5,592 research outputs found

    Novel methods for identification and quantification of iron fortificants in cereal flours

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    Iron deficiency is the most common nutrient deficiency globally. Fortification of cereal grains is a main strategy used to ameliorate global iron deficiency due to its safety and efficacy. For fortification to be effective, fortification programs must use appropriate iron compounds at appropriate levels. However, existing laboratory methods to identify and quantify fortificants are time consuming and costly. Our objective was to develop a quick and simple method to identify and quantify iron compounds commonly used for flour fortification. Unfortified whole wheat, refined wheat, and yellow corn flours were fortified with 20–60 mg Fe/kg flour using ferric pyrophosphate (FePP), ferrous sulfate (FeSO4), ferrous citrate (FeCit), ferrous fumarate (FeFum), sodium ferric EDTA (NaFeEDTA), and electrolytic iron (EFe). Using potassium thiocyanate (KSCN) with HCl with and without hydrogen peroxide (H2O2), we identified EFe, ferric, and ferrous fortificants. NaFeEDTA, FePP, FeSO4, FeCit, and FeFum were identified based on their solubility in water using ferrozine with and without ascorbic acid (ASC). An alternative method for identification that uses only KSCN as a chromogen was also developed but was inferior to the ferrozine method. Four blinded samples were prepared with randomly selected fortificants (EFe, NaFeEDTA, FePP, FeFum) and all were correctly identified by four personnel. For quantification, those four samples plus an additional FeSO4 sample were tested blindly. The average of each person\u27s reported iron levels for each sample were within 10 mg Fe/kg of actual iron levels 85% of the time. Estimated iron levels from the visual method were not significantly different than iron levels from two standard quantitative methods (p \u3e 0.05) for all the fortificants tested suggesting reliability of simple visual testing. These quick, inexpensive, and reliable methods will be useful for agencies to identify the type and amount of iron added to flour to monitor the quality of iron fortification strategies

    Developing a methodology for online feedback and assessment

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    It is widely accepted that when seeking to implement CAA we should not begin with the technology but with the pedagogy. If CAA is to be used appropriately it must be regarded as a range of assessment strategies, including objective tests, formative self-assessment and so on. This paper describes an action research project to develop a methodology for the implementation of online feedback and assessment. The methodology incorporates pedagogic, operational and strategic issues and is emerging as part of the continued development of CAA at Sheffield Hallam University

    Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group.

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    Genetic testing for hereditary cancer predisposition has evolved rapidly in recent years with the discovery of new genes, but there is much debate over the clinical utility of testing genes for which there are currently limited data regarding the degree of associated cancer risk. To address the discrepancies that have arisen in the provision of these tests across the UK, the UK Cancer Genetics Group facilitated a 1-day workshop with representation from the majority of National Health Service (NHS) clinical genetics services. Using a preworkshop survey followed by focused discussion of genes without prior majority agreement for inclusion, we achieved consensus for panels of cancer genes with sufficient evidence for clinical utility, to be adopted by all NHS genetics services. To support consistency in the delivery of these tests and advice given to families across the country, we also developed management proposals for individuals who are found to have pathogenic mutations in these genes. However, we fully acknowledge that the decision regarding what test is most appropriate for an individual family rests with the clinician, and will depend on factors including specific phenotypic features and the family structure

    Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

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    Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

    The biosocial genome? : Interdisciplinary perspectives on environmental epigenetics, health and society

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    In recent years, research on how the human environment and life-style influence gene expression has generated considerable scientific and public interest. Articles in prominent international newspapers with headlines such as “Why your DNA isn’t your destiny” (Time Magazine in 2010) or “Poverty leaves traces in children’s genome” (Süddeutsche Zeitung in 2016) have drawn public interest to the emerging field of environmental epigenetics. It is a sub-division of the much more heterogeneous research field of epigenetics, which aims to understand how interactions between the environment and the genome can lead to epigenetic modifications that affect gene expression. Environmental epigenetics is often heralded as providing a revolutionary perspective on disease etiology, particularly with regard to so-called ‘life-style diseases’ such as cardiovascular disease or diabetes. It is also often presented as a vital new framework for understanding differences in the susceptibility and resilience to mental illness and the long-term damaging effects of a wide variety of environmental factors. Environmental epigenetics engages with the social context of both individuals and populations. Studies investigate, for example, how socio-economic status, exercise habits, diet or experiences of trauma might influence biological processes at the molecular level. This has created great interest among social scientists and scholars in the humanities as it raises a number of questions at the intersection of the natural sciences, the social sciences and the humanities: for example, how to conceptualize the social environment in a laboratory context. To explore research areas at these intersections and assess the potential social and political implications of environmental epigenetics, international scholars from the life sciences, social sciences and humanities met in January 2017 in Munich, Germany. This article presents some of the main findings from these interdisciplinary discussions. We conclude that environmental epigenetics has great potential for elucidating how human society affects human biology, but we caution against over-simplified translations from social structures to biological processes and vice versa

    Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.

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    PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met

    Cancer Variant Interpretation Group UK (CanVIG-UK): an exemplar national subspecialty multidisciplinary network.

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    Advances in technology have led to a massive expansion in the capacity for genomic analysis, with a commensurate fall in costs. The clinical indications for genomic testing have evolved markedly; the volume of clinical sequencing has increased dramatically; and the range of clinical professionals involved in the process has broadened. There is general acceptance that our early dichotomous paradigms of variants being pathogenic-high risk and benign-no risk are overly simplistic. There is increasing recognition that the clinical interpretation of genomic data requires significant expertise in disease-gene-variant associations specific to each disease area. Inaccurate interpretation can lead to clinical mismanagement, inconsistent information within families and misdirection of resources. It is for this reason that 'national subspecialist multidisciplinary meetings' (MDMs) for genomic interpretation have been articulated as key for the new NHS Genomic Medicine Service, of which Cancer Variant Interpretation Group UK (CanVIG-UK) is an early exemplar. CanVIG-UK was established in 2017 and now has >100 UK members, including at least one clinical diagnostic scientist and one clinical cancer geneticist from each of the 25 regional molecular genetics laboratories of the UK and Ireland. Through CanVIG-UK, we have established national consensus around variant interpretation for cancer susceptibility genes via monthly national teleconferenced MDMs and collaborative data sharing using a secure online portal. We describe here the activities of CanVIG-UK, including exemplar outputs and feedback from the membership
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