Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Srv Mediated Dispersal of Streptococcal Biofilms Through SpeB Is Observed in CovRS+ Strains

Group A Streptococcus (GAS) is a human specific pathogen capable of causing both mild infections and severe invasive disease. We and others have shown that GAS is able to form biofilms during infection. That is to say, they form a three-dimensional, surface attached structure consisting of bacteria and a multi-component extracellular matrix. The mechanisms involved in regulation and dispersal of these GAS structures are still unclear. Recently we have reported that in the absence of the transcriptional regulator Srv in the MGAS5005 background, the cysteine protease SpeB is constitutively produced, leading to increased tissue damage and decreased biofilm formation during a subcutaneous infection in a mouse model. This was interesting because MGAS5005 has a naturally occurring mutation that inactivates the sensor kinase domain of the two component regulatory system CovRS. Others have previously shown that strains lacking covS are associated with decreased SpeB production due to CovR repression of speB expression. Thus, our results suggest the inactivation of srv can bypass CovR repression and lead to constitutive SpeB production. We hypothesized that Srv control of SpeB production may be a mechanism to regulate biofilm dispersal and provide a mechanism by which mild infection can transition to severe disease through biofilm dispersal. The question remained however, is this mechanism conserved among GAS strains or restricted to the unique genetic makeup of MGAS5005. Here we show that Srv mediated control of SpeB and biofilm dispersal is conserved in the invasive clinical isolates RGAS053 (serotype M1) and MGAS315 (serotype M3), both of which have covS intact. This work provides additional evidence that Srv regulated control of SpeB may mediate biofilm formation and dispersal in diverse strain backgrounds

Neutron Scattering Studies of spin excitations in hole-doped Ba0.67K0.33Fe2As2 superconductor

We report inelastic neutron scattering experiments on single crystals of superconducting Ba0.67K0.33Fe2As2 (Tc = 38 K). In addition to confirming the resonance previously found in powder samples, we find that spin excitations in the normal state form longitudinally elongated ellipses along the QAFM direction in momentum space, consistent with density functional theory predictions. On cooling below Tc, while the resonance preserves its momentum anisotropy as expected, spin excitations at energies below the resonance become essentially isotropic in the in-plane momentum space and dramatically increase their correlation length. These results suggest that the superconducting gap structures in Ba0.67Ka0.33Fe2As2 are more complicated than those suggested from angle resolved photoemission experiments

Equity in the use of antithrombotic drugs, beta-blockers and statins among Finnish coronary patients

Background Earlier studies have mainly reported the use of antithrombotic drugs, beta-blockers and statins among hospital patient populations or MI patients. This study aimed to describe the use of these drugs among middle-aged Finnish coronary patients and to identify patient groups in risk of being prescribed inadequate medication for secondary prevention of coronary heart disease. Methods One-year follow-up survey data from a random sample of a cohort of coronary patients were used along with register data linked to the survey. The response rate was 54% (n = 2650). The main outcome measures were use of antithrombotic drugs, beta-blockers and statins and the data were analysed using logistic regression analysis. Results Among men and women, respectively, 82% and 81% used beta-blockers, 95% and 89% used antithrombotic drugs, and 62% and 59% used statins. Younger men and men from higher socioeconomic groups were more likely to use statins, even after controlling for disease severity and comorbidity. In women, the age trend was reversed and no socioeconomic differences were found. Drug use increased with increased disease severity, but diabetes had only a slight effect. Conclusion The use of antithrombotic drugs and beta-blockers among Finnish coronary patients seemed to be rather appropriate and, to some extent, prescription practices of preventive medication varied according to patients' risk of coronary events. However, statin use was remarkably low among men with low socio-economic status, and there is need to improve preventive drug treatment among diabetic coronary patients.BioMed Central Open acces

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

How equitable are GP practice prescribing rates for statins?: an ecological study in four primary care trusts in North West England

BACKGROUND: There is a growing body of literature highlighting inequities in GP practice prescribing rates for a number of drug therapies. The small amount of research on statin prescribing has either focussed on variations rather than equity per se, been based on populations other than GP practices or has used cost-based prescribing rates. AIM: To explore the equity of GP practice prescribing rates for statins, using the theoretical framework of equity of treatment (also known as horizontal equity or comparative need). METHODS: The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates and health care needs indicators (HCNIs) were developed for all GP practices. RESULTS: Scatter-plots revealed large differences between individual GP practices, both within and between PCTs, in terms of the relationship between statin prescribing and healthcare need. In addition, there were large differences between GP practices in terms of the relationship between actual and expected prescribing rates for statins. Multiple regression analyses explained almost 30% of the variation in prescribing rates in the combined dataset, 25% in PCT1, 31% in PCT3, 51% in PC4 and 58% in PCT2. There were positive associations with variables relating to CHD hospital diagnoses and procedures and negative associations with variables relating to ethnicity, material deprivation, the proportion of patients aged over 75 years and single-handed GP practices. CONCLUSION: Overall, this study found inequitable relationships between actual and expected prescribing rates, and possible inequities in statin prescribing rates on the basis of ethnicity, deprivation, single-handed practices and the proportion of patients aged over 75 years

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Immune Response to Bifidobacterium bifidum Strains Support Treg/Th17 Plasticity

In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th) or regulatory (Treg) responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to further determine their capability to induce the differentiation of naïve CD4+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed