Labelling Genetically Modified Products Under International Law

This paper focuses on the debate on the health, policy and legal regimes that require the special labeling of food, drugs and other products that contain genetically-modified-organisms. The paper examines national and international regulatory schemes on genetically-modified-organisms and the roles of the General Agreements on Tariffs and Trade (GATT) and World Trade Organization (WTO) conventions for non-restrictive global trade. This paper analyzes the scope, aims and objectives of the proposed international Biosafety Protocol in line with the overarching goals of GATT/WTO. The paper concludes that the food industry and individual producers should have the liberty to decide whether to label the genetically-modified products because having regulations based on consumer anxiety without any scientific evidence of harm violates the GATT objectives

Data linkage to monitor hepatitis C-associated end-stage liver disease and hepatocellular carcinoma inpatient stays in England

Persons with chronic hepatitis C (HCV) infection are at increased risk of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). The impact of hepatitis treatment scale-up and elimination strategies on ESLD and HCC incidence is a critical measure of progress towards WHO targets. Data from national laboratory surveillance of HCV diagnoses were linked to inpatient care records in Hospital Episode Statistics (HES). For persons first diagnosed with HCV between 1998-2016, we describe the characteristics of those with ESLD and HCC and estimate incidence. Of persons diagnosed with HCV between 1998 and 2016 (104,674), 9.1 % (9,525) had an admission for ESLD and 2.5% (2,610) for HCC. The majority of persons with ESLD and HCC were male (70.7% and 82.7%) and of white ethnicity (89.9% and 82.7%). Crude incidence of ESLD and HCC admission was 10.4 and 3.2 per 1,000 person years respectively. When compared to 2011-2013, incidence of ESLD and HCC admissions in 2014-2017 were lower [ESLD incidence rate ratio (IRR): 0.81; 95% Confidence interval (CI): 0.76-0.86; HCC IRR: 0.90; 95% CI: 0.82-1.00, p=0.045]. Data linkage showed considerable underreporting of HCV in HES coding for ESLD and HCC (16.0% and 11.3% respectively). In conclusion, we found a decline in incidence of ESLD and HCC-related inpatient admissions since 2011-2013. Linked analysis is required for the continued monitoring of ESLD and HCC inpatient incidence. However, HES data quality issues around completeness of identifiers contribute to uncertainty in linkage and may limit our ability to robustly monitor progress towards WHO elimination goals

Refugee and Migrant Women's Views of Antenatal Ultrasound on the Thai Burmese Border: A Mixed Methods Study

Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common.The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan : results of pre-COVID and COVID-19 lockdown stakeholder engagements

Abstract Introduction With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. Methods In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. Results Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. Conclusion Slum residents’ ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered

Paediatric acute hepatitis of unknown aetiology : a national investigation and adenoviraemia case-control study in the UK

Funding Information: This work was undertaken as part of a national enhanced incident by UK public health agencies. We thank the parents and guardians of the children who gave up their valuable time to speak to the public health investigation teams; without their support we could not have been able to undertake a thorough investigation. We are grateful to the many paediatricians and liver specialists who reported cases to us and responded to follow-up with further information. We also thank Ezra Linley and Simon Tonge of the UK Health Security Agency Seroepidemiology Unit for rapidly providing serum samples for testing. We would like to thank the Incident Management Teams of the UK nations, members of the incident cells, epidemiology, laboratory, and local Health Protection Teams who supported the investigations, in particular: Katy Sinka, Mike Gent, Suzanna Howes, Eileen Gallagher, Selene Corsini, Eleanor Clarke, Rajani Raghu, Kelsey Mowat, Iain Hayden, Matt Hibbert, Skye Firminger, Catriona Angel, Donna Haskins, Kay Ratcliffe, Hannah Emmett, Alex Elliot, Helen Hughes, Sarah Deeny, Sarah Garner, Sarah Gerver, Flora Stevens, Paula Blomquist, Gabriel Gurmail Kauffman, Kristine Cooper, Hannah Taylor, Giovanni Leonardi, Michelle Dickinson and Michelle Watson from England; Kimberly Marsh, Michael Lockhart, David Yirrell, Sandra Currie, Kate Templeton, Samantha Shepherd, Roisin Ure, Jim McMenamin, Rachel Tayler, Louisa Pollock, Antonia Ho, Chris Cunningham and Hayley Peacock from Scotland; and Katie Binley and Meg Wallace from Northern Ireland.Peer reviewe

Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose.

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p<1x10-7 (adjusted for multiple hypothesis-testing with the IBC array). Two SNPs had significant joint effects in the overall model and significant main effects only in one smoking stratum: rs140637 (FBN1) in AA individuals had a significant main effect only among smokers, and rs1444261 (closest gene C2orf63) in EA individuals had a significant main effect only among nonsmokers. Three additional SNPs were identified as having potential interaction by exhibiting a significant main effects only in smokers: rs1801232 (CUBN) in AA individuals, rs12243326 (TCF7L2) in EA individuals, and rs4132670 (TCF7L2) in EA individuals. No SNP met significance for potential interaction with smoking on baseline FG. The identification of these loci provides evidence for genetic interactions with smoking exposure that may explain some of the heterogeneity in the association between smoking and T2D

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p

Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis

10.1371/journal.pone.0053830PLoS ONE81