A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: The ANU-ADRI

Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up. © 2014 Anstey et al

Safety Profile of L-Arginine Infusion in Moderately Severe Falciparum Malaria

BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in adults with moderately severe malaria. METHODOLOGY AND FINDINGS: In an ascending dose study, adjunctive intravenous L-arginine hydrochloride was infused over 30 minutes in doses of 3 g, 6 g and 12 g to three separate groups of 10 adults hospitalized with moderately severe Plasmodium falciparum malaria in addition to standard quinine therapy. Symptoms, vital signs and selected biochemical measurements were assessed before, during, and for 24 hours after infusion. No new or worsening symptoms developed apart from mild discomfort at the intravenous cannula site in two patients. There was a dose-response relationship between increasing mg/kg dose and the maximum decrease in systolic (ρ = 0.463; Spearman's, p = 0.02) and diastolic blood pressure (r = 0.42; Pearson's, p = 0.02), and with the maximum increment in blood potassium (r = 0.70, p<0.001) and maximum decrement in bicarbonate concentrations (r = 0.53, p = 0.003) and pH (r = 0.48, p = 0.007). At the highest dose (12 g), changes in blood pressure and electrolytes were not clinically significant, with a mean maximum decrease in mean arterial blood pressure of 6 mmHg (range: 0–11; p<0.001), mean maximal increase in potassium of 0.5 mmol/L (range 0.2–0.7 mmol/L; p<0.001), and mean maximal decrease in bicarbonate of 3 mEq/L (range 1–7; p<0.01) without a significant change in pH. There was no significant dose-response relationship with blood phosphate, lactate, anion gap and glucose concentrations. All patients had an uncomplicated clinical recovery. CONCLUSIONS/SIGNIFICANCE: Infusion of up to 12g of intravenous L-arginine hydrochloride over 30 minutes is well tolerated in adults with moderately severe malaria, with no clinically important changes in hemodynamic or biochemical status. Trials of adjunctive L-arginine can be extended to phase 2 studies in severe malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT0014736

Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.&lt;p&gt;&lt;/p&gt; Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (&#8804;13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was &#60;8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.&lt;p&gt;&lt;/p&gt; Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.&lt;p&gt;&lt;/p&gt

Northern winter climate change: assessment of uncertainty in CMIP5 projections related to stratosphere-troposphere coupling

Journal ArticlePublished versionFuture changes in the stratospheric circulation could have an important impact on northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric circulation variations but also to vertically coherent variations in troposphere-stratosphere circulation. Here we assess northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) multimodel ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a signi fi cant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification, and the stratospheric wind change on SLP. We find that the intermodel spread in stratospheric wind change contributes substantially to the intermodel spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Sex and gender differences in risk scores for dementia and Alzheimer's disease among cisgender, transgender, and non-binary adults

INTRODUCTION: Few studies have explored dementia risk according to sex and gender including for transgender and non-binary adults. This study evaluated dementia risk factors and risk scores among cisgender, transgender, and non-binary adults. METHODS: Observational data were drawn from the 2019 Behavioral Risk Factor Surveillance System. A matched-cohort approach was used to develop sex (male, female) and gender identity cohorts (cisgender men, cisgender women, transgender men, transgender women, and non-binary adults) for comparison. Dementia risk scores were calculated using established mid-life and late-life risk score algorithms. RESULTS: Males had higher overall mid-life dementia risk, and lower late-life Alzheimer's disease risk compared to females. Transgender men, transgender women, and non-binary adults had higher overall late-life risk compared to both cisgender men and women. DISCUSSION: Future research is needed to build the evidence base for specific risk factors that may be contributing to higher overall risk among understudied and underserved gender groups. Highlights: Using data from the 2019 Behavioral Risk Factor Surveillance System, this matched-cohort study found that those assigned female at birth had lower overall mid-life dementia risk and higher overall late-life Alzheimer's disease (AD) risk compared to those assigned male at birth. Transgender men, transgender women, and non-binary adults all showed higher overall late-life AD risk compared to cisgender men and cisgender women. Between-group differences were found in the incidence of specific risk and protective factors for dementia and AD

Summary and Highlights of the SPARC-Reanalysis Intercomparison Project

The climate research community uses global atmospheric reanalysis data sets to understand a wide range of processes and variability in the atmosphere; they are a particularly powerful tool for studying phenomena that cannot be directly observed. Different reanalyses may give very different results for the same diagnostics. The Stratosphere troposphere Processes And their Role in Climate (SPARC) Reanalysis Intercomparison Project (S-RIP) is a coordinated activity to compare key diagnostics that are important for stratospheric processes and their tropospheric connections among available reanalyses. S-RIP has been identifying differences among reanalyses and their underlying causes, providing guidance on appropriate usage of reanalysis products in scientific studies (particularly those of relevance to SPARC), and contributing to future improvements in the reanalysis products by establishing collaborative links between reanalysis centres and data users. S-RIP emphasizes diagnostics of the upper troposphere, stratosphere, and lower mesosphere. The draft S-RIP final report is expected to be completed in 2018. This poster gives a summary of the S-RIP project and presents highlights including results on the Brewer-Dobson circulation, stratosphere/troposphere dynamical coupling, the extra-tropical upper troposphere / lower stratosphere, the tropical tropopause layer, the quasi-biennial oscillation, lower stratospheric polar processing, and the upper stratosphere/lower mesosphere