Extended duration of the detectable stage by adding HPV test in cervical cancer screening

The human papillomavirus test (HPV) test could improve the (cost-) effectiveness of cervical screening by selecting women with a very low risk for cervical cancer during a long period. An analysis of a longitudinal study suggests that women with a negative Pap smear and a negative HPV test have a strongly reduced risk of developing cervical abnormalities in the years following the test, and that HPV testing lengthens the detectable stage by 2-5 years, compared to Pap smear detection alone

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

The effectiveness of e-Learning on biosecurity practice to slow the spread of invasive alien species

Online e-Learning is increasingly being used to provide environmental training. Prevention measures including biosecurity are essential to reducing the introduction and spread of invasive alien species (IAS) and are central to international and national IAS policy. This paper is the first to evaluate the effectiveness of e-Learning as a tool to increase awareness, risk perception and biosecurity behaviour in relation to IAS among individuals conducting work activities or research (fieldwork) in the field. We surveyed participants (a mixture of students and professionals) before, and 6 months after undertaking an e-Learning course on IAS and biosecurity practices. Awareness of IAS and self-reported biosecurity behaviour increased after e-Learning among students and professionals. Students had a lower awareness of IAS than professionals before training (20% of students vs 60% of professionals), but after training students showed a greater increase in awareness which led to similar levels of awareness post-training (81%). Prior to training, risk perception was also lower amongst students than professionals (33% of students and 59% of professionals were aware of the risk that their activities posed to the accidental spread of IAS). There was no change in risk perception amongst professionals after training, however training led to a doubling of risk perception in students. E-Learning also led to an increase in reported biosecurity behaviour and cleaning practices and there were higher levels of biosecurity cleaning amongst professionals. The higher awareness and better biosecurity amongst professionals is likely to reflect their familiarity with the issues of IAS and day-to-day activities in the field. Our results suggest that e-Learning is an effective tool to raise awareness and encourage behaviour change among field workers and researchers in an attempt to reduce the risk of accidental introduction and spread of IAS

Trends in all cause and viral liver disease-related hospitalizations in people with hepatitis B or C: a population-based linkage study

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported an excess burden of cancer and mortality in populations with chronic hepatitis B (HBV) or C (HCV), but there are limited data comparing hospitalization rates. In this study, we compared hospitalization rates for all causes and viral liver disease in people notified with HBV or HCV in New South Wales (NSW), Australia.</p> <p>Methods</p> <p>HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends.</p> <p>Results</p> <p>The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend.</p

A Randomized Controlled Phase IIb Trial of Antigen-Antibody Immunogenic Complex Therapeutic Vaccine in Chronic Hepatitis B Patients

BACKGROUND: The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed. METHODS AND PRINCIPAL FINDINGS: Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8% (17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05). CONCLUSIONS: Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-00000022

Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease

Background: Pediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders. Methodology/Principal Findings: We applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity). Conclusions/Significance: Microbiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.Natural Sciences and Engineering Research Council of Canada (Award NSERC PGS D)National Institutes of Health (U.S.) (1-R21-A1084032-01A1

Provenancing Archaeological Wool Textiles from Medieval Northern Europe by Light Stable Isotope Analysis (δ13C, δ15N, δ2H)

We investigate the origin of archaeological wool textiles preserved by anoxic waterlogging from seven medieval archaeological deposits in north-western Europe (c. 700-1600 AD), using geospatial patterning in carbon (δ13C), nitrogen (δ15N) and non-exchangeable hydrogen (δ2H) composition of modern and ancient sheep proteins. δ13C, δ15N and δ2H values from archaeological wool keratin (n = 83) and bone collagen (n = 59) from four sites were interpreted with reference to the composition of modern sheep wool from the same regions. The isotopic composition of wool and bone collagen samples clustered strongly by settlement; inter-regional relationships were largely parallel in modern and ancient samples, though landscape change was also significant. Degradation in archaeological wool samples, examined by elemental and amino acid composition, was greater in samples from Iceland (Reykholt) than in samples from north-east England (York, Newcastle) or northern Germany (Hessens). A nominal assignment approach was used to classify textiles into local/non-local at each site, based on maximal estimates of isotopic variability in modern sheep wool. Light element stable isotope analysis provided new insights into the origins of wool textiles, and demonstrates that isotopic provenancing of keratin preserved in anoxic waterlogged contexts is feasible. We also demonstrate the utility of δ2H analysis to understand the location of origin of archaeological protein samples