Sekvensanalyse av PRV-1-isolater fra tidsrommet da HSMB brøt ut i Norge

Piscine orthoreovirus-1 (PRV-1) is the causative agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon, first described in Norway in 1999. Not all infected fish develop HSMI, and the virus has been revived from archived samples dating back to 1988, leading to a hypothesis that viral evolution has generated new genotypes with increased virulence contributing to disease development. The objective was to identify PRV-1 isolates present in Norwegian farmed salmon in the years before and after 1999. Archived samples from Norwegian farmed salmon, comprising 204 samples from 1987-2008, were screened for PRV- 1. Coding sequences were obtained for segment S1, S4, M2, L1 and L2, putatively linked to virulence, from six isolates. Phylogenetic analysis and genogrouping was performed. Screening displayed that PRV-1 was common in farmed salmon predating the first described HSMI- outbreak, and sequence analysis demonstrated a mixture of assumed high and low virulent isolates following 1999. Coinfection with isolates belonging to different phylogenetic groups was demonstrated in two fish from 1998 and 2005. Co-infection is a prerequisite for reassortment, linked to the hypothesis of the origin of the high virulent strains through evolution. In the presumed receptor binding protein σ1, a new amino acid change was discovered (E254K).Piscine orthoreovirus-1 (PRV-1) er årsaken til hjerte- og skjelettmuskelbetennelse (HSMB) hos oppdrettslaks, først beskrevet i Norge i 1999. Alle PRV-1-infiserte fisk utvikler imidlertid ikke HSMB og viruset har blitt detektert helt tilbake til 1988, som har ført til en hypotese om at viral evolusjon har generert nye genotyper med økt virulens som har bidratt til sykdomsutvikling. Hovedmålet med studien var å kartlegge genomet til PRV-1-isolater før og etter første beskrevne HSMB-utbrudd. 204 arkiverte prøver fra norsk oppdrettslaks fra 1987-2008 ble screenet for PRV-1. Kodende sekvens ble sekvensert for segment S1, S4, M2, L1 og L2, antatt koblet til virulens, fra seks isolater. Fylogenetisk analyse og genogruppering ble utført. Screeningen viste at PRV-1 var et vanlig forekommende virus hos oppdrettslaks allerede før det første beskrevne HSMB-utbruddet og sekvensanalysen demonstrerte en blanding av antatt høyvirulente og lavvirulente isolater i tidsperioden etter 1999. Studien påviste også koinfeksjon med to isolater tilhørende ulike fylogenetiske grupper hos to fisk, fra 1998 og 2005. Koinfeksjon er en forutsetning for reassortering, som knyttes til hypotesen om at høyvirulente stammer har oppstått gjennom reassortering av ulike lavvirulente stammer. I det antatt reseptorbindende proteinet σ1 ble det oppdaget en ny aminosyreendring (E254K

Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design: We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results: Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions: Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD

Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic. Graphical Abstract: (Figure presented.)Peer reviewe

"¡Cáncer es una mujer pegada como una sanguijuela sesenta años succionándole el alma!" : Un examen de los rasgos misóginos en la novela El desbarrancadero de Fernando Vallejo

El desbarrancadero, published in 2001 by Colombian author Fernando Vallejo is foremost a moving story about brotherly love, but it is also a highly critical novel that lashes out on a number of phenomena such as the catholic church, the Pope and the very idea of religion. It also addresses the poverty of Colombia, its corrupt politicians, the drug trade, viral diseases and animal abuse to mention a few more subjects. This essay however, does not aim to explore any of the above mentioned matters but rather examine how women are portrayed in this novel. The objective of this investigation, based on feminist theories, is to establish the very clear presence of misogyny attitudes

"¡Cáncer es una mujer pegada como una sanguijuela sesenta años succionándole el alma!" : Un examen de los rasgos misóginos en la novela El desbarrancadero de Fernando Vallejo

El desbarrancadero, published in 2001 by Colombian author Fernando Vallejo is foremost a moving story about brotherly love, but it is also a highly critical novel that lashes out on a number of phenomena such as the catholic church, the Pope and the very idea of religion. It also addresses the poverty of Colombia, its corrupt politicians, the drug trade, viral diseases and animal abuse to mention a few more subjects. This essay however, does not aim to explore any of the above mentioned matters but rather examine how women are portrayed in this novel. The objective of this investigation, based on feminist theories, is to establish the very clear presence of misogyny attitudes

Så mycket träning – men var tog maten vägen? En undersökning om ett kvinnligt elithandbollslags kostvanor

Att träningen har stor betydelse för en elitidrottare är en självklarhet, men får kosten lika stort utrymme? I litteratur poängteras att det måste finnas en balans mellan träning, kost och vila för att maximal träningseffekt ska kunna uppnås. Även Sveriges Olympiska Kommitté, SOK, betonar hur viktig kosten är för idrottaren och har därför utformat kostrekommendationer till elitidrottare. För att se hur SOK: s rekommendationer tillämpas i praktiken valde vi att undersöka ett kvinnligt elithandbollslags kostvanor. Vi fokuserade främst på att granska deras energiintag och energifördelning för att sedan kunna jämföra detta med SOK: s rekommendationer. Studien bestod av ett elithandbollslag från Västsverige där 15 spelare ingick. I undersökningen användes två kvantitativa metoder och en kvalitativ, enkätundersökning, kostundersökning och uppföljningsintervju. Med enkätundersökningen ville vi ta reda på vad spelarna kunde om kost för idrottare, medan kostundersökningen användes för att visa spelarnas kostintag. Uppföljningsintervjun tillämpades för att kontrollera att informationen vi fick ut av kostundersökningen motsvarade vad spelarna normalt åt. I denna intervju fick vi även fram vad eventuella felkällor i kostundersökningen kunde bero på. Resultatet av enkäterna antydde att det fanns bristfälliga kunskaper om kost för idrottare hos de flesta av spelarna i laget. Även kostundersökningen tydde på otillräckliga kunskaper då spelarna överlag hade för lågt energiintag i jämförelse med SOK: s rekommendationer. Däremot såg energifördelningen relativt bra ut bortsett från att spelarnas proteinintag var något högt