Implementation of a reference standard and proficiency testing programme by the World Wide Antimalarial Resistance Network (WWARN)

<p>Abstract</p> <p>Background</p> <p>The Worldwide Antimalarial Resistance Network (WWARN) is a global collaboration to support the objective that anyone affected by malaria receives effective and safe drug treatment. The Pharmacology module aims to inform optimal anti-malarial drug selection. There is an urgent need to define the drug exposure - effect relationship for most anti-malarial drugs. Few anti-malarials have had their therapeutic blood concentration levels defined. One of the main challenges in assessing safety and efficacy data in relation to drug concentrations is the comparability of data generated from different laboratories. To explain differences in anti-malarial pharmacokinetics in studies with different measurement laboratories it is necessary to confirm the accuracy of the assay methods. This requires the establishment of an external quality assurance process to assure results that can be compared. This paper describes this process.</p> <p>Methods</p> <p>The pharmacology module of WWARN has established a quality assurance/quality control (QA/QC) programme consisting of two separate components:</p> <p indent="1">1. A proficiency testing programme where blank human plasma spiked with certified reference material (CRM) in different concentrations is sent out to participating bioanalytical laboratories.</p> <p indent="1">2. A certified reference standard programme where accurately weighed amounts of certified anti-malarial reference standards, metabolites, and internal standards are sent to participating bioanalytical and in vitro laboratories.</p> <p>Conclusion</p> <p>The proficiency testing programme is designed as a cooperative effort to help participating laboratories assess their ability to carry out drug analysis, resolve any potential problem areas and to improve their results - and, in so doing, to improve the quality of anti-malarial pharmacokinetic data published and shared with WWARN.</p> <p>By utilizing the same source of standards for all laboratories, it is possible to minimize bias arising from poor quality reference standards. By providing anti-malarial drug standards from a central point, it is possible to lower the cost of these standards.</p

Cytidine and Uridine Increase Striatal CDP-Choline Levels Without Decreasing Acetylcholine Synthesis or Release

SUMMARY Aims: Treatments that increase acetylcholine release from brain slices decrease the synthesis of phosphatidylcholine by, and its levels in, the slices. We examined whether adding cytidine or uridine to the slice medium, which increases the utilization of choline to form phospholipids, also decreases acetylcholine levels and release. Methods: We incubated rat brain slices with or without cytidine or uridine (both 25-400 µM), and with or without choline (20-40 µM), and measured the spontaneous and potassium-evoked release of acetylcholine. Results: Striatal slices stimulated for 2 h released 2650 ± 365 pmol of acetylcholine per mg protein when incubated without choline, or 4600 ± 450 pmol/mg protein acetylcholine when incubated with choline (20 µM). Adding cytidine or uridine (both 25-400 µM) to the media failed to affect acetylcholine release whether or not choline was also added, even though the pyrimidines (400 µM) did enhance choline`s utilization to form CDP-choline by 89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine release from hippocampal and cortical slices. Cytidine or uridine also failed to affect acetylcholine levels in striatal slices, nor choline transport into striatal synaptosomes. Conclusion: These data show that cytidine and uridine can stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis or release

Classification of crystallization outcomes using deep convolutional neural networks

The Machine Recognition of Crystallization Outcomes (MARCO) initiative has assembled roughly half a million annotated images of macromolecular crystallization experiments from various sources and setups. Here, state-of-the-art machine learning algorithms are trained and tested on different parts of this data set. We find that more than 94% of the test images can be correctly labeled, irrespective of their experimental origin. Because crystal recognition is key to high-density screening and the systematic analysis of crystallization experiments, this approach opens the door to both industrial and fundamental research applications

An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt.

BACKGROUND: Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further. METHODS: We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children; N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS). RESULTS: The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = - 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (Nagelkerke R2 0.022, p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R2 0.010, p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt. CONCLUSIONS: Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected

Atopic dermatitis and food sensitization in South African toddlers: Role of fiber and gut microbiota

The pathogenesis of atopic dermatitis (AD) is complex and related to allergic responses and defects in skin barrier function. In common with many atopic diseases, the prevalence of AD has been increasing across the world.1 One of the theories for this increase is increased hygiene and urbanization-related changes in the environment, which can affect the human microbiome.2 Previous studies have found associations between the composition of the early gut microbiome and development of atopic conditions, including AD.3 Although the rate of atopic conditions, including AD and food allergy, is increasing on all continents, the prevalence of these diseases is still lower in African countries.1 This is especially interesting because individuals of African origin who live in Western countries, such as African Americans, are at a higher risk for severe AD.4 This variation places Africa in a special position; studying African populations is necessary not only to find ways to prevent increases of allergy conditions in African countries but also to provide important clues to the causes of this global increasing of allergic conditions. Young children who have developed AD in African communities with a low incidence of atopic disease might be the transitional group. In the current study, we have, for the first time to our knowledge, analyzed the fecal microbiota composition of a group of young black African children aged 12 to 36 months old with and without AD living in the same community in Cape Town, South Africa. Our primary goal was to examine whether toddlers with AD and control toddlers from Cape Town have different microbiomes in terms of bacterial richness and diversity. We also aimed to investigate the differences in the relative abundance for different operational taxonomic units between these 2 groups. In our subgroup analyses, we further tested the effect of multiple environmental factors on the gut microbiome in these children

Alumni Association Bulletin of the School of Nursing, 1976

Alumni Calendar The President\u27s Message Officers and Chairpersons of Committees Financial Report Annual Reports New Surgical Concept for Laryngeal Cancer Computerized Transaxial X-ray Scanner Dental Health Center The Winged Ox of St. Luke Pictures - New Building Committee Reports Resume of Alumni Minutes Ways and Means Report Alumni News Class News Names and Addresses of 1976 Graduates School of Nursing 1976 Awards Marriages Births In Memoriam - List of Alumni In Memoriam - Dr. Peter A. Herbut In Memoriam - Miss Katherine Childs Change of Address Notice Notice

RESEARCH Open Access

Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australi

An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt

Abstract: Background: Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further. Methods: We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children; N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS). Results: The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = − 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (Nagelkerke R2 0.022, p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R2 0.010, p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt. Conclusions: Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected

Fetal alcohol spectrum disorder: development of concensus referral criteria for specialist diagnostic assessment in Australia

Background: Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. Method: An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed.Results: Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities .Conclusion: Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia