Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPPIRI3L/iASPP

Background: Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls. Methods and Results: Studying one marker at a time, we found a region spanning the gene RAI ( alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age. In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3' d1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41 - 4.23, p = 0.0008, all cases; RR = 6.29 (1.49 - 26.6), p = 0.01, cases up to 55 years of age). Conclusion: We expect the marker RAI-3' d1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

Arcanobacterium phocae infection in mink (Neovison vison), seals (Phoca vitulina, Halichoerus grypus) and otters (Lutra lutra)

Abstract Background Infectious skin disorders are not uncommon in mink. Such disorders are important as they have a negative impact on animal health and welfare as well as on the quality and value of the fur. This study presents the isolation of Arcanobacterium phocae from mink with severe skin lesions and other pathological conditions, and from wild seals and otters. Results In 2015, A. phocae was isolated for the first time in Denmark from outbreaks of dermatitis in mink farms. The outbreaks affected at least 12 farms. Originating from these 12 farms, 23 animals cultured positive for A. phocae. The main clinical findings were necrotizing pododermatitis or dermatitis located to other body sites, such as the lumbar and cervical regions. A. phocae could be isolated from skin lesions and in nine animals also from liver, spleen and lung, indicating a systemic spread. The bacterium was also, for the first time in Denmark, detected in dead seals (n = 9) (lungs, throat or wounds) and otters (n = 2) (throat and foot). Conclusions An infectious skin disorder in mink associated with A. phocae has started to occur in Danish farmed mink. The origin of the infection has not been identified and it is still not clear what the pathogenesis or the port of entry for A. phocae infections are

The importance of adverse childhood experiences for labour market trajectories over the life course: a longitudinal study

Abstract Background Transitioning from school to work is important in influencing people’s trajectories throughout their life course. This study investigated the extent to which adverse childhood experiences (ACEs) were associated with differences in labour market trajectories for young adults in the context of a Nordic child care regime with low levels of child poverty. Methods Information on labour market participation, educational events, and public transfer records was recoded into seven state spaces for each month between ages 16 and 32 for a cohort of Danish adolescents born in a rural county in 1983 (N = 3373). Cluster analysis of the sequences using the optimal matching algorithm was used to identify groups with similar trajectories. Multinomial regression was used to assess the association between self-reported ACEs and cluster membership, taking gender and family of origin into account. Results ‘In employment’ was the state space in which the young adults spent the most time over their early life courses (mean: 85 out of 204 months; 42%). Cluster analysis identified three clusters. Cluster 3 was most distinct, where the mean time ‘outside the labour market’ was 149 months (73%), and only 17 months (8%) were spent ‘in employment’. Cumulative ACEs increased the probability of being included in Cluster 3 (OR: 1.51). Experiencing parental divorce (OR: 3.05), witnessing a violent event (OR: 3.70), and being abused (OR: 5.64) were most strongly associated with Cluster 3 membership. Conclusions Labour market trajectories among adolescents with a higher number of ACEs consisted of more time outside the labour market, compared to adolescents who had experienced fewer adversities. The lasting consequences of childhood adversity should be taken more into account in welfare policies, even in countries such as Denmark, with high social security levels and high-quality universal childcare

Characterisation of Gut Microbiota in Ossabaw and Göttingen Minipigs as Models of Obesity and Metabolic Syndrome

Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs' cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine.Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs

COPE-ICD: A randomised clinical trial studying the effects and meaning of a comprehensive rehabilitation programme for ICD recipients -design, intervention and population

<p>Abstract</p> <p>Background</p> <p>Growing evidence exists that living with an ICD can lead to fear and avoidance behaviour including the avoidance of physical activity. It has been suggested that psychological stress can increase the risk of shock and predict death. Small studies have indicated a beneficial effect arising from exercise training and psychological intervention, therefore a large-scale rehabilitation programme was set up.</p> <p>Methods/Design</p> <p>A mixed methods embedded experimental design was chosen to include both quantitative and qualitative measures. A randomised clinical trial is its primary component. 196 patients (power-calculated) were block randomised to either a control group or intervention group at a single centre. The intervention consists of a 1-year psycho-educational component provided by two nurses and a 12-week exercise training component provided by two physiotherapists. Our hypothesis is that the COPE-ICD programme will reduce avoidance behaviour, sexual dysfunction and increase quality of life, increase physical capability, reduce the number of treatment-demanding arrhythmias, reduce mortality and acute re-hospitalisation, reduce sickness leading to absence from work and be cost-effective. A blinded investigator will perform all physical tests and data collection.</p> <p>Discussion</p> <p>Most participants are men (79%) with a mean age of 58 (range 20-85). Most ICD implantations are on primary prophylactic indication (66%). 44% is NYHA II. Mean walk capacity (6MWT) is 417 m. Mean perception of General Health (SF-36) is PCS 42.6 and MCS 47.1.</p> <p>A large-scale ICD rehabilitation trial including psycho-educational intervention and exercise training has been initiated and will report findings starting in 2011.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00569478">NCT00569478</a></p

The combined effects of warming, ocean acidification, and fishing on the northeast Atlantic cod (Gadus morhua) in the Barents Sea

With a biomass of ∼4 million tonnes, and annual catches of 900 000 tonnes, the northeast Atlantic (NEA) cod stock in the Barents Sea is the world’s largest. Scientists have been trying to explain the variability in recruitment of this stock for over 100 years, in particular connecting it to spawning stock biomass and environmental factors such as temperature. It has been suggested that the combination of ocean acidification and global warming will lead to a significant decrease in the spawning stock biomass and an eventual (end of this century) collapse of the NEA cod stock in the Barents Sea. We show that a temperature- and OA-driven decline in recruits will likely lead to a smaller cod stock, but not to a collapse. Instead, the level of fishing pressure and, not least, the choice of the recruitment function applied in simulations and how it relates to temperature, is extremely important when making such forecasts. Applying a non-linear relationship between temperature and spawning stock biomass—as has been done in studies that predict a collapse of the NEA cod stock—does not improve accuracy and, in addition, adds a large decrease in number of recruits that is not biologically supported.publishedVersio

Substitution of meat and fish with vegetables or potatoes and risk of myocardial infarction

AbstractRed meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50–64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.</jats:p

Substitutions of red meat, poultry and fish and risk of myocardial infarction

AbstractRed meat has been suggested to be adversely associated with risk of myocardial infarction (MI), but previous studies have rarely taken replacement foods into consideration. We aimed to investigate optimal substitutions between and within the food groups of red meat, poultry and fish for MI prevention. We followed up 55 171 women and men aged 50–64 years with no known history of MI at recruitment. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for specified food substitutions of 150 g/week. During a median follow-up time of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for replacing red meat with fatty fish was 0·76 (95 % CI 0·64, 0·89), whereas the HR for replacing red meat with lean fish was 1·00 (95 % CI 0·89, 1·14). Similarly, replacing poultry with fatty but not lean fish was inversely associated with MI: the HR was 0·81 (95 % CI 0·67, 0·98) for fatty fish and was 1·08 (95 % CI 0·92, 1·27) for lean fish. The HR for replacing lean with fatty fish was 0·75 (95 % CI 0·60, 0·94). Replacing processed with unprocessed red meat was not associated with MI. Among men, a similar pattern was found, although the associations were not statistically significant. This study suggests that replacing red meat, poultry or lean fish with fatty fish is associated with a lower risk of MI.</jats:p