HPV16 Seropositivity and Subsequent HPV16 Infection Risk in a Naturally Infected Population: Comparison of Serological Assays

Background: Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays. Methodology/Principal Findings Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27–0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28–0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection. Conclusions/Significance: Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.Other Research Uni

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort

Background: Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods: The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m(2) or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results: At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th-75th percentile: 6.8-7.9 %), equalling 53 mmol/mol (51, 63);24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m(2), 95 % CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions: Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels

Pest categorisation of Lepidosaphes pistaciae

Following the commodity risk assessment of Prunus persica and P. dulcis plants for planting from Türkiye, in which Lepidosaphes pistaciae (Hemiptera: Diaspididae), the pistachio oyster scale or yellow pistachio scale, was identified as a pest of possible concern, the EFSA Panel on Plant Health performed a pest categorisation for the territory of the European Union (EU). L. pistaciae is reported as a polyphagous pest which, however, mainly affects plants of the genus Pistacia. Originating from Asia, it is widely distributed in pistachio producing countries of Central, South and West Asia. Within the EU, the pest has been reported from Cyprus and Greece. However, its precise distribution within Cyprus and Greece is unknown. It completes two generations per year and overwinters as a fully developed adult female. The eggs are hidden under the female's body and hatch around April. First-instar nymphs, crawlers, move on host plants for a short period of time before becoming permanently settled and initiating feeding, mainly on leaves but also on branches and fruits. Young females appear in early June and mature ones in late June. Plants for planting and fruits provide potential pathways for entry into the EU. Climate suitability suggests that it could further establish in large parts of the EU. In Iran, L. pistaciae is considered a devastating pest for cultivated pistachio. L. pistaciae was detected in Greece over 30 years ago with small population densities and without any records of damage. It was also found in Cyprus in 1967 and nowadays is not considered a major pest. Its ability to cause an impact in the EU is uncertain considering the lack of evidence on impact in Cyprus and Greece. Phytosanitary measures are available to reduce the likelihood of entry. While the fulfilment of the criterion on having an economic or environmental impact in the EU is associated with a key uncertainty, all the other criteria assessed by EFSA for consideration as a potential quarantine pest are met

Commodity risk assessment of Betula pendula and Betula pubescens plants from the UK

: The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as 'High risk plants, plant products and other objects'. This Scientific Opinion covers plant health risks posed by plants of Betula pendula and B. pubescens imported from the United Kingdom (UK) taking into account the available scientific information, including the technical information provided by the UK. The commodities were grouped in the risk assessment as (a) bundles of 10-20 graftwood/budwood (up to 1-year-old), (b) bare root plants which include bundles of 25 or 50 seedlings or transplants (1-2 years-old), bundles of 5, 10 or 15 whips (1-2 years-old) and single bare root plants (1-7 years-old), (c) plants in pots which include bundles of 5 and 10 cell-grown plants (1-2 years-old) and rooted plants in pots (1-7 years-old), and (d) large specimen trees up to 15-years-old. All pests associated with the commodities were evaluated against specific criteria for their relevance for this opinion. Two EU quarantine pests i.e. Meloidogyne fallax and Phytophthora ramorum (non-EU isolates) and two protected zone quarantine pests i.e. Entoleuca mammata and Thaumetopoea processionea fulfilled all relevant criteria and were selected for further evaluation. For the selected pests, the risk mitigation measures described in the technical dossier from the UK were evaluated considering the possible limiting factors. For these pests an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. In the assessment of risk, the age of the plants was considered, as larger trees are more likely to be infested mainly due to longer time grown in the field. In addition, larger canopies and root systems are more difficult to inspect, thereby making the detection of pests more challenging on large trees. The likelihood of pest freedom varies among the pests evaluated, with M. fallax being the pest most frequently expected on the imported plants. The Expert Knowledge Elicitation (EKE) indicated with 95% certainty that between 9735 and 10,000 per 10,000 large specimen trees will be free from M. fallax

Commodity risk assessment of debarked conifer wood chips fumigated with sulfuryl fluoride from the US

The European Commission requested the EFSA Panel on Plant Health to deliver a risk assessment on the likelihood of pest freedom from regulated EU quarantine pests, with emphasis on Bursaphelenchus xylophilus and its vectors Monochamus spp. of debarked conifer wood chips fumigated with sulfuryl fluoride as proposed by the United States (US) and as outlined in ISPM 28 - PT23 of sulfuryl fluoride (SF) fumigation treatment for nematodes and insects in debarked wood. The assessment considered the different phases in the wood chips' production, with special emphasis on the SF treatment. In addition to B. xylophilus and its vectors Monochamus spp., 22 EU quarantine pests and protected zone quarantine pests, some of which are regulated as groups of pests by the Commission Implementing Regulation (EU) 2019/2072, are present in the US and are potentially associated with the commodity. For these pests an expert judgement is given on the likelihood of pest freedom taking into consideration the available scientific information and technical information provided by the US, including uncertainties associated with the assessment. The likelihood of pest freedom varies among the pests evaluated, with B. xylophilus being the pest most frequently expected on the commodity. The Expert Knowledge Elicitation (EKE) indicated with 95% certainty that between 9491 and 10,000 m3 of debarked conifer wood chips treated with SF per 10,000 m3 will be free from B. xylophilus, and that between 9987 and 10,000 m3 of wood chips per 10,000 m3 will be free from Monochamus spp. Technical elements which are critical for a successful treatment and for minimising the presence of Union quarantine pests on the commodity are identified and described in the opinion. In particular, it is important to note that SF treatments are generally less effective in eliminating fungi than insects, the required parameters of the fumigation should be met at all points of the pile of wood chips and the time of storage of wood chips before treatment should be kept as short as possible because B. xylophilus can easily reproduce and spread throughout the pile under conducive conditions