed systems engineering (SE) and human factors (HF) methods to analyze problems, design and develop improvements to intervention components, support implementation, and evaluate the system of systems as an integrated whole. Of the 29 participants, 19 and 16 participated in surveys and focus groups, respectively, about their perception of SE and HF. We identified 7 themes regarding use of the 12 SE and HF methods over the 4-year project. Qualitative methods (interviews, focus, groups, observations, usability testing) were most frequently used, typically by individual project teams, and generated the most insight. Quantitative methods (failure mode and effects analysis, simulation modeling) typically were used by the SE and HF core team but generated variable insight. A decentralized project structure led to challenges using these SE and HF methods at the project and systems level. We offer recommendations and insights for using SE and HF to support digital health patient safety initiatives., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus., Method: Here we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This 'European School for Interdisciplinary Tinnitus Research Screening Questionnaire' (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration., Conclusions: With respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: At our residency program, incoming interns are traditionally taught fundamental open surgical skills like suturing and knot tying in a group setting by viewing 12 instructional videos consecutively followed by individual baseline skill testing. We sought to evaluate if introduction to open surgical skills via self-paced viewing of video tutorials, as opposed to traditional group viewing, results in improved surgical skill acquisition in Obstetrics and Gynecology (OBGYN) interns as measured by higher proficiency score with decreased workload stress and anxiety., Design, Setting, Participants: A randomized control trial was conducted in which OBGYN PGY-1 residents in 2015 and 2016 (N = 35) were introduced to basic open surgical skills, such as knot tying and suturing, by viewing 12 video tutorials produced at UTSW (https://youtu.be/4w3hyL9muVU) for a surgical skills curriculum. Residents were randomized to 2 groups: group viewing vs self-paced viewing. Performance scores were calculated based on time and accuracy while workload and anxiety were measured by preand post-testing surveys using the National Aeronautics and Space Administration-Task Load Index and Spielberger State-Trait Anxiety Inventory 6 item questionnaires., Results: There was no significant difference in proficiency score between the group vs self-paced viewing in 8 out of 12 tasks using the Wilcoxon signed rank test (p > 0.10). There was no statistically significant differences in workload stress based on the National Aeronautics and Space Administration-Task Load Index questionnaire (p = 0.399) or self-reported anxiety based on the Spielberger State-Trait Anxiety Inventory 6 item questionnaire (p = 0.607)., Conclusions: Contrary to recent educational data suggesting self-paced learning may improve outcomes, viewing instructional videos in a group setting continues to be a time efficient method to introduce basic open surgical skills to incoming OBGYN interns., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

The study aim was to investigate the pharmacokinetics of single high doses and repeated therapeutic doses of fluticasone furoate (FF) and batefenterol (BAT; a bifunctional muscarinic antagonist and β 2 -agonist) administered in combination (BAT/FF) or as monotherapy. In this open-label, 6-period, crossover study of 48 subjects, the treatment sequences were (1) single high-dose BAT/FF 900/300 μg followed by repeated therapeutic doses of BAT/FF 300/100 μg (once daily for 7 days); (2) single high-dose BAT 900 μg administered concurrently with FF 300 μg; (3) single high-dose BAT 900 μg followed by repeated therapeutic-dose BAT 300 μg; (4) single high-dose FF 300 μg followed by repeated therapeutic-dose FF 100 μg; (5) single high-dose FF 300 μg (magnesium stearate); and (6) single high-dose FF/vilanterol 300/75 μg. Plasma FF area under the plasma drug concentration-time curve (AUC) was reduced after single high-dose BAT/FF versus FF alone (ratio of geometric least squares means: 0.79; 90% confidence interval: 0.75-0.83). After repeat dosing, FF AUC at the lower therapeutic dosage was similar for BAT/FF and FF (primary endpoint; AUC geometric least squares means: 1.03). Adverse events were minor, the most common being cough. These data support the feasibility of developing BAT/inhaled corticosteroid triple therapy in a single inhaler., (© 2018, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.)

Inhaled batefenterol is an investigational bifunctional molecule for the treatment of chronic obstructive pulmonary disease. The excretion balance and pharmacokinetics of batefenterol using [ 14 C]-radiolabeled drug administered orally and as intravenous (IV) infusion were assessed. In this 2-period, open-label study, 6 healthy male subjects received a single IV microtracer 1-hour infusion of 4 μg [ 14 C]-batefenterol concomitant with inhaled nonradiolabeled batefenterol (1200 μg) followed by oral [ 14 C]-batefenterol (200 μg) in period 2 after a 14-day washout. The primary end points included: the area under the concentration-time curve from time zero to last time of quantifiable concentration (AUC 0-t ); maximum observed concentration (C max ); and time of occurrence of maximum observed concentration. Following IV administration, the geometric mean AUC 0-t of [ 14 C]-batefenterol was 121.9 pgEq • h/mL; maximum observed concentration and time of occurrence of maximum observed concentration were 92.7 pgEq/mL and 0.8 hours, respectively; absolute oral bioavailability was 0.012%. The mean AUC 0-t ratio indicated that [ 14 C]-batefenterol accounted for 85% of total circulating radioactivity in the plasma initially and declined rapidly following IV administration, but only ∼0.2% of total circulating radioactivity following oral administration. Cumulative mean recovery of total radioactive [ 14 C]-batefenterol in urine and feces was 6.31% and 77.6%, respectively. Overall, batefenterol exhibited low systemic bioavailability after inhaled and oral administration, and high fecal excretion and low urinary excretion following IV and oral administration., (© 2018, The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.)

Recent outbreaks of Ebola virus disease and Zika virus disease highlight the need for disseminating accurate predictions of emerging zoonotic viruses to national governments for disease surveillance and response. Although there are published maps for many emerging zoonotic viruses, it is unknown if there is agreement among different models or if they are concordant with national expert opinion. Therefore, we reviewed existing predictions for five high priority emerging zoonotic viruses with national experts in Cameroon to investigate these issues and determine how to make predictions more useful for national policymakers. Predictive maps relied primarily on environmental parameters and species distribution models. Rift Valley fever virus and Crimean-Congo hemorrhagic fever virus predictions differed from national expert opinion, potentially because of local livestock movements. Our findings reveal that involving national experts could elicit additional data to improve predictions of emerging pathogens as well as help repackage predictions for policymakers.

As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-cell ALL; however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL. We demonstrate that blasts from patients with T-ALL have robust surface CD38 surface expression and that this expression remains stable after exposure to multiagent chemotherapy. CD38 is expressed at very low levels on normal lymphoid and myeloid cells and on a few tissues of nonhematopoietic origin, suggesting that CD38 may be an ideal target. Daratumumab is a human immunoglobulin G1κ monoclonal antibody that binds CD38, and has been demonstrated to be safe and effective in patients with refractory multiple myeloma. We tested daratumumab in a large panel of T-ALL patient-derived xenografts (PDX) and found striking efficacy in 14 of 15 different PDX. These data suggest that daratumumab is a promising novel therapy for pediatric T-ALL patients., (© 2018 by The American Society of Hematology.)

Background/objectives: Processed foods are considered major contributors to the worldwide obesity epidemic. In addition to high sugar and fat contents, processed foods contain large amounts of salt. Owing to the correlations with rising adiposity, salt has recently been proposed to be obesogenic. This study investigated three hypotheses: (i) high salt contributes to weight gain and adiposity in juvenile female rats, (ii) puberty onset would be altered because salt is known to affect neuronal systems involved in activating the reproductive system, and (iii) enhanced adiposity will act synergistically with salt to drive early puberty onset., Design: Female weanling rats (post-natal day 21, n=105) were fed a low fat/low salt diet, low fat/high salt diet, high fat/low salt diet or a high salt/high fat diet for 24 days. Metabolic measures, including weight gain, food intake, fecal output, activity and temperature were recorded in subsets of animals., Results: Body weight, retroperitoneal and perirenal fat pad weight, and adipocyte size were all lower in animals fed high fat/high salt compared with animals fed high fat alone. Leptin levels were reduced in high fat/high salt fed animals compared with high fat/low salt-fed animals. Daily calorie intake was higher initially but declined with adjusted food intake and was not different among groups after 5 days. Osmolality and corticosterone were not different among groups. Fecal analysis showed excess fat excretion and a decreased digestive efficiency in animals fed high fat/low salt but not in animals fed high fat/high salt. Although respiratory exchange ratio was reduced by high dietary fat or salt, aerobic-resting metabolic rate was not affected by the diet. High salt delayed puberty onset, regardless of dietary fat content., Conclusions: Salt delays puberty and prevents the obesogenic effect of a high fat diet. The reduced weight gain evident in high salt-fed animals is not due to differences in food intake or digestive efficiency.

Despite decades of debate about the most effective ways to intervene with families reported to child protective services (CPS), little evidence exists regarding the types of services or approach that reduce children's risk of additional maltreatment. The current study used data collected during a statewide experimental evaluation of CPS to examine the impact of numerous service variables, family engagement, and family characteristics on the risk of maltreatment re-reports and substantiated re-reports among families initially reported for neglect and risk of harm. The sample included 4,868 families with screened-in reports that were randomly assigned to receive either an investigation or an assessment. The results of the Cox regression analyses found that service duration, intensity, and breadth were unrelated to maltreatment re-report or substantiated re-reports, but caseworker ratings of the service-need match were associated with both. The provision of domestic violence services was related to decreased risk of maltreatment re-reports. Increased levels of family engagement were associated with lowered risk of both maltreatment re-reports and substantiated re-reports. Once the effects of services, engagement, and family characteristics were taken into account, CPS response pathway (investigation or assessment) had no relationship to maltreatment re-reports or substantiated re-reports.

A patient safety plan dashboard was developed that captures disparate data from the electronic health record that is then displayed as a personalized bedside screensaver. The dashboard aligns all care team members, including patients and families, in the safety plan. The screensaver content includes icons that pertain to common geriatric syndromes. In two phases, interviews were conducted with nurses, nursing assistants, patients, and informal caregivers in a large, tertiary care center. End user perceptions of the content and interface of the personalized safety plan screensavers were identified and strategies to overcome the barriers to use for future iterations were defined. Many themes were identified, ranging from appreciation of the clinical decision support provided by the screensavers to the value of the safety-centric content. Differences emerged stemming from each group of end users' role on the care team. All feedback will inform requirements for improvements to the personalized safety plan screensaver. [Journal of Gerontological Nursing, 43(4), 15-22.]., (Copyright 2017, SLACK Incorporated.)

Next generation sequence data were generated and used to assemble the complete plastomes of the holotype of Membranoptera weeksiae, the neotype (designated here) of M. tenuis, and a specimen examined by Kylin in making the new combination M. platyphylla. The three plastomes were similar in gene content and length and showed high gene synteny to Calliarthron, Grateloupia, Sporolithon, and Vertebrata. Sequence variation in the plastome coding regions were 0.89% between M. weeksiae and M. tenuis, 5.14% between M. weeksiae and M. platyphylla, and 5.18% between M. tenuis and M. platyphylla. We were unable to decipher the complete mitogenomes of the three species due to low coverage and structural problems; however, we assembled and analyzed, the cytochrome oxidase I, II, and III loci and found that M. weeksiae and M. tenuis differed in sequence by 1.3%, M. weeksiae and M. platyphylla by 8.4%, and M. tenuis and M. platyphylla by 8.1%. Evaluation of standard marker genes indicated that sequences from the rbcL, RuBisCO spacer, and CO1 genes closely approximated the pair-wise genetic distances observed between the plastomes of the three species of Membranoptera. A phylogenetic tree based on rbcL sequences showed that M. tenuis and M. weeksiae were sister taxa. Short rbcL sequences were obtained from type specimens of M. dimorpha, M. multiramosa, and M. edentata and confirmed their conspecificity with M. platyphylla. The data support the recognition of three species of Membranoptera occurring south of Alaska: M. platyphylla, M. tenuis, and M. weeksiae., (© 2016 Phycological Society of America.)

Purpose: To evaluate the specific spectral-domain (SD) optical coherence tomography (OCT) features of retinal astrocytic hamartoma (RAH) and the relationship of these features with tumor size and location., Design: Retrospective case series., Participants: Forty-seven eyes of 42 patients with RAH., Methods: All patients with clinically confirmed RAH were imaged with fundus photography and SD OCT., Main Outcome Measures: Precise OCT location of RAH features and the relationship of patient age, visual acuity, tumor size, and tumor location to the presence and size of intralesional optically empty spaces (OESs), appearing as so-called moth-eaten spaces., Results: Of 42 patients with RAH, 36 (86%) had unilateral disease and 6 (14%) had bilateral disease. Systemic tuberous sclerosis complex was present in 8 patients (19%). The largest tumor (per eye) demonstrated a mean basal diameter of 3.0 mm (median, 2.0 mm) and a mean thickness of 1.9 mm (median, 1.8 mm). The mean tumor proximity to the foveola was 3.0 mm and that to the optic disc was 1.8 mm. Related features included subretinal fluid (n = 9; 19%), cystoid retinal edema (n = 6; 13%), retinal traction (n = 11; 23%), intralesional cavities (n = 28; 60%), and intralesional calcification (n = 29; 62%). On SD OCT, the tumor epicenter was in the nerve fiber layer (n = 47; 100%), with all other retinal layers appearing thinned or compressed. The tumor showed OESs (n = 43; 91%), representing intralesional calcification or cavitation, and each OES showed a mean diameter of 327 μm (median, 200 μm). When comparing the number of OESs per SD OCT cut through the mass, we found no relationship with patient age, tumor diameter and thickness, distance to the foveola or optic disc, tumor calcification, central macular thickness, or logarithm of the minimum angle of resolution (logMAR) visual acuity. However, a correlation of OES number with OES size (P = 0.01) and macular tumor location (P = 0.03) was found. Further analysis demonstrated OES size correlated with tumor basal diameter (P < 0.01), tumor thickness (P < 0.01), tumor calcification (P = 0.01), and logMAR visual acuity (P = 0.02)., Conclusions: Retinal astrocytic hamartomas arose in the nerve fiber layer in every case and demonstrated moth-eaten OES, related to intrinsic calcification or cavitation, in 91% of cases. Macular tumors have a greater number of OESs, whereas larger calcified tumors have larger OES diameter., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus., Methods: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded., Results: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used., Conclusions: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments., Prospero Registration: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Purpose: The purpose of this study was to describe and compare the rates and characteristics of noninfectious vitritis after intravitreal injection of bevacizumab (Avastin, Genentech, South San Francisco, CA), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron, Tarrytown, NY)., Methods: A retrospective case series evaluated intravitreal injections from 2006 to 2013. Cases of inflammatory response were separated into culture-positive endophthalmitis, noninfectious vitritis (not treated with intravitreal antibiotics), and indeterminate. Noninfectious cases were analyzed for rate, presentation, and clinical course., Results: A total of 66,356 bevacizumab, 26,161 ranibizumab, and 8071 aflibercept injections were screened. The rates of noninfectious vitritis were 0.10% (67 cases) for bevacizumab, 0.02% (6 cases) for ranibizumab, and 0.16% (13 cases) for aflibercept. The differences were statistically significant based on Chi-square analysis (P < 0.001). Mean differences in visual decline were not significant by Kruskal-Wallis analysis (P = 0.12), but the percentage of patients with any visual decline did vary by medication according to Fisher exact test (P < 0.05). The percentage of patients with complaints of pain, blurred vision, and subjective floaters was not significantly different by medication based on Fisher exact testing (P = 0.2, P = 0.18, P = 0.16, respectively). Bevacizumab and aflibercept cases tended to present in separate chronological clusters., Conclusion: The results suggest a difference in rates of noninfectious vitritis for antivascular endothelial growth factor medications. Many cases tended to cluster instead of occurring at a consistent rate each year.

We present the case of an infant who suffered intraperitoneal bladder perforation secondary to routine neonatal circumcision with the Plastibell device. On day-of-life 5, the patient presented with abdominal distention, vomiting, diarrhea, and severe acute renal failure. After removal of a distal meatal obstruction caused by the Plastibell device and open repair of the bladder defect, the patient had an uneventful recovery with rapid return of renal function. Despite the relative safety of the Plastibell, this case underscores the importance of careful device placement, parental education, keen clinical judgment, and prompt intervention when indicated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Avian influenza virus (AIV) is an important zoonotic pathogen, resulting in global human morbidity and mortality and substantial economic losses to the poultry industry. Poultry and wild birds have transmitted AIV to humans, most frequently subtypes H5 and H7, but also different strains and subtypes of H6, H9, and H10. Determining which birds are AIV reservoirs can help identify human populations that have a high risk of infection with these viruses due to occupational or recreational exposure to the reservoir species. To assess the prevalence of AIV in tropical birds, from 2010 to 2014, we sampled 40 099 birds at 32 sites in Central Africa (Cameroon, Central African Republic, Congo-Brazzaville, Gabon) and West Africa (Benin, Côte d'Ivoire, Togo). In Central Africa, detection rates by real-time RT-PCR were 16·6% in songbirds (eight passerine families, n = 1257), 16·4% in kingfishers (family Alcedinidae, n = 73), 8·2% in ducks (family Anatidae, n = 564), and 3·65% in chickens (family Phasianidae, n = 1042). Public health authorities should educate human cohorts that have high exposure to these bird populations about AIV and assess their adherence to biosecurity practices, including Cameroonian farmers who raise small backyard flocks.

Objectives: To identify and understand, through data from multiple sources, some of the factors that affect authors' and editors' decisions to use reporting guidelines in the publication of health research., Design: Mixed methods study comprising an online survey and semi-structured interviews with a sample of authors (online survey: n = 56; response rate = 32%; semi-structured interviews: n = 5) and journal editors (online survey: n = 43; response rate = 27%; semi-structured interviews: n = 6) involved in publishing health and medical research. Participants were recruited from an earlier study examining the effectiveness of the TREND reporting guideline., Results: Four types of factors interacted to affect authors' and editors' likelihood of reporting guideline use; individual (e.g., having multiple reasons for use of reporting guidelines); the professional culture in which people work; environmental (e.g., policies of journals); and, practical (e.g., having time to use reporting guidelines). Having multiple reasons for using reporting guidelines was a particularly salient factor in facilitating reporting guidelines use for both groups of participants., Conclusions: Improving the completeness and consistency of reporting of research studies is critical to the integrity and synthesis of health research. The use of reporting guidelines offers one potentially efficient and effective means for achieving this, but decisions to use (or not use) reporting guidelines take many factors into account. These findings could be used to inform future studies that might, for example, test the factors that we have identified within a wider theoretical framework for understanding changes in professional practices. The use of reporting guidelines by senior professionals appears to shape the expectations of what constitutes best practice and can be assimilated into the culture of a field or discipline. Without evidence of effectiveness of reporting guidelines, and sustained, multifaceted efforts to improve reporting, little progress seems likely to be made.

Minimizing adhesion of ice has been the subject of extensive studies because of importance to applications such aircraft wings, spacecraft, and power transmission wires. A growing interest concerns coatings for wind turbine blades and refrigeration. Herein, a new laboratory test was employed to obtain the thickness dependence of ice adhesion for Sylgard 184-a filled polydimethylsiloxane elastomer. A correlation between ice adhesion and coating thickness (t) was found that follows a relationship developed by Kendall over 40 years ago for removal of a rigid object from an elastomer. With a 0.05 mm/s probe speed a nearly linear relationship between peak removal stress (Ps) and 1/t(1/2) was obtained with Ps ∼ 460 kPa for an 18 μm coating, decreasing to ∼120 kPa for 533 μm. Preliminary results suggest that below ∼10 μm Ps departs from the 1/t(1/2) correlation while above ∼500 μm a limiting value for Ps may be reached. We previously reported that probe speed has negligible effect on the glassy polymer PMMA. In contrast, probe speed is identified as an important variable for testing ice release on elastomeric Sylgard 184 coatings. While work of adhesion, which is related to surface free energy, is recognized as an important factor that can affect ice release, the results reported herein show that coating thickness can override this single parameter for elastomeric substrates.

Objectives: We assessed how the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) reporting guideline was used by authors and journal editors in journals' instructions to authors. We also evaluated its impact on reporting completeness and study quality., Methods: We extracted data from publications that cited TREND on how TREND was used in those reports; we also extracted information on journals' instructions to authors. We then undertook a case-control study of relevant publications to evaluate the impact of using TREND., Results: Between 2004 and 2013, TREND was cited 412 times, but it was only evidently applied to study reports 47 times. TREND was specifically mentioned 14 times in the sample of 61 instructions to authors. Some evidence suggested that use of TREND was associated with more comprehensive reporting and higher study quality ratings., Conclusions: TREND appeared to be underutilized by authors and journal editors despite its potential application and benefits. We found evidence that suggested that using TREND could contribute to more transparent and complete study reports. Even when authors reported using TREND, reporting completeness was still suboptimal.

Historic rates of habitat change and growing exploitation of natural resources threaten avian biodiversity in the Brazilian Atlantic Forest, a global biodiversity hotspot. We implemented a twostage framework for conservation planning in the Atlantic Forest. First, we used ecological niche modeling to predict the distributions of 23 endemic bird species using 19 climatic metrics and 12 spectral and radar remote sensing metrics. Second, we utilized the principle of complementarity to prioritize new sites to augment the Atlantic Forest's existing reserves. The best predictors of bird distributions were precipitation metrics (the seasonality of rainfall) and radar remote sensing metrics (QSCAT). The existing protected areas do not include 10% of the habitat of each of the 23 endemic species. We propose a more economical set of protected areas by reducing the extent to which new sites duplicate the biodiversity content of existing protected areas. There is a high concordance between the proposed conservation areas that we designed using computerized algorithms and Important Bird Areas prioritized by BirdLife International. Insofar as deforestation in the Atlantic Forest is similar to land conversion in other biodiversity hotspots, our methodology is applicable to conservation efforts elsewhere in the world.

Objectives: The rapid emergence, spread, and disease severity of avian influenza A (H7N9) in China has prompted concerns about a possible pandemic and regional spread in the coming months. The objective of this study was to predict the risk of future human infections with H7N9 in China and neighboring countries by assessing the association between H7N9 cases at sentinel hospitals and putative agricultural, climatic, and demographic risk factors., Methods: This cross-sectional study used the locations of H7N9 cases and negative cases from China's influenza-like illness surveillance network. After identifying H7N9 risk factors with logistic regression, we used Geographic Information Systems (GIS) to construct predictive maps of H7N9 risk across Asia., Results: Live bird market density was associated with human H7N9 infections reported in China from March-May 2013. Based on these cases, our model accurately predicted the virus' spread into Guangxi autonomous region in February 2014. Outside China, we find there is a high risk that the virus will spread to northern Vietnam, due to the import of poultry from China., Conclusions: Our risk map can focus efforts to improve surveillance in poultry and humans, which may facilitate early identification and treatment of human cases., (Copyright © 2014 The British Infection Association. All rights reserved.)

Background: The 2009 pH1N1 influenza pandemic resulted in at least 18,500 deaths worldwide. While pH1N1 is now considered to be in a post-pandemic stage in humans it has nevertheless spilled back into swine in at least 20 countries. Understanding the factors that increase the risk of spillover events between swine and humans is essential to predicting and preventing future outbreaks. We assessed risk factors that may have led to spillover of pH1N1 from humans to swine in Cameroon, Central Africa. We sampled swine, domestic poultry and wild birds for influenza A virus at twelve sites in Cameroon from December 2009 while the pandemic was ongoing, to August 2012. At the same time we conducted point-count surveys to assess the abundance of domestic livestock and wild birds and assess interspecific contact rates. Random forest models were used to assess which variables were the best predictors of influenza in swine., Results: We found swine with either active pH1N1 infections or positive for influenza A at four of our 12 sites. Only one swine tested positive by competitive ELISA in 2011-2012. To date we have found pH1N1 only in the North and Extreme North regions of Cameroon (regions in Cameroon are administrative units similar to provinces), though half of our sites are in the Central and Western regions. Swine husbandry practices differ between the North and Extreme North regions where it is common practice in to let swine roam freely, and the Central and Western regions where swine are typically confined to pens. Random forest analyses revealed that the three best predictors of the presence of pH1N1 in swine were contact rates between free-ranging swine and domestic ducks, contact rates between free-ranging swine and wild Columbiformes, and contact rates between humans and ducks. Sites in which swine were allowed to range freely had closer contact with other species than did sites in which swine were kept penned., Conclusions: Results suggest that the practice of allowing swine to roam freely is a significant risk factor for spillover of influenza from humans into swine populations.

Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified.

Background: In elderly and multimorbid patients urosepsis is a particularly serious condition with a high mortality. Whether a secondary therapy for an underlying stone disease after -initial sepsis treatment improves the prognosis of these patients has not been systematically investigated. We retrospectively reviewed the clinical course of elderly and multimorbid patients with urosepsis regarding the frequency of rhospitalisation and sepsis recurrence after initial and subsequent therapy., Patients and Methods: Patients with and without urolithiasis and urosepsis were compared. Inclusion criteria were multimorbidity, defined by an ASA score (≥2) or a Charlson score (≥3) and age (≥60 years), and general sepsis features. Both groups (patients with urolithiasis [U+] and patients without urolithiasis [U-]) did not differ in terms of demographic data. We investigated the influence of the primary sepsis therapy and secondary stone treatment on the incidence of rehospitalisation and sepsis recurrence rate., Results: The incidence of rehospitalisation in stone patients (U+) with and without therapy did not differ (22.1% vs. 21%), while the occurrence of urosepsis was lower in treated patients (0% vs. 8.7%). Rehospitalisation in stone patients was generally less common than in patients without urolithiasis (U+ 21.6%, U- 44.4%). Recurrences of sepsis were higher in patients without stone disease (U+ 4.35%, U- 8.9%). If the subpopulation with successful stone therapy was extracted from the U+ group, the difference disappeared (U+ 8.7%, U- 8.9%)., Conclusions: Stone treatment after initial urosepsis therapy reduces the incidence of recurrent sepsis (0% vs. 8.7%). Patients without underlying urolithiasis (U-) have a similar risk of sepsis recurrence as urolithiasis patients without secondary stone treatment. A complete stone clearance should be pursued in multimorbid or elderly patients with urosepsis to reduce secondary morbidity., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Lymphocytes achieve diversity in antigen recognition in part by rearranging genomic DNA at loci encoding antibodies and cell surface receptors. The process, termed V(D)J recombination, juxtaposes modular coding sequences for antigen binding. Erroneous recombination events causing chromosomal translocations are recognized causes of lymphoid malignancies. Here we show a hybridization based method for sequence enrichment can be used to efficiently and selectively capture genomic DNA adjacent to V(D)J recombination breakpoints for massively parallel sequencing. The approach obviates the need for PCR amplification of recombined sequences., Results: Using tailored informatics analyses to resolve alignment and assembly issues in these repetitive regions, we were able to detect numerous recombination events across a panel of cancer cell lines and primary lymphoid tumors, and an EBV transformed lymphoblast line. With reassembly, breakpoints could be defined to single base pair resolution. The observed events consist of canonical V(D)J or V-J rearrangements, non-canonical rearrangements, and putatively oncogenic reciprocal chromosome translocations. We validated non-canonical and chromosome translocation junctions by PCR and Sanger sequencing. The translocations involved the MYC and BCL-2 loci, and activation of these was consistent with histopathologic features of the respective B-cell tumors. We also show an impressive prevalence of novel erroneous V-V recombination events at sites not incorporated with other downstream coding segments., Conclusions: Our results demonstrate the ability of next generation sequencing to describe human V(D)J recombinase activity and provide a scalable means to chronicle off-target, unexpressed, and non-amplifiable recombinations occurring in the development of lymphoid cancers.

Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4(th) Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.

Habituation has recently been addressed within the operant conditioning paradigm. While the literature on this topic is growing, the examination of dishabituation, a fundamental characteristic of habituation, remains limited. This study expanded research on habituation of operant responding in non-human animals to research involving humans. Specifically, dishabituation and stimulus specificity were examined under a variety of conditions involving changes in the reinforcer type, reinforcement schedule, reinforcer amount, and selected properties of the antecedent stimuli for a computerized task with 46 undergraduate students. An additional 3 participants were exposed to a control condition. Evaluation of within session patterns of responding indicates that the introduction of stimulus changes into the operant context reliably produced dishabituation of operant responding in humans., (© Society for the Experimental Analysis of Behavior.)

Unlabelled: Introduction The number of civilians killed in Iraq following the 2003 invasion has proven difficult to measure and contentious in recent years. The release of the Wikileaks War Logs (WL) has created the potential to conduct a sensitivity analysis of the commonly-cited Iraq Body Count's (IBC's) tally, which is based on press, government, and other public sources. Hypothesis The 66,000 deaths reported in the Wikileaks War Logs are mostly the same events as those previously reported in the press and elsewhere as tallied by iraqbodycount.org., Methods: A systematic random sample of 2500 violent fatal War Log incidents was selected and evaluated to determine whether these incidents were also found in IBC's press-based listing. Each selected event was ranked on a scale of 0 (no match present) to 3 (almost certainly matched) with regard to the likelihood it was listed in the IBC database., Results: Of the two thousand four hundred and nine War Log records, 488 (23.8%) were found to have likely matches in IBC records. Events that killed more people were far more likely to appear in both datasets, with 94.1% of events in which ≥20 people were killed being likely matches, as compared with 17.4% of singleton killings. Because of this skew towards the recording of large events in both datasets, it is estimated that 2035 (46.3%) of the 4394 deaths reported in the Wikileaks War Logs had been previously reported in IBC., Conclusions: Passive surveillance systems, widely seen as incomplete, may also be selective in the types of events detected in times of armed conflict. Bombings and other events during which many people are killed, and events in less violent areas, appear to be detected far more often, creating a skewed image of the mortality profile in Iraq. Members of the press and researchers should be hesitant to draw conclusions about the nature or extent of violence from passive surveillance systems of low or unknown sensitivity.

Efficient rejection prophylaxis and excellent short-term results in organ transplantation can not obscure the fact that long-term outcomes have not improved substantially over the last decade with rather constant graft attrition rates beyond the first year. There remains an unmet medical need for new immunosuppressive regimens to improve long-term graft and patient survival while carrying a low side effect burden. Several trials in renal transplant recipients are in the planning stages. In general there are two major strategies to improve outcomes: (a) the constant evolution of new immunosuppressive regimens with the currently approved immunosuppressants, and/or (b) the use of novel immunosuppressants. In this review, we give an overview of the most recent developments of novel immunosuppressive regimes. We show promising new immunosuppressive drugs and new immunosuppressive strategies serving as potential alternative's for calcineurin inhibitor-based regimens. Such regimens should provide similar efficacy and eventually better tolerability or a different side-effect profile with clinical benefits., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Urban children remain disproportionately at risk of having higher blood lead levels than their suburban counterparts. The Westside Cooperative Organization (WESCO), located in Marion County, Indianapolis, Indiana, has a history of children with high blood lead levels as well as high soil lead (Pb) values. This study aims at determining the spatial relationship between soil Pb sources and children's blood lead levels. Soils have been identified as a source of chronic Pb exposure to children, but the spatial scale of the source-recipient relationship is not well characterized. Neighborhood-wide analysis of soil Pb distribution along with a furnace filter technique for sampling interior Pb accumulation for selected homes (n = 7) in the WESCO community was performed. Blood lead levels for children aged 0-5 years during the period 1999-2008 were collected. The study population's mean blood lead levels were higher than national averages across all ages, race, and gender. Non-Hispanic blacks and those individuals in the Wishard advantage program had the highest proportion of elevated blood lead levels. The results show that while there is not a direct relationship between soil Pb and children's blood lead levels at a spatial scale of ~100 m, resuspension of locally sourced soil is occurring based on the interior Pb accumulation. County-wide, the largest predictor of elevated blood lead levels is the location within the urban core. Variation in soil Pb and blood lead levels on the community level is high and not predicted by housing stock age or income. Race is a strong predictor for blood lead levels in the WESCO community.