Formation of the Scandinavian Obesity Surgery Registry, SOReg.

Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism

Diversity of larger consumers enhances interference competition effects on smaller competitors

Competition between large and small species for the same food is common in a number of ecosystems including aquatic ones. How diversity of larger consumers affects the access of smaller competitors to a limiting resource is not well understood. We tested experimentally how species richness (0–3 spp.) of benthic deposit-feeding macrofauna changes meiofaunal ostracods’ incorporation of fresh organic matter from a stable-isotope-labeled cyanobacterial bloom, using fauna from the species-poor Baltic Sea. Presence of macrofauna mostly decreased meiofaunal incorporation of bloom material, depending on the macrofauna species present. As expected, the species identity of macrofauna influenced the incorporation of organic matter by meiofauna. Interestingly, our results show that, in addition, species richness of the macrofauna significantly reduced meiofauna incorporation of freshly settled nitrogen and carbon. With more than one macrofauna species, the reduction was always greater than expected from the single-species treatments. Field data from the Baltic Sea showed a negative correlation between macrofauna diversity and meiofaunal ostracod abundance, as expected from the experimental results. We argue that this is caused by interference competition, due to spatial niche differentiation between macrofauna species reducing the sediment volume in which ostracods can feed undisturbed by larger competitors. Interference from macrofauna significantly reduces organic matter incorporation by meiofauna, indicating that diversity of larger consumers is an important factor controlling the access of smaller competitors to a limiting food resource

Detailed Spatially Distributed Geothermal Heat-flow Data for Modeling of Basal Temperatures and Meltwater Production Beneath the Fennoscandian Ice Sheet

Accurate modeling of ice sheets requires proper information on boundary conditions, including the geothermal heat flow (or heat-flow density (HFD)). Traditionally, one uniform HFD value is adopted for the entire modeled domain. We have calculated a distributed, high-resolution HFD dataset for an approximate core area (Sweden and Finland) of the Scandinavian ice sheet, and imbedded this within lower-resolution data published for surrounding regions. Within the Last Glacial Maximum ice margin, HFD varies with a factor of as much as 2.8 (HFD values ranging between 30 and 83mWm–2), with an average of 49mWm–2. This average value is 17% higher than 42mWm–2, a common uniform value used in ice-sheet modeling studies of Fennoscandia. Using this new distributed dataset on HFD, instead of a traditional uniform value of 42mWm–2, yields a 1.4 times larger total basal meltwater production for the last glacial cycle. Furthermore, using the new dataset in high-resolution modeling results in increased spatial thermal gradients at the bed. This enhances and introduces new local and regional effects on basal ice temperatures and melt rates. We observed significant strengthening of local ‘ice streaming’, which in one case correlates to an ice-flow event previously interpreted from geomorphology. Regional to local variations in geothermal heat flow need to be considered for proper identification and treatment of thermal and hydraulic bed conditions, most likely also when studying Laurentide, Greenland and Antarctic ice sheets

Laboratory captivity can affect scores of metabolic rates and activity in wild brown trout

Phenotypic scoring of wild animals under standardized laboratory conditions is important as it allows field ecologists and evolutionary biologists to understand the development and maintenance of interindividual differences in plastic traits (e.g. behaviour and physiology). However, captivity is associated with a shift from a natural familiar environment to an unfamiliar and artificial environment, which may affect estimates of plastic phenotypic traits. In this study, we tested how previous experience with laboratory environments and time spent in captivity affects behavioural (i.e. activity) and metabolic (i.e. standard and maximum metabolic rates) scoring of our model species, wild brown trout Salmo trutta. We found that individuals with previous experience of laboratory captivity (10.5 months earlier) showed higher activity in an open field test than individuals with no prior experience of laboratory captivity. Previous experience with captivity had no significant effect on metabolic rates. However, metabolic rates seemed to increase with increasing time spent in captivity prior to the collection of measurements. Although there are benefits of keeping wild animals in captivity prior to scoring, our results suggest that while allowing for sufficient acclimatization researchers should aim at minimizing time in captivity of wild animals to increase accuracy and ecological relevance of the scoring of plastic phenotypic traits

Retained NK cell phenotype and functionality in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage non-alcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease. Here, we explored the presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD. Using 18-color-flow cytometry, substantial changes were observed in certain myeloid populations in patients as compared to controls. NK cell numbers, on the other hand, were not altered. Furthermore, only minor differences in expression of activating and inhibitory NK cell receptors were noted, with the exception of an increased expression of NKG2D on NK cells from patients with NASH. NK cell differentiation remained constant, and NK cells from these patients retain their ability to respond adequately upon stimulation. Instead, considerable alterations were observed between liver, adipose tissue, and peripheral blood NK cells, independently of disease status. Taken together, these results increase our understanding of the importance of the local microenvironment in shaping the NK cell compartment and stress the need for further studies exploring how NASH affects intrahepatic NK cells in humans.publishedVersio

Mother–infant interaction in schizophrenia:Transmitting risk or resilience? A systematic review of the literature

Purpose: The parent–infant relationship is an important context for identifying very early risk and resilience factors and targets for the development of preventative interventions. The aim of this study was to systematically review studies investigating the early caregiver–infant relationship and attachment in offspring of parents with schizophrenia. Methods: We searched computerized databases for relevant articles investigating the relationship between early caregiver–infant relationship and outcomes for offspring of a caregiver with a diagnosis of schizophrenia. Studies were assessed for risk of bias. Results: We identified 27 studies derived from 10 cohorts, comprising 208 women diagnosed with schizophrenia, 71 with other psychoses, 203 women with depression, 59 women with mania/bipolar disorder, 40 with personality disorder, 8 with unspecified mental disorders and 119 non-psychiatric controls. There was some evidence to support disturbances in maternal behaviour amongst those with a diagnosis of schizophrenia and there was more limited evidence of disturbances in infant behaviour and mutuality of interaction. Conclusions: Further research should investigate both sources of resilience and risk in the development of offspring of parents with a diagnosis of schizophrenia and psychosis. Given the lack of specificity observed in this review, these studies should also include maternal affective disorders including depressive and bipolar disorders

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT–PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A–D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2

Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

$\textbf{BACKGROUND}$: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. $\textbf{METHODS AND FINDINGS}$: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. $\textbf{CONCLUSIONS}$: Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.MRC Epidemiology Unit, Fenland study, EPIC-InterAct study, EPIC-Norfolk case-cohort study funding: this study was funded by the United Kingdom’s Medical Research Council through grants MC_UU_12015/1, MC_UU_12015/5, MC_PC_13046, MC_PC_13048 and MR/L00002/1. We acknowledge support from the National Institute for Health Research Biomedical Research Centre. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. EPIC-InterAct Study funding: funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). MRC Human Nutrition Research funding: This research was supported by the Medical Research Council (MC_UP_A090_1006) and Cambridge Lipidomics Biomarker Research Initiative (G0800783). The SABRE study was funded at baseline by the UK Medical Research Council, Diabetes UK and the British Heart Foundation and at follow-up by a programme grant from the Wellcome Trust (WT082464) and British Heart Foundation (SP/07/001/23603); Diabetes UK funded the metabolomics analyses (13/0004774). RJOS, EN, JRZ and AK received funding from the Swedish Research Council, Stockholm County Council, Novo Nordisk Foundation and Diabetes Wellness. DBS is supported by the Wellcome Trust grant number 107064. MIM is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. IB is supported by the Wellcome Trust grant WT098051