Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Research to policy and practice change:is capacity building in operational research delivering the goods?

OBJECTIVES: Between 2009 and 2012, eight operational research capacity building courses were completed in Paris (3), Luxembourg (1), India (1), Nepal (1), Kenya (1) and Fiji (1). Courses had strict milestones that were subsequently adopted by the Structured Operational Research and Training InitiaTive (SORT IT) of the World Health Organization. We report on the numbers of enrolled participants who successfully completed courses, the number of papers published and their reported effect on policy and/or practice.DESIGN: Retrospective cohort study including a survey.METHODS: Participant selection criteria ensured that only those proposing specific programme-related and relevant operational research questions were selected. Effects on policy and/or practice were assessed in a standardised manner by two independent reviewers.RESULTS: Of 93 enrolled participants from 31 countries (14 in Africa, 13 in Asia, two in Latin America and two in South Pacific), 83 (89%) completed their courses. A total of 96 papers were submitted to scientific journals of which 89 (93%) were published and 88 assessed for effect on policy and practice. There was a reported effect in 65 (74%) studies including changes to programme implementation (27), adaptation of monitoring tools (24) and changes to existing guidelines (20).CONCLUSION: Three quarters of published operational research studies from these structured courses had reported effects on policy and/or practice. It is important that this type of tracking becomes a standard component of operational research and research in general.</p

End of Intensive phase treatment outcomes of hospitalized MDR–TB patients in Nigeria July 2010 – October, 2012.

<p>End of Intensive phase treatment outcomes of hospitalized MDR–TB patients in Nigeria July 2010 – October, 2012.</p

Figure 2

<p><b>a</b>. Time to sputum smear conversion among hospitalized MDR-TB patients stratified by HIV-status in Nigeria, July 2010 – October 2012. <b>b</b>.Time to culture conversion among hospitalized MDR-TB patients stratified by HIV-status in Nigeria, July 2010 – October 2012.</p

Survival among hospitalized MDR-TB patients stratified by HIV-status in Nigeria, July 2010 – October 2012.

<p>Survival among hospitalized MDR-TB patients stratified by HIV-status in Nigeria, July 2010 – October 2012.</p

Demographic and clinical characteristics of hospitalized MDR-TB patients in Nigeria, July 2010-October 2012.

<p>Demographic and clinical characteristics of hospitalized MDR-TB patients in Nigeria, July 2010-October 2012.</p

High attrition among HIV-infected patients with advanced disease treated in an intermediary referral center in Maputo, Mozambique

Background : In Mozambique, antiretroviral therapy (ART) scale-up has been successfully implemented. However, attrition in care remains a major programmatic challenge. In 2009, an intermediary-level HIV referral center was created in Maputo to ensure access to specialized care for HIV-infected patients with complications (advanced clinical-immunological stage, Kaposi sarcoma, or suspected ART failure). Objective : To determine the attrition from care and to identify risk factors that lead to high attrition among patients referred to an intermediary-level HIV referral center. Design : This was a retrospective cohort study from 2009 to 2011. Results : A total of 1,657 patients were enrolled, 847 (51%) were men, the mean age was 36 years (standard deviation: 11), the mean CD4 count was 27 cells/µl (interquartile range: 11-44), and one-third were severely malnourished. The main reasons for referral were advanced clinical stages (WHO stages 3 and 4, and CD4 count <50 cells/µl) in 70% of the cases, and 19% had Kaposi sarcoma. The overall attrition rate was 28.7 per 100 person-years (PYs) - the mortality rate was 5.0 (95% confidence interval [CI]: 4.2-5.9) per 100 PYs, and the loss-to-follow-up rate was 23.7 (95% CI: 21.9-25.6) per 100 PYs. There were 793 attritions - 137 deaths and 656 lost to follow-up (LTFU); 77% of all attrition happened within the first year. The factors independently associated with attrition were male sex (adjusted hazard ratio [aHR]: 1.15, 95% CI: 1.0-1.3), low body mass index (aHR: 1.51, 95% CI: 1.2-1.8), WHO clinical stage 3 or 4 (aHR: 1.30, 95% CI: 1.0-1.6; and aHR: 1.91, 95% CI: 1.4-2.5), later year of enrollment (aHR 1.61, 95% CI 1.3-1.9), and 'being already on ART' at enrollment (aHR 13.71, 95% CI 11.4-16.4). Conclusions : Attrition rates among HIV-infected patients enrolled in an intermediary referral center were high, mainly related to advanced stage of clinical disease. Measures are required to address this, including innovative strategies for HIV-testing uptake, earlier ART initiation and nutritional supplementation, and special attention to men and those who are already on ART at enrolment. Qualitative research is required to understand the reasons for being LTFU and design informed evidence-based interventions

Intensive-Phase Treatment Outcomes among Hospitalized Multidrug-Resistant Tuberculosis Patients: Results from a Nationwide Cohort in Nigeria

Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6-8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them