A robust clustering algorithm for identifying problematic samples in genome-wide association studies

Summary: High-throughput genotyping arrays provide an efficient way to survey single nucleotide polymorphisms (SNPs) across the genome in large numbers of individuals. Downstream analysis of the data, for example in genome-wide association studies (GWAS), often involves statistical models of genotype frequencies across individuals. The complexities of the sample collection process and the potential for errors in the experimental assay can lead to biases and artefacts in an individual's inferred genotypes. Rather than attempting to model these complications, it has become a standard practice to remove individuals whose genome-wide data differ from the sample at large. Here we describe a simple, but robust, statistical algorithm to identify samples with atypical summaries of genome-wide variation. Its use as a semi-automated quality control tool is demonstrated using several summary statistics, selected to identify different potential problems, and it is applied to two different genotyping platforms and sample collections

School‐based systems change for obesity prevention in adolescents: outcomes of the Australian Capital Territory ‘It's Your Move!’

Objective: The Australian Capital Territory It's Your Move!' (ACT-IYM) was a three-year (2012-2014) systems intervention to prevent obesity among adolescents. Methods: The ACT-IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12-16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school-specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric data were objectively measured and behavioural data self-reported. Results: Proportions of overweight or obesity were similar over time within the intervention (24.5% baseline and 22.8% follow-up) and comparison groups (31.8% baseline and 30.6% follow-up). Within schools, two of three the intervention schools showed a significant decrease in the prevalence of overweight and obesity (p<0.05). Conclusions: There was some evidence of effectiveness of the systems approach to preventing obesity among adolescents. Implications for public health: The incorporation of systems thinking has been touted as the next stage in obesity prevention and public health more broadly. These findings demonstrate that the use of systems methods can be effective on a small scale

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Plasma-derived immunoglobulin G (IgG) is on WHO’s Essential Medicines List, yet developing countries face severe shortages of this critical treatment. Infusion of IgG prepared from locally-collected plasma provides an advantageous mix of antibodies to viral and bacterial pathogens found in the living environment, and this can reduce recurrent infections in immune-deficient patients. We developed a simple manufacturing process using disposable equipment (blood bags, hemodialyzer, and filters) to isolate immunoglobulins from minipools of 20 plasma donations. This process yields a ca. 90% pure virally-inactivated immunoglobulin fraction at 50–60% recovery. Anti-hepatitis B and anti-rubella immunoglobulins were enriched fourfold to sixfold. The product was free of in-vitro thrombogenic and proteolytic activity, confirming its expected clinical safety profile. Virus validations showed caprylic acid treatment robustly inactivated or removed infectivity of lipid-enveloped viruses, including human immunodeficiency virus (HIV) and hepatitis C virus model. This simple and cost-effective process is implemented in Egypt to prepare experimental batches for clinical evaluation. It can enhance immunoglobulin supplies to treat immunodeficient patients through passive transmission of antibodies directed against local pathogens. The method requires minimal training and reasonable infrastructure, and is a practical means to prepare convalescent hyperimmune IgG during infectious outbreaks such as the current Ebola episode.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Evaluation of the effect of blood contamination on the compressive strength of MTA modified with hydration accelerators

Objectives This study was performed to evaluate the effect of blood contamination on the compressive strength (CS) of Root MTA (RMTA) modified with Calcium chloride (CaCl2) and Disodium hydrogen phosphate (Na2HPO4) as setting accelerators over time. Materials and Methods A total of 110 cylindrical specimens of RMTA were divided into 6 experimental groups as follows: Group1, RMTA; Group 2, RMTA modified with CaCl2 (RMTA-C); Group 3, RMTA modified with Na2HPO4 (RMTA-N); Group 4, RMTA contaminated with blood; Group 5, RMTA-C contaminated with blood; Group 6, RMTA-N contaminated with blood. The CS of specimens in all groups was evaluated after 3 hr, 24 hr, and 1 wk. In the modified groups (groups 2, 3, 5, and 6) the CS of five specimens per group was also evaluated after 1 hr. Results Blood contamination significantly reduced the CS of all materials at all time intervals (p < 0.05). After 3 hr, the CS of specimens in the RMTA groups (with and without blood contamination) was significantly lower than those in the RMTA-C and RMTA-N groups (p < 0.05). The CS values were not significantly different at the other time intervals. In all groups, the CS of specimens significantly increased over time (p < 0.05). Conclusions Blood contamination decreased the CS of both original and accelerated RMTA

Molecular detection of pathogens in ticks and fleas collected from companion dogs and cats in East and Southeast Asia

Background Ticks and fleas are considered amongst the most important arthropod vectors of medical and veterinary concern due to their ability to transmit pathogens to a range of animal species including dogs, cats and humans. By sharing a common environment with humans, companion animal-associated parasitic arthropods may potentially transmit zoonotic vector-borne pathogens (VBPs). This study aimed to molecularly detect pathogens from ticks and fleas from companion dogs and cats in East and Southeast Asia. Methods A total of 392 ticks and 248 fleas were collected from 401 infested animals (i.e. 271 dogs and 130 cats) from China, Taiwan, Indonesia, Malaysia, Singapore, Thailand, the Philippines and Vietnam, and molecularly screened for the presence of pathogens. Ticks were tested for Rickettsia spp., Anaplasma spp., Ehrlichia spp., Babesia spp. and Hepatozoon spp. while fleas were screened for the presence of Rickettsia spp. and Bartonella spp. Result Of the 392 ticks tested, 37 (9.4%) scored positive for at least one pathogen with Hepatozoon canis being the most prevalent (5.4%), followed by Ehrlichia canis (1.8%), Babesia vogeli (1%), Anaplasma platys (0.8%) and Rickettsia spp. (1%) [including Rickettsia sp. (0.5%), Rickettsia asembonensis (0.3%) and Rickettsia felis (0.3%)]. Out of 248 fleas tested, 106 (42.7%) were harboring at least one pathogen with R. felis being the most common (19.4%), followed by Bartonella spp. (16.5%), Rickettsia asembonensis (10.9%) and “Candidatus Rickettsia senegalensis” (0.4%). Furthermore, 35 Rhipicephalus sanguineus ticks were subjected to phylogenetic analysis, of which 34 ticks belonged to the tropical and only one belonged to the temperate lineage (Rh. sanguineus (sensu stricto)). Conclusion Our data reveals the circulation of different VBPs in ticks and fleas of dogs and cats from Asia, including zoonotic agents, which may represent a potential risk to animal and human health

Zoonotic Vectorborne Pathogens and Ectoparasites of Dogs and Cats in Eastern and Southeast Asia

To provide data that can be used to inform treatment and prevention strategies for zoonotic pathogens in animal and human populations, we assessed the occurrence of zoonotic pathogens and their vectors on 2,381 client-owned dogs and cats living in metropolitan areas of 8 countries in eastern and Southeast Asia during 2017-2018. Overall exposure to ectoparasites was 42.4% in dogs and 31.3% in cats. Our data cover a wide geographic distribution of several pathogens, including Leishmania infantum and zoonotic species of filariae, and of animals infested with arthropods known to be vectors of zoonotic pathogens. Because dogs and cats share a common environment with humans, they are likely to be key reservoirs of pathogens that infect persons in the same environment. These results will help epidemiologists and policy makers provide tailored recommendations for future surveillance and prevention strategies