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Background Early in the pandemic, inadequate SARS-CoV-2 testing limited understanding of transmission. Chief among barriers to large-scale testing was unknown feasibility, particularly in non-urban areas. Our objective was to report methods of high-volume, comprehensive SARS-CoV-2 testing, offering one model to augment disease surveillance in a rural community. Methods A community-university partnership created an operational site used to test most residents of Bolinas, California regardless of symptoms in 4 days (April 20th – April 23rd, 2020). Prior to testing, key preparatory elements included community mobilization, pre-registration, volunteer recruitment, and data management. On day of testing, participants were directed to a testing lane after site entry. An administrator viewed the lane-specific queue and pre-prepared test kits, linked to participants’ records. Medical personnel performed sample collection, which included finger prick with blood collection to run laboratory-based antibody testing and respiratory specimen collection for polymerase chain reaction (PCR). Results Using this 4-lane model, 1,840 participants were tested in 4 days. A median of 57 participants (IQR 47–67) were tested hourly. The fewest participants were tested on day 1 (n = 338 participants), an intentionally lower volume day, increasing to n = 571 participants on day 4. The number of testing teams was also increased to two per lane to allow simultaneous testing of multiple participants on days 2–4. Consistent staffing on all days helped optimize proficiency, and strong community partnership was essential from planning through execution. Conclusions High-volume ascertainment of SARS-CoV-2 prevalence by PCR and antibody testing was feasible when conducted in a community-led, drive-through model in a non-urban area.

Background In Namibia, as in many malaria elimination settings, reactive case detection (RACD), or malaria testing and treatment around index cases, is a standard intervention. Reactive focal mass drug administration (rfMDA), or treatment without testing, and reactive focal vector control (RAVC) in the form of indoor residual spraying, are alternative or adjunctive interventions, but there are limited data regarding their community acceptability. Methods A parent trial aimed to compare the effectiveness of rfMDA versus RACD, RAVC versus no RAVC, and rfMDA + RAVC versus RACD only. To assess acceptability of these interventions, a mixed-methods study was conducted using key informant interviews (KIIs) and focus group discussions (FGDs) in three rounds (pre-trial and in years 1 and 2 of the trial), and an endline survey. Results In total, 17 KIIs, 49 FGDs were conducted with 449 people over three annual rounds of qualitative data collection. Pre-trial, community members more accurately predicted the level of community acceptability than key stakeholders. Throughout the trial, key participant motivators included: malaria risk perception, access to free community-based healthcare and IRS, and community education by respectful study teams. RACD or rfMDA were offered to 1372 and 8948 individuals in years 1 and 2, respectively, and refusal rates were low ( Conclusions Communities found both reactive focal interventions and their combination highly acceptable. Engaging communities and centering and incorporating their perspectives and experiences during design, implementation, and evaluation of this community-based intervention was critical for optimizing study engagement.

IntroductionTo reduce malaria transmission in very low-endemic settings, screening and treatment near index cases (reactive case detection (RACD)), is widely practiced, but the rapid diagnostic tests (RDTs) used miss low-density infections. Presumptive treatment near index cases (reactive focal mass drug administration (rfMDA)) may be safe and more effective.MethodsWe conducted a cluster-randomised controlled trial in Eswatini, a very low-endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisin-piperaquine (DP) or RACD involving RDTs and artemether lumefantrine (AL). Interventions were delivered by the local programme. An intention-to-treat analysis was used to compare cluster-level cumulative confirmed malaria incidence among clusters with cases. Secondary outcomes included safety and adherence.ResultsFrom Sept 2015–Aug 2017, 220 index cases from 47 clusters triggered 49 RACD events and 68 rfMDA events. RACD and rfMDA were delivered to 1696 and 1932 individuals, respectively. Index case and target population intervention coverages for both arms were 75.6%–81.4% and adherence to DP was 98.7%. For rfMDA versus RACD, cumulative incidences (per 1000 person-years) of all malaria were 2.11 (95% CI 1.73–2.59) and 1.97 (1.57–2.47), respectively; and of locally acquired malaria, they were 1.29 (95% CI 1.00–1.67) and 0.97 (0.71–1.34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio (aIRR) for rfMDA versus RACD was 0.93 (95% CI 0.54–1.60) for all malaria and 0.77 (95% CI 0.38–1.56) for locally acquired malaria. No serious adverse events occurred.ConclusionIn a very low-endemic, real-world setting, this trial is the first to evaluate rfMDA using DP. rfMDA was safe and resulted in lower cumulative incidence compared to RACD, but we were unable to confirm its effectiveness, potentially due to insufficient power. To assess impact of interventions in very low-endemic settings, multi-site, adaptive trials and use of complementary interventions may be needed.What is already known?Reactive case detection (RACD), or malaria testing and treatment in the vicinity of passively detected malaria cases, is a standard of care intervention used in low and very low transmission settings aiming for malaria elimination.Despite the use of RACD, progress toward malaria elimination has stalled in many countries and new strategies are needed.Reactive focal mass drug administration (rfMDA) is a transmission reducing strategy that has been shown to be effective in a low transmission setting, but there are no trial data from a very low transmission setting.What are the new findings?In a pragmatic, cluster-randomised controlled trial of rfMDA using dihydroartemisinin-piperaquine compared to RACD, we found that rfMDA was safe.rfMDA resulted in lower cumulative incidence, but we were unable to confirm its effectiveness compared to RACD, potentially due to insufficient power (we expected 63 total clusters would have incident cases, but observed 47).What do the new findings imply?When implemented in a real-world, very low transmission setting, rMDA was safe but evidence regarding its effectiveness to reduce transmission was weak.The challenge to show a statistically significant impact of a targeted community-based intervention in a very low transmission setting highlights the need for such trials to be multi-site, adaptive, and consider use of complementary interventions.

Background: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p Interpretation: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

INTRODUCTION PARAGRAPHMultiple large COVID-19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating that some infection susceptibility and severity risk is heritable.1-5 Most of these studies ascertained COVID-19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID-19 outcomes: four that align with previously studied COVID-19 definitions and four novel definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 13 previously identified COVID-19 genetic associations with all eight phenotypes and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. We then performed a discovery GWAS, which suggested some novel phenotypes may better capture protective associations and also identified a novel association in chr11/GALNT18 that reproduced in two fully independent populations.

IntroductionTo reduce malaria transmission in very low-endemic settings, screening and treatment near index cases (reactive case detection (RACD)), is widely practised, but the rapid diagnostic tests (RDTs) used miss low-density infections. Reactive focal mass drug administration (rfMDA) may be safe and more effective.MethodsWe conducted a pragmatic cluster randomised controlled trial in Eswatini, a very low-endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisin–piperaquine (DP) or RACD involving RDTs and artemether–lumefantrine. Interventions were delivered by the local programme. An intention-to-treat analysis was used to compare cluster-level cumulative confirmed malaria incidence among clusters with cases. Secondary outcomes included safety and adherence.ResultsFrom September 2015 to August 2017, 222 index cases from 47 clusters triggered 46 RACD events and 64 rfMDA events. RACD and rfMDA were delivered to 1455 and 1776 individuals, respectively. Index case coverage was 69.5% and 62.4% for RACD and rfMDA, respectively. Adherence to DP was 98.7%. No serious adverse events occurred. For rfMDA versus RACD, cumulative incidences (per 1000 person-years) of all malaria were 2.11 (95% CI 1.73 to 2.59) and 1.97 (95% CI 1.57 to 2.47), respectively; and of locally acquired malaria, they were 1.29 (95% CI 1.00 to 1.67) and 0.97 (95% CI 0.71 to 1.34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio for rfMDA versus RACD was 0.93 (95% CI 0.54 to 1.62) for all malaria and 0.84 (95% CI 0.42 to 1.66) for locally acquired malaria. Similar results were obtained in a per-protocol analysis that excluded clusters with ConclusionIn a very low-endemic, real-world setting, rfMDA using DP was safe, but did not lower incidence compared with RACD, potentially due to insufficient coverage and/or power. To assess impact of interventions in very low-endemic settings, improved coverage, complementary interventions and adaptive ring trial designs may be needed.Trial registration numberNCT02315690.

Aim To determine the rate and types of unreported maternal and neonatal complications in a rural community hospital in Malawi. Background The problem of maternal and neonatal morbidity and mortality may be underestimated, with underreporting of complications often noted. Reliable data is needed to make key decisions at the local, district, and national level. This study investigated whether there were unreported complications among women receiving intrapartum care at a rural community hospital in Malawi. Methods A retrospective cross-sectional study was conducted comparing maternity register records to client charts from January-March 2018. Descriptive data analysis using SPSS v20 was performed to calculate percentages and frequencies. Results 360 client cases were identified, of which 33 cases were excluded from analysis due to missing charts. Of the remaining 327 cases included in the final analysis, only 34% (n = 31) of maternal and 34% (n = 33) of neonatal complications were recorded in both the maternity register and the chart. When the additional complications found in the chart review were included, the rates of maternal and neonatal complications tripled from 9.5% (n = 31) and 10% (n = 33) to 28% (n = 90) and 30% (n = 98), respectively. Conclusions There was poor record keeping, underreporting of maternal and neonatal complications, and discrepancies between the data recorded in the monthly maternity register and client charts in the first quarter of 2018. The actual rate of complications suggests a need to verify data at the facility level to prevent release and reporting of inaccurate data. Measures are needed to mitigate the gaps in data reporting.

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, P=4.5x10-13) that down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.

BackgroundThe enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analyzing population-scale datasets in real time to monitor and better understand the evolving pandemic.MethodsThe AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors, and exposures for over 563,000 adult individuals in the U.S. in just under four months, including over 4,700 COVID-19 cases as measured by a self-reported positive test.ResultsWe replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for males even after adjusting for known exposures and age (adjusted odds ratio [aOR]=1.36, 95% confidence interval [CI] = (1.19, 1.55)). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualized COVID-19 susceptibility (area under the curve [AUC]=0.84) and severity outcomes including hospitalization and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex, and genetic ancestry groups within the study.ConclusionThe results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.THUMBNAILWhat is already known on this subjectThe COVID-19 pandemic has exacted a historic toll on human lives, healthcare systems and global economies, with over 83 million cases and over 1.8 million deaths worldwide as of January 2021.COVID-19 risk factors for susceptibility and severity have been extensively investigated by clinical and public health researchers.Several groups have developed risk models to predict COVID-19 illness outcomes based on known risk factors.What this study addsWe performed association analyses for COVID-19 susceptibility and severity in a large, at-home survey and replicated much of the previous clinical literature.Associations were further adjusted for known COVID-19 exposures, and we observed elevated positive test odds for males even after adjustment for these known exposures.We developed risk models and evaluated them across different age, sex, and genetic ancestry cohorts, and showed robust performance across all cohorts in a holdout dataset.Our results establish large-scale, self-reported surveys as a potential framework for investigating and monitoring rapidly evolving pandemics.

BackgroundWhile health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes. MethodsThis study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved.ResultsInitially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed.ConclusionsMobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient’s presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions.

Background New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children. Methods Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion. Results At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up. Conclusion The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.

Background Bovine leukemia virus (BLV) and human papillomavirus (HPV) were previously identified in human breast tissue and have been associated with breast cancer in independent studies. The objective of the current study was to test for the presence of BLV and HPV in the same breast tissue specimens to determine whether the viruses were associated with breast cancer either singly or together. Methods Archival formalin-fixed paraffin-embedded breast tissue sections from 216 women were received from The University of Texas MD Anderson Cancer Center along with patient diagnosis. In situ polymerase chain reaction and/or DNA hybridization methods were used to detect targeted DNA segments of BLV and HPV. Standard statistical methods were used to calculate age-adjusted odds ratios, attributable risk, and P values for the trend related to the association between presence of a virus and a diagnosis of breast disease. Results Women diagnosed with breast cancer were significantly more likely to have BLV DNA in their breast tissue compared with women with benign diagnoses and no history of breast cancer. Women with breast pathology classified as premalignant and no history of breast cancer also were found to have an elevated risk of harboring BLV DNA in their breast tissue. HPV status was not associated with malignancy, premalignant breast disease, or the presence of BLV in the breast tissues. Conclusions The data from the current study supported previous findings of a significant association between BLV DNA in breast tissue and a diagnosis of breast cancer, but did not demonstrate oncogenic strains of HPV associated with breast cancer or the presence of BLV DNA in breast tissue. The authors believe the findings of the current study contribute to overall knowledge regarding a possible causal role for viruses in human breast cancer. Cancer 2018;124:1342-9. © 2017 American Cancer Society.

Background Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. Methods A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. Results The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. Conclusion Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-2021-7) contains supplementary material, which is available to authorized users.

Background Preterm birth in the United States is associated with maternal clinical factors such as diabetes, hypertension and social factors including race, ethnicity, and socioeconomic status. In California, 8.7% of all live births are preterm, with African American and Black families experiencing the greatest burden. The impact of paternal factors on birth outcomes has been studied, but little is known about the experience of men of color (MOC). The purpose of this study was to explore the experiences of MOC who are partners to women at medical and social risk for preterm birth. Methods This study used a qualitative research design and focus group methods. The research was embedded within an existing study exploring experiences of women of color at risk for preterm birth conducted by the California Preterm Birth Initiative. Results Twelve MOC participated in the study and among them had 9 preterm children. Four themes emerged from thematic analysis of men’s experiences: (1) “Being the Rock”: Providing comfort and security; (2) “It’s a blessing all the way around”: Keeping faith during uncertainty; (3) “Tell me EVERYTHING”: Unmet needs during pregnancy and delivery; (4) “Like a guinea pig”: Frustration with the healthcare system. Participants identified many barriers to having a healthy pregnancy and birth including inadequate support for decision making, differential treatment, and discrimination. Conclusions This study shows novel and shared narratives regarding MOC experiences during pregnancy, birth, and postpartum periods. Healthcare providers have an essential role to acknowledge MOC, their experience of discrimination and mistrust, and to assess needs for support that can improve birth outcomes. As MOC and their families are at especially high social and medical risk for preterm birth, their voice and experience should be central in all future research on this topic.

International audience; For the 12 GeV upgrade of Jefferson Laboratory, a Silicon Vertex Tracker (SVT) has been designed for the CLAS12 spectrometer using single-sided microstrip sensors fabricated by Hamamatsu Photonics. The sensors have a graded angle design to minimize dead areas and a readout pitch of 156μm , with intermediate strips. Each double-sided SVT module hosts three daisy-chained sensors on each side with a full strip length of 33 cm. There are 512 channels per module, read out by four Fermilab Silicon Strip Readout (FSSR2) chips, featuring data-driven architecture, mounted on a rigid–flex hybrid board. The modules are assembled in a barrel configuration using a unique cantilevered geometry to minimize the amount of material in the tracking volume. This paper is focused on the design, qualification of the performance, and experience in operating and commissioning the tracker during the first year of the data taking.

International audience; We describe offline event reconstruction for the CEBAF Large Acceptance Spectrometer at 12 GeV (CLAS12), including an overview of the offline reconstruction framework and software tools, a description of the algorithms developed for the individual detector subsystems, and the overall approach for charged and neutral particle identification. We also present the scheme for data processing and the code management procedures.

Background: Screening and treatment near malaria index cases (reactive case detection (RACD)), is widely practiced, but the rapid diagnostic tests (RDTs) used miss low density infections. Presumptive treatment near index cases (reactive focal mass drug administration (rfMDA)) may be safe and more effective but has not been evaluated in very low-endemic settings. Methods: A cluster-randomised controlled trial was conducted in Eswatini, a very low -endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisinin-piperaquine (DP) or RACD involving RDTs and artemether lumefantrine (AL), administered within 200 or 500 m of index cases, respectively. Interventions were delivered by the local programme, and evaluated using an intention-to-treat analysis. Findings: From Sept 2015–Aug 2017, 220 index cases from 47 clusters triggered 49 RACD events and 68 rfMDA events. RACD and rfMDA were delivered to 1 696 and 1 932 individuals, respectively. For rfMDA versus RACD, cumulative incidences (per 1 000 person-years) of all malaria were 2·11 (95% CI 1·73–2·59) and 1·97 (1·57–2·47), respectively; and of locally acquired malaria, they were 1·29 (95% CI 1·00–1·67) and 0·97 (0·71–1·34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio (aIRR) for rfMDA versus RACD was 0·93 (95% CI 0·54–1·60) for all malaria and 0·77 (95% CI 0·38–1·56) for locally acquired malaria. No serious adverse events occurred. Interpretation: In a very low-endemic, real-world setting, rfMDA was safe. There was limited statistical power to estimate its effectiveness compared to RACD. Trial Registration: This trial is registered with the ClinicalTrials.gov (NCT02315690). Funding Statement: This study was supported by the Bill & Melinda Gates Foundation (A122394) and the Horchow Family Fund (5300375400). Declaration of Interests: The authors have no competing interests to report. Ethics Approval Statement: Ethics approval was obtained from Eswatini Ministry of Health (MOH) (MH/599C) and University of California San Francisco (14-15226). Written informed consent was obtained from individual participants. For children less than 18 years, written informed consent from a parent or guardian was required, as was written assent for children 12–17 years.

BackgroundThe misdiagnosis of non-malarial fever in sub-Saharan Africa has contributed to the significant burden of pediatric pneumonia and the inappropriate use of antibiotics in this region. This study aims to assess the impact of 1) portable pulse oximeters and 2) Integrated Management of Childhood Illness (IMCI) continued education training on the diagnosis and treatment of non-malarial fever amongst pediatric patients being treated by the Global AIDS Interfaith Alliance (GAIA) in rural Malawi.MethodsThis study involved a logbook review to compare treatment patterns between five GAIA mobile clinics in Mulanje, Malawi during April-June 2019. An intervention study design was employed with four study groups: 1) 2016 control, 2) 2019 control, 3) IMCI-only, and 4) IMCI and pulse oximeter. A total of 3,504 patient logbook records were included based on these inclusion criteria: age under five years, febrile, malaria-negative, and treated during the dry season. A qualitative questionnaire was distributed to the participating GAIA providers. Fisher’s Exact Testing and odds ratios were calculated to compare the prescriptive practices between each study group and reported with 95% confidence intervals.ResultsThe pre- and post-exam scores for the providers who participated in the IMCI training showed an increase in content knowledge and understanding (p0.001). However, provider responses to the qualitative questionnaires indicated alternative benefits of the training including improved illness classification and increased provider confidence.ConclusionClinics that implemented both the IMCI course and pulse oximeters exhibited a significant decrease in antibiotic prescription rates, thus highlighting the potential of this tool in combatting antibiotic overconsumption in low-resource settings. Enhanced detection of hypoxia in pediatric patients was regarded by clinicians as helpful for identifying pneumonia cases. GAIA staff appreciated the IMCI continued education training, however it did not appear to significantly impact antibiotic prescription rates and/or pneumonia diagnosis.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

Background In light of increasing complexity of identifying and treating malaria cases in low transmission settings, operational solutions are needed to increase effective delivery of interventions. Community engagement (CE) is at the forefront of this conversation given the shift toward creating local and site-specific solutions. Malaria programmes often confuse CE with providing information to the community or implementing community-based interventions. This study seeks to expand on CE approaches for malaria by looking to a variety of health and development programmes for lessons that can be applied to malaria elimination. Methods Qualitative data was collected from key informant interviews and community-based focus group discussions. Manual analysis was conducted with a focus on key principles, programme successes and challenges, the operational framework, and any applicable results. Results Ten programmes were included in the analysis: Ebola, HIV/Hepatitis C, Guinea worm, malaria, nutrition, and water, sanitation and hygiene. Seven focus group discussions (FGDs) with 69 participants, 49 key informant (KI) interviews with programme staff, and 7 KI interviews with thought leaders were conducted between October–April 2018. Participants discussed the critical role that village leaders and community health workers play in CE. Many programmes stated understanding community priorities is key for CE and that CE should be proactive and iterative. A major theme was prioritizing bi-directional interpersonal communication led by local community health workers. Programmes reported that measuring CE is difficult, particularly since CE is ongoing and fluid. Conclusions Results overwhelmingly suggest that CE must be an iterative process that relies on early involvement, frequent feedback and active community participation to be successful. Empowering districts and communities in planning and executing community-based interventions is necessary. Communities affected by the disease will ultimately achieve malaria elimination. For this to happen, the community itself must define, believe in, and commit to strategies to interrupt transmission. Electronic supplementary material The online version of this article (10.1186/s12936-019-2878-8) contains supplementary material, which is available to authorized users.

Background Reactive focal mass drug administration (rfMDA), or presumptive treatment without malaria testing of household members and neighbours of a passively identified malaria case, is currently being explored as a possible malaria elimination strategy in low transmission settings. One of the primary factors determining the effectiveness of rfMDA on reducing or interrupting transmission is achieving high coverage of the target population with drug administration. This study aims to explore the acceptability of rfMDA and identify facilitators and barriers to its potential implementation, as well as the community’s general knowledge, attitudes and beliefs with regard to malaria elimination. Methods A qualitative study was performed using focus group discussions (FGDs) among villagers that received rfMDA through the National Malaria Control Programme in the low transmission setting of Eswatini as part of a 2-year clinical trial. FGDs were audio-recorded, transcribed and translated into English. All transcripts were managed in Dedoose and underwent qualitative content analysis. Results The majority of participants perceived their community to be at high risk of malaria. Witnessing others in their community suffer from malaria, proximity to Mozambique, various ecological factors, and the presence of mosquitoes contributed to this perception. The greatest motivator of participation in rfMDA was witnessing someone else suffer from malaria, since most participants had not personally experienced malaria themselves. Participants valued the education on rfMDA and on malaria in general, particularly when communicated by nurses and other health workers from the Ministry of Health. Participants were overwhelmingly motivated to participate in rfMDA in order to obtain protection from malaria. Most participants did not understand the concept of sub-clinical infection and, therefore, did not perceive the anti-malarial medication given in rfMDA to be a treatment medication. Conclusions Perceived risk for malaria was a major driver of acceptability; therefore, future intervention campaigns could aim to better quantify risk to inform interventions and encourage uptake. There were misunderstandings about the asymptomatic reservoir of parasites in humans. Given that this phenomenon is the rationale for rfMDA, this misunderstanding could threaten the uptake of the intervention if it persists in the community. Using local authorities to deliver messaging, additional education on this concept with re-inforcement that risk of malaria is ongoing, even in the absence of frequent cases, may help to maximize and maintain acceptability.

Introduction With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making. Methods A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5oC or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication. Results In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions. Conclusion Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

© 2017 by The American Society of Tropical Medicine and Hygiene. Infectious disease continues to adversely affect populations in low- and middle-income countries. Investments in solutions often focus on technology, yet health-care workers remain in short supply. Nurses are the largest cadre of health-care workers and are largely responsible for patient care around the world. In fact, it is estimated that nurses care for nine out of every 10 patients seen. Importantly, sound nursing science contributes to solutions that directly impact patient care, especially those that pertain to infectious disease. Here we share several examples of nursing science that are improving care delivery in three global health areas: Human immunodeficiency virus testing and prevention strategies in Malawi, family planning in Kenya, and response to Ebola virus disease.

Recent studies have uncovered a neural response that appears to track the envelope of speech, and have shown that this tracking process is mediated by attention. It has been argued that this tracking reflects a process of phase-locking to the fluctuations of stimulus energy, ensuring that this energy arrives during periods of high neuronal excitability. Because all acoustic stimuli are decomposed into spectral channels at the cochlea, and this spectral decomposition is maintained along the ascending auditory pathway and into auditory cortex, we hypothesized that the overall stimulus envelope is not as relevant to cortical processing as the individual frequency channels; attention may be mediating envelope tracking differentially across these spectral channels. To test this we reanalyzed data reported by Horton et al. (2013), where high-density EEG was recorded while adults attended to one of two competing naturalistic speech streams. In order to simulate cochlear filtering, the stimuli were passed through a gammatone filterbank, and temporal envelopes were extracted at each filter output. Following Horton et al. (2013), the attended and unattended envelopes were cross-correlated with the EEG, and local maxima were extracted at three different latency ranges corresponding to distinct peaks in the cross-correlation function (N1, P2, and N2). We found that the ratio between the attended and unattended cross-correlation functions varied across frequency channels in the N1 latency range, consistent with the hypothesis that attention differentially modulates envelope-tracking activity across spectral channels.

International audience; The CLAS12 Data Acquisition System was designed and built as part of the CLAS12 detector project in Hall B at Jefferson Laboratory. This article contains a full description of the system, including requirements, design, hardware, and software descriptions, as well as the achieved performance. The associated computing, network, and slow controls systems are also described.

This paper describes the Hall B beamline and its performance during the first year of data-taking operation using the CLAS12 detector. We review the beamline instrumentation used to measure and monitor the beam. This instrumentation led to excellent beam quality for energies ranging from 2.2 to 10.6 GeV at the design luminosity of 1 0 35 cm−2s−1. The instrumentation includes a Moller polarimeter, which can typically measure the beam polarization to an absolute precision of ∼ 2.5%.

Changing a sport system requires the appointment of new leaders or a grass roots cultural revolution. ‘I got caught in a system designed by and for men, which destroys the bodies of young girls,’ said Mary Cain as she cast light on her toxic coach/athlete relationship and exposed unhealthy coaching and nutrition practices. Her candour has inspired a social media movement calling for changes to women’s sport.1 In the following days, major news publications followed up with similar reports of athletic women being body shamed.2–4 It is time for a drastic paradigm change in women’s sport, coupled with education at all levels to improve the long-term health and athletic achievement of female athletes. The shift needs to include: 1. Raising awareness of the negative effects of chronic low energy availability (LEA) (calorie restriction) so athletes can make wise choices for their own long-term health. 2. Updating and developing best-practice protocols and safe standards for monitoring body composition/weight. 3. Eliminating toxic training environments featuring abusive body shaming. Overexercising or underfueling, occurring consciously or subconsciously, can cause Relative …

The importance of academic publications is often evaluated by the number of and impact of its subsequent citing works. These citing works build upon the referenced material, representing both further intellectual insights and additional derived uses. As such, reading peer-reviewed articles which cite one’s work can serve as a way for authors to understand how their research is being adopted and extended by the greater scientific community, further develop the broader impacts of their research, and even find new collaborators. Unfortunately, in today’s rapidly growing and shifting scientific landscape, it is unlikely that a researcher has enough time to read through all articles citing their works, especially in the case of highly-cited broad-impact studies. To address this challenge, we developed the Science Citation Knowledge Extractor (SCKE), a web tool to provide biological and biomedical researchers with an overview of how their work is being utilized by the broader scientific community. SCKE is a web-based tool which utilizes natural language processing and machine learning to retrieve key information from scientific publications citing a given work, analyze the citing material, and and present users with interactive data visualizations which illustrate how their works are contributing to greater scientific pursuits. Results are generally grouped into two categories, aimed at 1) understanding the broad scientific areas which one’s work is impacting and 2) assessing the breadth and impact of one’s work within these areas. As a web application, SCKE is easy to use, with a single input of PubMed ID(s) to analyze. SCKE is available for immediate use by the scientific community as a hosted web application at https://geco.iplantcollaborative.org/scke/. SCKE can also be self-hosted by taking advantage of a fully-integrated VM Image (https://tinyurl.com/y7ggpvaa), Docker container (https://tinyurl.com/y95u9dhw), or open-source code (GPL license) available on GitHub (https://tinyurl.com/yaesue5e).

Objective To use cortical auditory evoked potentials (CAEPs) to understand neural encoding in background noise and the conditions under which noise enhances CAEP responses. Methods CAEPs from 16 normal-hearing listeners were recorded using the speech syllable/ba/presented in quiet and speech-shaped noise at signal-to-noise ratios of 10 and 30 dB. The syllable was presented binaurally and monaurally at two presentation rates. Results The amplitudes of N1 and N2 peaks were often significantly enhanced in the presence of low-level background noise relative to quiet conditions, while P1 and P2 amplitudes were consistently reduced in noise. P1 and P2 amplitudes were significantly larger during binaural compared to monaural presentations, while N1 and N2 peaks were similar between binaural and monaural conditions. Conclusions Methodological choices impact CAEP peaks in very different ways. Negative peaks can be enhanced by background noise in certain conditions, while positive peaks are generally enhanced by binaural presentations. Significance Methodological choices significantly impact CAEPs acquired in quiet and in noise. If CAEPs are to be used as a tool to explore signal encoding in noise, scientists must be cognizant of how differences in acquisition and processing protocols selectively shape CAEP responses.

Summary Following polyploidy events, genomes undergo massive reduction in gene content through a process known as fractionation. Importantly, the fractionation process is not always random, and a bias as to which homeologous chromosome retains or loses more genes can be observed in some species. The process of characterizing whole genome fractionation requires identifying syntenic regions across genomes followed by post-processing of those syntenic datasets to identify and plot gene retention patterns. We have developed a tool, FractBias, to calculate and visualize gene retention and fractionation patterns across whole genomes. Through integration with SynMap and its parent platform CoGe, assembled genomes are pre-loaded and available for analysis, as well as letting researchers integrate their own data with security options to keep them private or make them publicly available. Availability and Implementation FractBias is freely available as a web application at https://genomevolution.org/CoGe/SynMap.pl. The software is open source (MIT license) and executable with Python 2.7 or iPython notebook, and available on GitHub (https://goo.gl/PaAtqy). Documentation for FractBias is available on CoGepedia (https://goo.gl/ou9dt6) Supplementary information Supplementary data are available at Bioinformatics online.

Judgment and Sensibility is the second volume of the collected essays of E. Digby Baltzell, one of the keenest observers and analysts of America's upper classes since Thorstein Veblen. Spanning four decades of writing, these essays cover a wide range of topics, including contemporary politics, democratic elitism, Puritanism, Judaism, higher education, urbanization, and the U.S. Supreme Court, among others.

Summary The EPIC-CoGe browser is a web-based genome visualization utility that integrates the GMOD JBrowse genome browser with the extensive CoGe genome database (currently containing over 30 000 genomes). In addition, the EPIC-CoGe browser boasts many additional features over basic JBrowse, including enhanced search capability and on-the-fly analyses for comparisons and analyses between all types of functional and diversity genomics data. There is no installation required and data (genome, annotation, functional genomic and diversity data) can be loaded by following a simple point and click wizard, or using a REST API, making the browser widely accessible and easy to use by researchers of all computational skill levels. In addition, EPIC-CoGe and data tracks are easily embedded in other websites and JBrowse instances. Availability and implementation EPIC-CoGe Browser is freely available for use online through CoGe (https://genomevolution.org). Source code (MIT open source) is available: https://github.com/LyonsLab/coge. Supplementary information Supplementary data are available at Bioinformatics online.

Objective. To characterize children with non–malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non–malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion. Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.

This workflow allows novice researchers to leverage advanced computational resources such as cloud computing to carry out pairwise comparative transcriptomics. It also serves as a primer for biologists to develop data scientist computational skills, e.g. executing bash commands, visualization and management of large data sets. All command line code and further explanations of each command or step can be found on the wiki (https://wiki.cyverse.org/wiki/x/dgGtAQ). The Discovery Environment and Atmosphere platforms are connected together through the CyVerse Data Store. As such, once the initial raw sequencing data has been uploaded there is no more need to transfer large data files over an Internet connection, minimizing the amount of time needed to conduct analyses. This protocol is designed to analyze only two experimental treatments or conditions. Differential gene expression analysis is conducted through pairwise comparisons, and will not be suitable to test multiple factors. This workflow is also designed to be manual rather than automated. Each step must be executed and investigated by the user, yielding a better understanding of data and analytical outputs, and therefore better results for the user. Once complete, this protocol will yield de novo assembled transcriptome(s) for underserved (non-model) organisms without the need to map to previously assembled reference genomes (which are usually not available in underserved organism). These de novo transcriptomes are further used in pairwise differential gene expression analysis to investigate genes differing between two experimental conditions. Differentially expressed genes are then functionally annotated to understand the genetic response organisms have to experimental conditions. In total, the data derived from this protocol is used to test hypotheses about biological responses of underserved organisms.

This study explored how members of a Division I varsity women’s soccer team experienced a 6-week, 12 session mindfulness meditation training for sport (MMTS) program. The coaching staff and entire team participated in the MMTS program. Seven of the team members volunteered to be interviewed after their participation in the MMTS program. Thematic analysis was implemented. Most participants reported difficulty understanding the process of meditation at the start of the MMTS program. Post-MMTS, they reported an enhanced ability to accept and experience a different relationship with their emotions, both on and off the field. They also noted the importance of creating a phrase of care for self and team for cohesion purposes. Enhanced mindfulness, awareness, and acceptance of emotional experiences were attributed directly to the mindfulness training. Participants provided specific recommendations for future sport-focused mindfulness meditation programs.

The global age standardized prevalence of type 2 diabetes (T2DM) has doubled (4.7% to 8.5%) over the last three decades and is increasing more rapidly in low and middle-income countries (LMICs). The global economic burden of diabetes affects individuals and health care systems and is estimated to cost $825 billion USD a year. Within Mexico, T2DM is the second leading cause of mortality and the leading cause of morbidity using disability associated life years (DALYs). A retrospective chart review and cost analysis, analyzing those at risk of diabetes, was conducted at a rural community health clinic in Jalisco, Mexico. The goal was to project the cost of providing an appropriate scope of care and plan prevention-based population health programs. The results demonstrated that out of 264 charts reviewed, 218 (83%) had one or more diabetic risk factor. The estimated per patient per visit cost is $127.22 MP (Mexican Peso, 2018) and as the number of diabetes risk factors increases for an individual patient, the mean cost of their care to the system increases (p < .001). Those with at least one risk factor comprise the majority in both males and females with a median age of 36 and median BMI of 28, and this group also has the highest percentage of borderline hypertension (46%). This data demonstrates an opportunity to intervene in a group of young adults (ages 27-46) with a cluster of high-risk borderline risk factors and preventing them from developing obesity, hypertension and diabetes later in life.

Objective: The purpose of this study was to determine the effects of SNR and signal level on the offset response of the cortical auditory evoked potential (CAEP). Successful listening often depends on how well the auditory system can extract target signals from competing background noise. Both signal onsets and offsets are encoded neurally and contribute to successful listening in noise. Neural onset responses to signals in noise demonstrate a strong sensitivity to signal-to-noise ratio (SNR) rather than signal level; however, the sensitivity of neural offset responses to these cues is not known. Methods: We analyzed the offset response from two previously published datasets for which only the onset response was reported. For both datasets, CAEPs were recorded from young normal-hearing adults in response to a 1000-Hz tone. For the first dataset, tones were presented at seven different signal levels without background noise, while the second dataset varied both signal level and SNR. Results: Offset responses demonstrated sensitivity to absolute signal level in quiet, SNR, and to absolute signal level in noise. Conclusions: Offset sensitivity to signal level when presented in noise contrasts with previously published onset results. Significance: This sensitivity suggests a potential clinical measure of cortical encoding of signal level in noise.

It has been suggested that cortical entrainment plays an important role in speech perception by helping to parse the acoustic stimulus into discrete linguistic units. However, the question of whether the entrainment response to speech depends on the intelligibility of the stimulus remains open. Studies addressing this question of intelligibility have, for the most part, significantly distorted the acoustic properties of the stimulus to degrade the intelligibility of the speech stimulus, making it difficult to compare across “intelligible” and “unintelligible” conditions. To avoid these acoustic confounds, we used priming to manipulate the intelligibility of vocoded speech. We used EEG to measure the entrainment response to vocoded target sentences that are preceded by natural speech (nonvocoded) prime sentences that are either valid (match the target) or invalid (do not match the target). For unintelligible speech, valid primes have the effect of restoring intelligibility. We compared the effect of priming on the entrainment response for both 3-channel (unintelligible) and 16-channel (intelligible) speech. We observed a main effect of priming, suggesting that the entrainment response depends on prior knowledge, but not a main effect of vocoding (16 channels vs. 3 channels). Furthermore, we found no difference in the effect of priming on the entrainment response to 3-channel and 16-channel vocoded speech, suggesting that for vocoded speech, entrainment response does not depend on intelligibility. NEW & NOTEWORTHY Neural oscillations have been implicated in the parsing of speech into discrete, hierarchically organized units. Our data suggest that these oscillations track the acoustic envelope rather than more abstract linguistic properties of the speech stimulus. Our data also suggest that prior experience with the stimulus allows these oscillations to better track the stimulus envelope.

It is easy to control yourself when you are feeling confident. When you are feeling good and want to be there, self-regulation is of no concern. Self-regulation is about being able to make choices about what you think, what you do, and where you place your attention, intentionally. When you have no constraints, no distractions, and a clear desire to perform, it predictably will take you little effort to get yourself locked-in and focused on performance. However, when athletes feel off, physically or emotionally, such as getting distracted by comparisons or competitors – comparing themselves to others and doubting if they are as strong, or fit, or tall, or steady or intense as they ideally should be – effortful self-regulation is needed. It can be easy for athletes to subsequently believe their thoughts (e.g., I can’t win!) and conclude that their physical signs (e.g., I just don’t feel right today.) are reliable information indicating that they will not be successful in their upcoming performance.

Ultimately MMTS 2.0 is designed to help you upgrade your performance (i.e., practice and competition) through helping you make better use of your attention and concentration when playing your sport. We hope to empower and inspire you to: 1. Give less power to distractions, upset (i.e., not allowing natural fear or dread get in the way of you focusing your attention on performing as well as you can, each moment). 2. Have less (unhelpful) reactivity to such upset (i.e., though the practices we offer in no way promise to stop such difficult emotions. Instead, you will be empowered to be less of a victim to them because you will learn to tolerate them and have the freedom to focus your attention where you want to place it!). 3. Lock-in your attention while adapting and adjust to what is occurring around you (i.e., you will be able to pay attention to your sport instead of to the uninvited thoughts and feelings surging through your mind and body).

Objectives\ud To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia. \ud Design\ud Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).\ud Setting\ud Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.\ud Participants\ud 522 480 children and adults with acute febrile illness.\ud Interventions\ud Rapid diagnostic tests for malaria.\ud Main outcome measures\ud Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.\ud Results\ud Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined. [Abstract copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.]

There are many ways to strengthen self-regulation, meaning speaking and acting in the way that you value, regardless of the push and pull of your emotions. It sounds easy to choose to focus your attention, where you choose to, until you get challenged by your emotions from distress, boredom to lack of fun. For example, the intense urge to lie down and take a nap sweeps through your body yet it is time to lace up and get to practice, what do you do? A teammate is lazy for a few days of practice leading up to a big competition and gets to start in the game over you, how do you react? You hear about a big party but have loads of work to do. What do you choose? Staying steady, being able to self-regulate, may be the most important overarching mental skill that you can develop to achieve your very best in sport. And in many ways, MMTS 2.0 and this book, are offering you myriad ways to do just this, strengthen your ability to choose to engage, concentrate, and stay engaged with the moment regardless of how you feel. And doing so based on your values. Sometimes it is important to take the nap or go to the party. We are empowering you to live your values.

Astronomical data sets are growing ever larger, and the area of high contrast imaging of exoplanets is no exception. With the advent of fast, low-noise detectors operating at 10 to 1000 Hz, huge numbers of images can be taken during a single hours-long observation. High frame rates offer several advantages, such as improved registration, frame selection, and improved speckle calibration. However, advanced image processing algorithms are computationally challenging to apply. Here we describe a parallelized, cloud-based data reduction system developed for the Magellan Adaptive Optics VisAO camera, which is capable of rapidly exploring tens of thousands of parameter sets affecting the Karhunen-Loeve image processing (KLIP) algorithm to produce high-quality direct images of exoplanets. We demonstrate these capabilities with a visible wavelength high contrast data set of a hydrogen-accreting brown dwarf companion.

Summary Current synteny visualization tools either focus on small regions of sequence and do not illustrate genome-wide trends, or are complicated to use and create visualizations that are difficult to interpret. To address this challenge, The Comparative Genomics Platform (CoGe) has developed two web-based tools to visualize synteny across whole genomes. SynMap2 and SynMap3D allow researchers to explore whole genome synteny patterns (across two or three genomes, respectively) in responsive, web-based visualization and virtual reality environments. Both tools have access to the extensive CoGe genome database (containing over 30 000 genomes) as well as the option for users to upload their own data. By leveraging modern web technologies there is no installation required, making the tools widely accessible and easy to use. Availability and Implementation Both tools are open source (MIT license) and freely available for use online through CoGe (https://genomevolution.org). SynMap2 and SynMap3D can be accessed at http://genomevolution.org/coge/SynMap.pl and http://genomevolution.org/coge/SynMap3D.pl, respectively. Source code is available: https://github.com/LyonsLab/coge. Supplementary information Supplementary data are available at Bioinformatics online.

BACKGROUND: Human papillomavirus (HPV) has been proposed as an etiologic agent of breast cancer based on numerous reports of high-risk (oncogenic) HPV types in malignant breast tissues. However, most of those studies used standard and nested solution polymerase chain reaction (PCR) techniques, both of which are disadvantaged by vulnerability to laboratory contamination from positive control DNA and the inability to localize the signal to a specific cell type. To overcome these drawbacks, the authors of this report explored the use of in situ molecular methods of viral detection to reassess the frequency of HPV in malignant breast tissue. METHODS: In situ hybridization (ISH) was used with probes that were specific for the capsid region of 12 oncogenic HPV types, and in situ PCR (IS-PCR) was used with primers that were specific for the capsid region of HPV-16, which is the most common oncogenic HPV type. These methods were resistant to molecular contamination and allowed identification of the positive cell type. The specimens examined were malignant tissues from patients with 70 breast cancer patients at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. RESULTS: HPV was observed in 4 of 70 specimens (5.7%) using ISH and in 2 of 70 specimens (2.9%) of specimens using IS-PCR. Concordance between the 2 methods was high for negative specimens; both methods yielded negative results in 66 of 70 specimens (94.3%). However, there was no concordance for the few positive specimens, probably because of differences in sensitivity and the targeted HPV types. CONCLUSIONS: Oncogenic (high-risk) HPV types were present in malignant breast epithelium very infrequently and, thus, may be causative agents of only a relatively small proportion of all breast cancers. Cancer 2012;. © 2011 American Cancer Society.

Herrington CS, Prekker ME, Arrington AK, Susanto D, Baltzell JW, Studenski LL, Radosevich DM, Kelly RF, Shumway SJ, Hertz MI, Bittner HB, Dahlberg PS. A randomized, placebo-controlled trial of aprotinin to reduce primary graft dysfunction following lung transplantation. Clin Transplant 2011: 25: 90–96. © 2010 John Wiley & Sons A/S. Abstract: Purpose: Severe primary graft dysfunction (PGD) is the major early problem following lung transplantation. Aprotinin, a serine protease inhibitor, has many anti-inflammatory properties that might reduce or prevent lung injury. Our hypothesis was that the incidence of PGD could be reduced by a combination of donor lung perfusion and systemic administration of aprotinin to recipients. Methods and Materials: The study was randomized and placebo controlled. Donor lungs were perfused during procurement with 4 L Perfadex containing aprotinin (280 mg load + 70 mg/hL) or placebo. Aprotinin or placebo was also administered peri-operatively to the recipients. The study was powered to detect a 10% improvement in the primary endpoint of developing ISHLT grade III PGD anytime within 48 hr following the transplant procedure. Results: There were 48 patients randomized. Diagnosis and the use of bypass were different between groups. The study was stopped prematurely at the planned interim analysis point because of published concerns about renal toxicity of aprotinin. There was no difference in the occurrence of the primary endpoint between groups of patients. The median change from the baseline creatinine level at 24, 48, 72 hr; 7 and 30 d following the transplant was not associated with the administration of aprotinin. Conclusions: There was no statistically significant difference in the incidence of the primary endpoint between groups in the study. Excess renal failure related to aprotinin administration in a patient population at high risk for the event was not observed.