Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt

Changing indications and socio-demographic determinants of (adeno)tonsillectomy among children in England--are they linked? A retrospective analysis of hospital data.

OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent tonsillitis have influenced the socio-demographic profile of children who underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends study of Hospital Episodes Statistics data. We examined the age, sex and deprivation level, alongside OSAS diagnoses, among children aged <16 years who underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS: Among children aged <16 years, there were 29,697 and 27,732 (adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per 100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219) per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among children aged <4 years who underwent surgery increased from 18% to 39% between these study years and the proportion of children aged <4 years with OSAS from the most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS: (Adeno)tonsillectomy rates declined among children aged 4-15 years, which reflects national guidelines recommending the restriction of the operation to children with more severe recurrent throat infections. However, (adeno)tonsillectomy rates among pre-school children substantially increased over the past decade and one in five children undergoing the operation was aged <4 years in 2011/12.The increase in surgery rates in younger children is likely to have been driven by increased awareness and detection of OSAS, particularly among children from the most deprived areas

Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss: Links With Metabolic and Low-Grade Inflammation Markers

International audienceOBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at MO and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lacto-bacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at MO and throughout the follow-up after surgery independently of changes in food intake. CONCLUSIONS These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake. Diabetes 59:3049-3057, 201

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Caterpillars and fungal pathogens: two co-occurring parasites of an ant-plant mutualism

In mutualisms, each interacting species obtains resources from its partner that it would obtain less efficiently if alone, and so derives a net fitness benefit. In exchange for shelter (domatia) and food, mutualistic plant-ants protect their host myrmecophytes from herbivores, encroaching vines and fungal pathogens. Although selective filters enable myrmecophytes to host those ant species most favorable to their fitness, some insects can by-pass these filters, exploiting the rewards supplied whilst providing nothing in return. This is the case in French Guiana for Cecropia obtusa (Cecropiaceae) as Pseudocabima guianalis caterpillars (Lepidoptera, Pyralidae) can colonize saplings before the installation of their mutualistic Azteca ants. The caterpillars shelter in the domatia and feed on food bodies (FBs) whose production increases as a result. They delay colonization by ants by weaving a silk shield above the youngest trichilium, where the FBs are produced, blocking access to them. This probable temporal priority effect also allows female moths to lay new eggs on trees that already shelter caterpillars, and so to occupy the niche longer and exploit Cecropia resources before colonization by ants. However, once incipient ant colonies are able to develop, they prevent further colonization by the caterpillars. Although no higher herbivory rates were noted, these caterpillars are ineffective in protecting their host trees from a pathogenic fungus, Fusarium moniliforme (Deuteromycetes), that develops on the trichilium in the absence of mutualistic ants. Therefore, the Cecropia treelets can be parasitized by two often overlooked species: the caterpillars that shelter in the domatia and feed on FBs, delaying colonization by mutualistic ants, and the fungal pathogen that develops on old trichilia. The cost of greater FB production plus the presence of the pathogenic fungus likely affect tree growth

Perinatal mental ill health - the experiences of women from ethnic minority groups

This study aimed to investigate ethnic minority women’s experiences and opinions of perinatal mental health problems and the provision of perinatal mental health support services. An exploratory survey was undertaken using a questionnaire. Quantitative data were analysed using descriptive statistics and a simple thematic analysis was used for the qualitative data. A total of 51 responses from women of 14 different ethnic minority backgrounds were analysed. Women from minority ethnic groups face barriers to seeking help for perinatal mental ill health as a result of ongoing stigma and the poor attitudes and behaviours of health professionals and inappropriately designed services. Future interventions should focus on providing adequate cultural competency for health care professionals and ensure that all women are able to access culturally appropriate spaces to talk and be listened to within community settings and wider services

Determinants of the exclusive breastfeeding abandonment: psychosocial factors

OBJECTIVE To assess the determinants of exclusive breastfeeding abandonment. METHODS Longitudinal study based on a birth cohort in Viçosa, MG, Southeastern Brazil. In 2011/2012, 168 new mothers accessing the public health network were followed. Three interviews, at 30, 60, and 120 days postpartum, with the new mothers were conducted. Exclusive breastfeeding abandonment was analyzed in the first, second, and fourth months after childbirth. The Edinburgh Postnatal Depression Scale was applied to identify depressive symptoms in the first and second meetings, with a score of ≥ 12 considered as the cutoff point. Socioeconomic, demographic, and obstetric variables were investigated, along with emotional conditions and the new mothers’ social network during pregnancy and the postpartum period. RESULTS The prevalence of exclusive breastfeeding abandonment at 30, 60, and 120 days postpartum was 53.6% (n = 90), 47.6% (n = 80), and 69.6% (n = 117), respectively, and its incidence in the fourth month compared with the first was 48.7%. Depressive symptoms and traumatic delivery were associated with exclusive breastfeeding abandonment in the second month after childbirth. In the fourth month, the following variables were significant: lower maternal education levels, lack of homeownership, returning to work, not receiving guidance on breastfeeding in the postpartum period, mother’s negative reaction to the news of pregnancy, and not receiving assistance from their partners for infant care. CONCLUSIONS Psychosocial and sociodemographic factors were strong predictors of early exclusive breastfeeding abandonment. Therefore, it is necessary to identify and provide early treatment to nursing mothers with depressive symptoms, decreasing the associated morbidity and promoting greater duration of exclusive breastfeeding. Support from health professionals, as well as that received at home and at work, can assist in this process

A pilot randomized controlled study of the mental health first aid elearning course with UK medical students

Background: Medical students face many barriers to seeking out professional help for their mental health, including stigma relating to mental illness, and often prefer to seek support and advice from fellow students. Improving medical students’ mental health literacy and abilities to support someone experiencing a mental health problem could reduce barriers to help seeking and improve mental health in this population. Mental Health First Aid (MHFA) is an evidence-based intervention designed to improve mental health literacy and ability to respond to someone with a mental health problem. This pilot randomised controlled trial aims to evaluate the MHFA eLearning course in UK medical students. Methods: Fifty-five medical students were randomised to receive six weeks access to the MHFA eLearning course (n = 27) or to a no-access control group (n = 28). Both groups completed baseline (pre-randomisation) and follow-up (six weeks post-randomisation) online questionnaires measuring recognition of a mental health problem, mental health first aid intentions, confidence to help a friend experiencing a mental health problem, and stigmatising attitudes. Course feedback was gathered at follow-up. Results: More participants were lost follow-up in the MHFA group (51.9%) compared to control (21.4%). Both intention-to-treat (ITT) and non-ITT analyses showed that the MHFA intervention improved mental health first aid intentions (p = <.001) and decreased stigmatising attitudes towards people with mental health problems (p = .04). While ITT analysis found no significant Group x Time interaction for confidence to help a friend, the non-ITT analysis did show the intervention improved confidence to help a friend with mental health problems (p =<.001), and improved mental health knowledge (p = .003). Medical students in the intervention group reported a greater number of actual mental health first aid actions at follow-up (p = .006). Feedback about the MHFA course was generally positive, with participants stating it helped improve their knowledge and confidence to help someone. Conclusion: This pilot study demonstrated the potential for the MHFA eLearning course to improve UK medical students’ mental health first aid skills, confidence to help a friend and stigmatising attitudes. It could be useful in supporting their own and others’ mental health while studying and in their future healthcare careers

Benchmarking Materials Property Prediction Methods: The Matbench Test Set and Automatminer Reference Algorithm

We present a benchmark test suite and an automated machine learning procedure for evaluating supervised machine learning (ML) models for predicting properties of inorganic bulk materials. The test suite, Matbench, is a set of 13 ML tasks that range in size from 312 to 132k samples and contain data from 10 density functional theory-derived and experimental sources. Tasks include predicting optical, thermal, electronic, thermodynamic, tensile, and elastic properties given a materials composition and/or crystal structure. The reference algorithm, Automatminer, is a highly-extensible, fully-automated ML pipeline for predicting materials properties from materials primitives (such as composition and crystal structure) without user intervention or hyperparameter tuning. We test Automatminer on the Matbench test suite and compare its predictive power with state-of-the-art crystal graph neural networks and a traditional descriptor-based Random Forest model. We find Automatminer achieves the best performance on 8 of 13 tasks in the benchmark. We also show our test suite is capable of exposing predictive advantages of each algorithm - namely, that crystal graph methods appear to outperform traditional machine learning methods given ~10^4 or greater data points. The pre-processed, ready-to-use Matbench tasks and the Automatminer source code are open source and available online (http://hackingmaterials.lbl.gov/automatminer/). We encourage evaluating new materials ML algorithms on the MatBench benchmark and comparing them against the latest version of Automatminer.Comment: Main text, supplemental inf

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration