Mapping the spatial distribution of the Japanese encephalitis vector, Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) within areas of Japanese encephalitis risk

Background Japanese encephalitis (JE) is one of the most significant aetiological agents of viral encephalitis in Asia. This medically important arbovirus is primarily spread from vertebrate hosts to humans by the mosquito vector Culex tritaeniorhynchus. Knowledge of the contemporary distribution of this vector species is lacking, and efforts to define areas of disease risk greatly depend on a thorough understanding of the variation in this mosquito’s geographical distribution. Results We assembled a contemporary database of Cx. tritaeniorhynchus presence records within Japanese encephalitis risk areas from formal literature and other relevant resources, resulting in 1,045 geo-referenced, spatially and temporally unique presence records spanning from 1928 to 2014 (71.9% of records obtained between 2001 and 2014). These presence data were combined with a background dataset capturing sample bias in our presence dataset, along with environmental and socio-economic covariates, to inform a boosted regression tree model predicting environmental suitability for Cx. tritaeniorhynchus at each 5 × 5 km gridded cell within areas of JE risk. The resulting fine-scale map highlights areas of high environmental suitability for this species across India, Nepal and China that coincide with areas of high JE incidence, emphasising the role of this vector in disease transmission and the utility of the map generated. Conclusions Our map contributes towards efforts determining the spatial heterogeneity in Cx. tritaeniorhynchus distribution within the limits of JE transmission. Specifically, this map can be used to inform vector control programs and can be used to identify key areas where the prevention of Cx. tritaeniorhynchus establishment should be a priority

Portfolio Vol. I N 3

Sweitzer, Harry J. Portfolio Goes to Press . Prose. 1. Browne, Phil. William Howard Doane Library . Picture. 2. Overhuls, James. Out of Himself . Prose. 3. MacNeill, Annie Marie. To President and Mrs. Shaw . Poem. 6. Baker, George. Saint in a Silo . Prose 7. Beckham, Adela. In Moods . Poem. 8. Vincent, Charles. Incident of August 7, 1930. Prose. 9. Flory, Doris. Opinions . Poem. 10. Flory, Doris. Thoughts in Spring . Poem. 10. Flory, Doris. Breakfast Scene . Poem. 10. Shaw, Robert B. A Date for the Dances . Prose. 11. Cronberger, Barbara. And the Years Go On . Prose. 13. Hanna, Stanley. Reola, Reola . Poem. 14. Hanna, Stanley. The Dance of the Kobolds . Poem. 14. Nadel, Norman. I died Last Night . Prose. 15. Bethune, Don S. Adolescence . Poem 16. Vodev, Eugene. The Black Day of Bulgaria . Prose. 17. Dick, Pewilla. To a White Violet . Poem. 18. Dick, Pewilla. As With Your Shadow . Poem. 18. Dwelly, Thorndike. Of Mice and Men . Prose. 19. Clements, Helen. Our Town . Prose. 19. Schlle, Alice. Marion is an Old Costume . Picture. 20. Chadeayne, Robert. Factory . Picture. 20. Nadel, Norman. Dmitri Shostakovitch . Prose. 21. Stewart, John. Duke Ellington\u27s Records . Prose. 21. Beck, Virginia. The Dance as an Art . Prose. 22. Dick, Pewilla. Death . Poem. 23. Flory, Doris. On Reforms . Poem. 24. Beckham, Adela. The Lie . Poem. 24. Bethune, Don. Futility . Poem. 24

Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis.

BACKGROUND: Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the disease's contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. METHODS: We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. FINDINGS: Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016 was estimated to be substantially less than the recommended threshold to prevent outbreaks. Overall, we estimated that vaccination coverage levels achieved by 2016 avert between 94 336 and 118 500 cases of yellow fever annually within risk zones, on the basis of conservative and optimistic vaccination scenarios. The areas outside at-risk regions with predicted high receptivity to yellow fever transmission (eg, parts of Malaysia, Indonesia, and Thailand) were less extensive than the distribution of the main urban vector, A aegypti, with low receptivity to yellow fever transmission in southern China, where A aegypti is known to occur. INTERPRETATION: Our results provide the evidence base for targeting vaccination campaigns within risk zones, as well as emphasising their high effectiveness. Our study highlights areas where public health authorities should be most vigilant for potential spread or importation events. FUNDING: Bill & Melinda Gates Foundation

Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

BACKGROUND: Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. METHODS: For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. FINDINGS: Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. INTERPRETATION: Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. FUNDING: The Rhodes Trust, Bill & Melinda Gates Foundation, the Wellcome Trust, the National Library of Medicine of the National Institutes of Health, the European Union's Horizon 2020 research and innovation programme

Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies

The PULSAR Specialist Care protocol: a stepped-wedge cluster randomized control trial a training intervention for community mental health teams in recovery-oriented practice

Background: Recovery features strongly in Australian mental health policy; however, evidence is limited for the efficacy of recovery-oriented practice at the service level. This paper describes the Principles Unite Local Services Assisting Recovery (PULSAR) Specialist Care trial protocol for a recovery-oriented practice training intervention delivered to specialist mental health services staff. The primary aim is to evaluate whether adult consumers accessing services where staff have received the intervention report superior recovery outcomes compared to adult consumers accessing services where staff have not yet received the intervention. A qualitative sub-study aims to examine staff and consumer views on implementing recovery-oriented practice. A process evaluation sub-study aims to articulate important explanatory variables affecting the interventions rollout and outcomes. Methods: The mixed methods design incorporates a two-step stepped-wedge cluster randomized controlled trial (cRCT) examining cross-sectional data from three phases, and nested qualitative and process evaluation sub-studies. Participating specialist mental health care services in Melbourne, Victoria are divided into 14 clusters with half randomly allocated to receive the staff training in year one and half in year two. Research participants are consumers aged 18-75 years who attended the cluster within a previous three-month period either at baseline, 12 (step 1) or 24 months (step 2). In the two nested sub-studies, participation extends to cluster staff. The primary outcome is the Questionnaire about the Process of Recovery collected from 756 consumers (252 each at baseline, step 1, step 2). Secondary and other outcomes measuring well-being, service satisfaction and health economic impact are collected from a subset of 252 consumers (63 at baseline; 126 at step 1; 63 at step 2) via interviews. Interview based longitudinal data are also collected 12 months apart from 88 consumers with a psychotic disorder diagnosis (44 at baseline, step 1; 44 at step 1, step 2). cRCT data will be analyzed using multilevel mixed-effects modelling to account for clustering and some repeated measures, supplemented by thematic analysis of qualitative interview data. The process evaluation will draw on qualitative, quantitative and documentary data. Discussion: Findings will provide an evidence-base for the continued transformation of Australian mental health service frameworks toward recovery

A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC

A TCR derived from a patient with relapsing-remitting multiple sclerosis engages the self-peptide myelin basic protein in the context of HLA-DQ1 in a very unusual way

The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive—despite the region’s long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000–771,000) associated with bacterial AMR and 141,000 deaths (99,900–196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000–241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200–278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600–168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000–608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen–drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen–drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen–drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.publishedVersio

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201