HECTD2 Is Associated with Susceptibility to Mouse and Human Prion Disease

Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods

Breast-Feeding and Childhood-Onset Type 1 Diabetes:A pooled analysis of individual participant data from 43 observational studies

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSION The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies

Learning to discuss safety within the European seaweed aquaculture sector

Seaweed is seen as a promising future source of biomass, and significant efforts are taken to upscale seaweed aquaculture production in Europe. Despite regulatory frameworks for food safety, environmental safety, and occupational health and safety applicable to seaweed production, a major barrier to upscaling production is the lack of commonly accepted, uniform frameworks for safety assessment. As a consequence, efforts to deal with food safety, environmental safety, and occupational health and safety are fragmented. Based on a literature review and consultations with stakeholders, this paper introduces a generic protocol on how to approach safety of the production of seaweed. A prototype version of the generic protocol was evaluated in a practical setting in Norway. Results show that a consistent, structured approach to safety makes it possible to identify hazards and prioritize and collect data on key hazards. The protocol facilitated a sector discussion on safety, providing a shared discourse to talk about safety. It must be acknowledged that the farming and processing practices and the location of cultivation strongly influence which hazards are most relevant. The protocol succeeded in bringing focus to data collection, putting effort into the analysis of hazards considered most relevant in a practical setting

High velocity solid particle erosion behaviour of CVD boron carbide on tungsten carbide

The superior mechanical properties of boron carbide (B13C2 phase) make it an attractive candidate for application as a wear resistant coating in tribological applications. The present work aims to determine the solid particle erosion behaviour of 12�18 ?m thick CVD boron carbide coatings on cemented tungsten carbide substrates. The erosion tests were performed on a high-energy air solid particle erosion rig using 150�420 ?m spherical soda-lime glass beads and 90�355 ?m angular quartz silica sand under normal impact, at impingement velocities between 132 and 250 m s?1 and a flux rate of 0.5 kg m?2 s?1. The erosion rates and mechanisms are presented and discussed in terms of coating thickness, particle velocity, particle shape and size. The eroded surfaces were examined using 2- and 3D white light optical interferometry profiling and scanning electron microscopy (SEM) with EDS mapping to investigate the erosive wear damage mechanisms of the CVD boron carbide. The nature of post-test erodent fracture was determined using laser diffraction particle size analysis. The results indicate that erosion of CVD boron carbide occurs predominantly through a single-stage mechanism by the formation of lateral�radial crack systems that propagate outwards towards the free CVD surface and extend into the coating substrate interface. This was confirmed by optical depth profiling and from the presence of substrate and interlayer peaks in the EDS map from the vertex of the radial�lateral crack systems. The damage mechanism observed appears to be independent of the erodent shape. Adjacent lateral cracks intersect, resulting in further material loss as erosion progresses. The density of the lateral�radial crack systems is higher at the centre of the wear scar compared to the outer regions. Similar failure mechanisms for brittle coatings have recently been predicted through fracture mechanics considerations and also observed experimentally by other authors. Some evidence of surface micro- and nanochipping is also observed in other regions of the eroded CVD boron carbide surface. Comparisons have been made with previous investigations into the erosion behaviour of CVD diamond coatings under similar test conditions

Misunderstanding the Female Athlete Triad: Refuting the IOC Consensus Statement on Relative Energy Deficiency in Sport (RED-S)

We are concerned that readers of the IOC paper will be confused and misled by the poorly referenced statements and frank (and sometimes dangerous) errors in the paper. The IOC authors should publish a correction of these and other errors noted. Broadening research of low energy availability in other groups, such as the male athlete, athletes of diverse ethnicities and the disabled athlete may help to advance science and may one day warrant introduction of a specific term for whatever serious clinical sequelae of energy deficiency may be discovered in future research on men. Research on the “Female Athlete Triad” has forged a platform from which a broad array of healthcare providers (e.g., physicians, sport dietitians, mental health professionals and athletic trainers) have made great strides in learning how to manage and treat affected women. Research on the “Female Athlete Triad” has also been translated to the lay public such that more and more affected female athletes and exercising women willingly seek education, prevention and treatment. Meanwhile, subsuming the term “Female Athlete Triad” under the umbrella of the term RED-S has the potential to confuse rather than enlighten, and undo decades of work educating and advocating for awareness, prevention and treatment for the Triad. The individual most impacted by the de-emphasis on the Triad will be the female athlete herself. The overwhelming clinical importance of the Female Athlete Triad compared with other conditions under the proposed RED-S umbrella will continue to make a specific reference for the Triad useful for those who deal with it, including physicians, coaches, sport dietitians, athletics trainers, parents and, most importantly, female athletes. As such, efforts promoting awareness, prevention and treatment of the Female Athlete Triad remain critically important and should not be overshadowed by an ill-conceived and poorly defended new construct

Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies

WSTĘP. Celem badania było sprawdzenie, czy u dzieci urodzonych przez starsze matki występuje większe ryzyko zachorowania na cukrzycę typu 1, poprzez łączną analizę wcześniejszych badań z użyciem indywidualnych danych pacjentów dla skorygowania względem znanych czynników błędu. MATERIAŁ I METODY. Odpowiednie badania, opublikowane przed czerwcem 2009 roku, zostały zidentyfikowane w bazach MEDLINE, Web of Science i EMBASE. Skontaktowano się z autorami analiz i poproszono o dostarczenie indywidualnych danych pacjentów lub przeprowadzenie wcześniej określonych analiz. Dla każdej z analiz oszacowano ryzyko wystąpienia cukrzycy typu 1 względem wieku matki zarówno przed, jak i po uwzględnieniu potencjalnych czynników błędu. W celu uzyskania złożonych ilorazów szans i zbadania różnic między badaniami zastosowano metody oparte na metaanalizie. WYNIKI. Dostępne dane pochodziły z 5 badań kohortowych i 25 badań porównawczych, obejmujących 14 724 przypadki cukrzycy typu 1. Ogółem, prawdopodobieństwo wystąpienia cukrzycy typu 1 w dzieciństwie wzrosło średnio o 5% (95% CI 2–9) na każde 5 lat wieku matki (p = 0,006), ale wyniki badań nie były jednorodne (niejednorodność I2 = 70%). W badaniach z małym ryzykiem błędu wyraźnie było widać wzrost szans na wystąpienie cukrzycy — 10% na każde 5 lat wieku matki. Uwzględnienie potencjalnych czynników błędu tylko nieznacznie wpłynęło na te szacunki. WNIOSKI. Wykazano niewielki, ale istotny, liniowy wzrost ryzyka występowania dziecięcej cukrzycy typu 1 wraz z wiekiem matki, ale siła tego skojarzenia różniła się między badaniami. Niewielki odsetek przypadków wzrostu występowania dziecięcej cukrzycy typu 1 w ostatnich latach można by wytłumaczyć rosnącym wiekiem matek. (Diabet. Prakt. 2010; 11, 5: 181–193)OBJECTIVE. The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. MATERIAL AND METHODS. Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS. Data were available for 5 cohort and 25 casecontrol studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2–9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS. There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age. (Diabet. Prakt. 2010; 11, 5: 181–193