New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

PAPPA PÅ ANSTALT– En kvalitativ studie med åtta fäder på anstalt, om deras tankar och upplevelser kring sina barn

Uppsatsens syfte är att undersöka hur fäder som sitter frihetsberövade upplever sitt faderskap. För att förstå detta har vi använt oss av fyra frågeställningar. 1. Hur beskriver männen faderskap och hur upplever de sitt eget faderskap? 2. Vilka känslor, kring faderskapet och kontakten med barnen under anstaltsvistelsen, beskrivs? 3. Vilka strategier använder fäderna för att hantera känslor som är relaterade till barnet? 4. Vilka möjligheter anser fäderna att sig ha att utöva föräldraskap under tid på anstalt? Denna uppsats är skriven ur fädernas perspektiv och inte barnens. Efter att genomfört åtta halvstrukturerade intervjuer på en anstalt, analyserade vi vårt resultat med hjälp av teorierna; coping, KASAM, socialkonstruktivistiskt perspektiv på faderskap och teorier som förklarar reaktioner i samband med skam. När vi sammanställde vårt resultat kunde vi se en tydlig bild av moderna fäder som önskade att få närvara mer i sina barns vardag. De berättade alla vilka svårigheter som fanns att under anstaltstid kunna utöva ett önskvärt faderskap. Orsakerna var flera; både dåliga besöks rum, som gjorde att man undvek att ta emot barnen på besök eller att man kunde vara placerad långt ifrån sin familj. Männen hanterade sina känslor och situationer på olika sätt, men de flesta använde undvikande copingstrategier. Vi tyckte oss även kunna utläsa ett uttryck för skamkänslor hos ett par av respondenterna. Kriminalvården insatser för fäder under anstalts tid skulle kunna utvecklas betydligt. Utbildning om barns behov borde vara obligatoriskt för all personal som arbetar inom kriminalvården. Besöksrum och besökslägenheter borde anpassas efter barns behov. Kriminalvården borde uttalat arbeta mer nätverksinriktat än vad de gör idag. Vår tolkning är att mycket av arbetet med familje- och barnperspektivet fått stå tillbaka och inte utvecklats i större utsträckning sedan kriminalvården 2006 infört ett utökat säkerhetsarbete. Fäderna i studien upplever att det förhöjda säkerhetsarbetet skapat svårigheter för dem att utöva sitt faderskap

PAPPA PÅ ANSTALT– En kvalitativ studie med åtta fäder på anstalt, om deras tankar och upplevelser kring sina barn

Uppsatsens syfte är att undersöka hur fäder som sitter frihetsberövade upplever sitt faderskap. För att förstå detta har vi använt oss av fyra frågeställningar. 1. Hur beskriver männen faderskap och hur upplever de sitt eget faderskap? 2. Vilka känslor, kring faderskapet och kontakten med barnen under anstaltsvistelsen, beskrivs? 3. Vilka strategier använder fäderna för att hantera känslor som är relaterade till barnet? 4. Vilka möjligheter anser fäderna att sig ha att utöva föräldraskap under tid på anstalt? Denna uppsats är skriven ur fädernas perspektiv och inte barnens. Efter att genomfört åtta halvstrukturerade intervjuer på en anstalt, analyserade vi vårt resultat med hjälp av teorierna; coping, KASAM, socialkonstruktivistiskt perspektiv på faderskap och teorier som förklarar reaktioner i samband med skam. När vi sammanställde vårt resultat kunde vi se en tydlig bild av moderna fäder som önskade att få närvara mer i sina barns vardag. De berättade alla vilka svårigheter som fanns att under anstaltstid kunna utöva ett önskvärt faderskap. Orsakerna var flera; både dåliga besöks rum, som gjorde att man undvek att ta emot barnen på besök eller att man kunde vara placerad långt ifrån sin familj. Männen hanterade sina känslor och situationer på olika sätt, men de flesta använde undvikande copingstrategier. Vi tyckte oss även kunna utläsa ett uttryck för skamkänslor hos ett par av respondenterna. Kriminalvården insatser för fäder under anstalts tid skulle kunna utvecklas betydligt. Utbildning om barns behov borde vara obligatoriskt för all personal som arbetar inom kriminalvården. Besöksrum och besökslägenheter borde anpassas efter barns behov. Kriminalvården borde uttalat arbeta mer nätverksinriktat än vad de gör idag. Vår tolkning är att mycket av arbetet med familje- och barnperspektivet fått stå tillbaka och inte utvecklats i större utsträckning sedan kriminalvården 2006 infört ett utökat säkerhetsarbete. Fäderna i studien upplever att det förhöjda säkerhetsarbetet skapat svårigheter för dem att utöva sitt faderskap

The dancer : Physical effort, muscle fibre types, and energy intake and expenditure

The Dancer Physical Effort, Muscle Fibre Types, and Energy Intake and Expenditure Monica Dahlström From Karolinska Institutet, Department of Medical Laboratory Sciences and Technology, Division of Clinical Physiology, Huddinge University Hospital, Huddinge, Sweden. The aims of this thesis were: -to estimate aerobic fitness in dancers and analyse possible changes during a three-year dance course and after a detraining period. -to compare different dance styles with regard to the duration of single exercises and the following rest periods. -to estimate the physical effort in dancers during training sessions in different styles of dance. -to compare the physical effort during training sessions in dance teachers with that of dance students. -to illuminate whether a deviating muscle fibre type distribution, if any, were training-induced or the result of selection of individuals with suitable fibre characteristics, muscle fibre type distribution was compared between children, at the very beginning of their professional dance training and dancers, who had performed professional dance training for 10 years. Moreover, muscle fibre type composition was analysed in dancers after detraining. -to investigate the dietary habits of female dancers and to compare the estimated daily energy intake (Ein) with the estimated daily energy expenditure (Eexp) and to explore whether a discrepancy found in female dance students between estimated daily Ein and estimated daily Eexp could be explained by a depressed basal energy expenditure (BMR). Results and conclusions: The estimated maximal oxygen uptake (VO2max) in the dance teachers and the dance students was 20-30% higher than in a randomly selected population with average physical activity. This and the 20% increase of estimated VO2max in the students over the three-year dance course indicate that dance training implies rather high demands on the cardiovascular system. Dance training is a predominantly intermittent type of exercise of brief active and rest periods. This concerns classical ballet as well as other dances styles as modern dance, jazz dance and character dance. The physical effort expressed as heart rate (HR) in % of maximal HR was approximately 70% for both teachers and students with no difference between the dance styles. This would correspond to a perceived exertion of "somewhat hard" to "hard" The blood lactate concentration indicates a moderate activation of the anaerobic energy production during dance training. Muscle fibre type composition in young dancers, even at the very beginning of their professional dance training, differs from that in the average individual and is characterised by a high % of type I fibres, similar to that found in 20 years old dancers. This, together with the fact that detraining did not change the muscle fibre type composition, supports the idea that the high percentage of type I fibres in dancers is due to a selection of individuals with suitable muscle fibre composition to the dance profession rather than being an effect of training. The 20% higher estimated daily Eexp than daily Ein as found in the dance students and no change in body weight over a six month period suggest that the Eexp was overestimated or the Ein was underestimated. In our estimation of daily Eexp a normal BMR was assumed. If the BMR had been lower than expected this would have led to an overestimation of the daily Eexp. In a subsequent study a normal BMR was demonstrated in the dance students. Thus, no support was found for a depressed BMR in the dancers, which consequently cannot contribute to explain the apparent discrepancy between daily Eexp and daily Ein. This may underline the uncertainty of dietary surveys, when applied to groups engaged in extreme physical activity as also pointed out by others. Key words: Children, dance, diet, exercise, exertion, female, fitness, muscle. ISBN 91-628-2205-

La Biennale di Venezia 49 : Esposizione Internazionale d’Arte

This two volume catalogue for the 49th Venice Biennale, the major theme of which is represented by the phrase “Plateau of Humankind,” features the work of artists from 64 countries and texts by more than 175 authors. The first volume includes a curatorial essay by Szeemann, and documentation of selected works. The second volume focuses on the work of artists who were chosen to represent the countries participating in the biennial. List of works. List of illustrations. Bio-bibliography 159 p. 19 bibl. ref

Proceedings of the fourth Resilience Engineering Symposium

These proceedings document the various presentations at the Fourth Resilience Engineering Symposium held on June 8-10, 2011, in Sophia-Antipolis, France. The Symposium gathered participants from five continents and provided them with a forum to exchange experiences and problems, and to learn about Resilience Engineering from the latest scientific achievements to recent practical applications. The First Resilience Engineering Symposium was held in Söderköping, Sweden, on October 25-29 2004. The Second Resilience Engineering Symposium was held in Juan-les-Pins, France, on November 8-10 2006, The Third Resilience Engineering Symposium was held in Juan-les-Pins, France, on October 28-30 2008. Since the first Symposium, resilience engineering has fast become recognised as a valuable complement to the established approaches to safety. Both industry and academia have recognised that resilience engineering offers valuable conceptual and practical basis that can be used to attack the problems of interconnectedness and intractability of complex socio-technical systems. The concepts and principles of resilience engineering have been tested and refined by applications in such fields as air traffic management, offshore production, patient safety, and commercial fishing. Continued work has also made it clear that resilience is neither limited to handling threats and disturbances, nor confined to situations where something can go wrong. Today, resilience is understood as the intrinsic ability of a system to adjust its functioning prior to, during, or following changes and disturbances, so that it can sustain required operations under both expected and unexpected conditions. This definition emphasizes the ability to continue functioning, rather than simply to react and recover from disturbances and the ability to deal with diverse conditions of functioning, expected as well as unexpected. For anyone who is interested in learning more about Resilience Engineering, the books published in the Ashgate Studies in Resilience Engineering provide an excellent starting point. Another sign that Resilience Engineering is coming of age is the establishment of the Resilience Engineering Association. The goal of this association is to provide a forum for coordination and exchange of experiences, by bringing together researchers and professionals working in the Resilience Engineering domain and organisations applying or willing to apply Resilience Engineering principles in their operations. The Resilience Engineering Association held its first General Assembly during the Fourth Symposium, and will in the future play an active role in the organisation of symposia and other activities related to Resilience Engineering