HIV infection significantly reduces lipoprotein lipase which remains low after 6 months of antiretroviral therapy

Purpose of the study Fractional clearance rate of apolipoprotein B100-containing lipoproteins is reduced in HIV infection before and after antiretroviral (ARV) treatment [1]. We compared lipoprotein lipase (LPL) activity and gene expression in HIV-positive subjects before and 6 months after ARV with HIV-negative controls. Methods Fasting blood post heparin total and hepatic lipase activity,adiponectin, leptin, insulin, glucose, and lipid measurementswere made in 32 HIV-infected and 15 HIVnegative controls. LPL was estimated by subtractinghepatic lipase from total lipase. Adiponectin, LPL andhormone sensitive lipase (HSL) gene expression weremeasured from iliac crest subcutaneous fat biopsies.Patients were tested before, and 6 months after randomisation to AZT/3TC (n = 15) or TDF/FTC (n = 17) with EFV.Between-group comparison was by Mann-Whitney andpaired samples by the Wilcoxon signed rank tests. Summary of results There were no differences in gender, ethnicity, baseline BMI, regional fat distribution (whole body DEXA) and visceral (VAT) and subcutaneous fat (SAT) measured by abdominal CT scans between controls and patients. Trunk fat/BMI ratio, VAT and VAT:SAT ratio significantly increased after 6-month ARV therapy (p = 0.01). There were no differences between groups in serum NEFA,HOMA and leptin levels. Selected other results are shown in Table 1. Conclusion Post heparin lipoprotein lipase activity is reduced in HIV and does not return to control levels after 6 months of ARV therapy. AZT-containing regimens are associated with a greater increase in LPL, LPL gene expression and plasma adiponectin than TDF

Clinical Outcomes Associated With Melanocytic Lesions Assessed Via Ancillary Gene Expression Profiling (GEP)

Aims/Objectives: Compare GEP assay prediction of 434 melanocytic lesions with dermatopathologist interpretation. Methods: Sensitivity and specificity of assay were calculated based on disagreement of assay prediction with dermatopathologist interpretation. Histologic features were recorded in disagreeing cases. Results: Eighty-five percent of lesions (369/434) had sufficient RNA for scoring. 74.2% 274/369 lesions were classified as “benign”, 11.9% (44/369) “indeterminate”, and 13.8% (51/369) “malignant”. 38/51 of lesions rendered “malignant” by dermatopathologists were classified “malignant” by assay (sensitivity = 74.5%). Lesions rendered by assay as “benign” but “malignant” by dermatopathologists were more likely to have rarer cytologic features. (13/51) lesions rendered “malignant” by dermatopathologists were classified by assay as “benign,” (4/13) or “indeterminate” (9/13). 270/318 lesions rendered “benign” by dermatopathologists were “benign” by assay (specificity = 84.9%). Of 44/369 “indeterminate” lesions, dermatopathologists rendered 9/44

Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality

Abstract: Background: Large changes in health behaviors achieved through intensive lifestyle intervention programs improve cardiovascular disease (CVD) risk factors among adults with type 2 diabetes. However, such interventions are not widely available, and there is limited evidence as to whether changes in behaviors affect risk of CVD events. Methods: Among 852 adults with screen-detected type 2 diabetes in the ADDITION-Cambridge study, we assessed changes in diet, physical activity, and alcohol use in the year following diabetes diagnosis. Participants were recruited from 49 general practices in Eastern England from 2002 to 2006, and were followed through 2014 for incidence of CVD events (n = 116) and all-cause mortality (n = 127). We used Cox proportional hazards regression to estimate hazard ratios (HR) for the associations of changes in behaviors with CVD and all-cause mortality. We estimated associations with CVD risk factors using linear regression. We considered changes in individual behaviors and overall number of healthy changes. Models adjusted for demographic factors, bodyweight, smoking, baseline value of the health behavior, and cardio-protective medication use. Results: Decreasing alcohol intake by ≥ 2 units/week was associated with lower hazard of CVD vs maintenance [HR: 0.56, 95% CI 0.36, 0.87]. Decreasing daily calorie intake by ≥ 300 kcal was associated with lower hazard of all-cause mortality vs maintenance [HR: 0.56, 95% CI 0.34, 0.92]. Achieving ≥ 2 healthy behavior changes was associated with lower hazard of CVD vs no healthy changes [HR: 0.39, 95% CI 0.18, 0.82]. Conclusions: In the year following diabetes diagnosis, small reductions in alcohol use were associated with lower hazard of CVD and small reductions in calorie intake were associated with lower hazard of all-cause mortality in a population-based sample. Where insufficient resources exist for specialist-led interventions, achievement of moderate behavior change targets is possible outside of treatment programs and may reduce long-term risk of CVD complications. Trial registration This trial is registered as ISRCTN86769081. Retrospectively registered 15 December 200

Moderate weight change following diabetes diagnosis and 10 year incidence of cardiovascular disease and mortality

AIMS/HYPOTHESIS: Adults with type 2 diabetes are at high risk of developing cardiovascular disease (CVD). Evidence of the impact of weight loss on incidence of CVD events among adults with diabetes is sparse and conflicting. We assessed weight change in the year following diabetes diagnosis and estimated associations with 10 year incidence of CVD events and all-cause mortality.METHODS: In a cohort analysis among 725 adults with screen-detected diabetes enrolled in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial, we estimated HRs for weight change in the year following diabetes diagnosis and 10 year incidence of CVD (n = 99) and all-cause mortality (n = 95) using Cox proportional hazards regression. We used linear regression to estimate associations between weight loss and CVD risk factors. Models were adjusted for age, sex, baseline BMI, smoking, occupational socioeconomic status, cardio-protective medication use and treatment group.RESULTS: Loss of ≥5% body weight in the year following diabetes diagnosis was associated with improvements in HbA1c and blood lipids and a lower hazard of CVD at 10 years compared with maintaining weight (HR 0.52 [95% CI 0.32, 0.86]). The associations between weight gain vs weight maintenance and CVD (HR 0.41 [95% CI 0.15, 1.11]) and mortality (HR 1.63 [95% CI 0.83, 3.19]) were less clear.CONCLUSIONS/INTERPRETATION: Among adults with screen-detected diabetes, loss of ≥5% body weight during the year after diagnosis was associated with a lower hazard of CVD events compared with maintaining weight. These results support the hypothesis that moderate weight loss may yield substantial long-term CVD reduction, and may be an achievable target outside of specialist-led behavioural treatment programmes.</p

Twisted supersymmetric 5D Yang-Mills theory and contact geometry

We extend the localization calculation of the 3D Chern-Simons partition function over Seifert manifolds to an analogous calculation in five dimensions. We construct a twisted version of N=1 supersymmetric Yang-Mills theory defined on a circle bundle over a four dimensional symplectic manifold. The notion of contact geometry plays a crucial role in the construction and we suggest a generalization of the instanton equations to five dimensional contact manifolds. Our main result is a calculation of the full perturbative partition function on a five sphere for the twisted supersymmetric Yang-Mills theory with different Chern-Simons couplings. The final answer is given in terms of a matrix model. Our construction admits generalizations to higher dimensional contact manifolds. This work is inspired by the work of Baulieu-Losev-Nekrasov from the mid 90's, and in a way it is covariantization of their ideas for a contact manifold.Comment: 28 pages; v2: minor mistake corrected; v3: matches published versio

Invariant Forms and Automorphisms of Locally Homogeneous Multisymplectic Manifolds

It is shown that the geometry of locally homogeneous multisymplectic manifolds (that is, smooth manifolds equipped with a closed nondegenerate form of degree > 1, which is locally homogeneous of degree k with respect to a local Euler field) is characterized by their automorphisms. Thus, locally homogeneous multisymplectic manifolds extend the family of classical geometries possessing a similar property: symplectic, volume and contact. The proof of the first result relies on the characterization of invariant differential forms with respect to the graded Lie algebra of infinitesimal automorphisms, and on the study of the local properties of Hamiltonian vector fields on locally multisymplectic manifolds. In particular it is proved that the group of multisymplectic diffeomorphisms acts (strongly locally) transitively on the manifold. It is also shown that the graded Lie algebra of infinitesimal automorphisms of a locally homogeneous multisymplectic manifold characterizes their multisymplectic diffeomorphisms.Comment: 25 p.; LaTeX file. The paper has been partially rewritten. Some terminology has been changed. The proof of some theorems and lemmas have been revised. The title and the abstract are slightly modified. An appendix is added. The bibliography is update

First and second variation formulae for the sub-Riemannian area in three-dimensional pseudo-hermitian manifolds

We calculate the first and the second variation formula for the sub-Riemannian area in three dimensional pseudo-hermitian manifolds. We consider general variations that can move the singular set of a C^2 surface and non-singular variation for C_H^2 surfaces. These formulas enable us to construct a stability operator for non-singular C^2 surfaces and another one for C2 (eventually singular) surfaces. Then we can obtain a necessary condition for the stability of a non-singular surface in a pseudo-hermitian 3-manifold in term of the pseudo-hermitian torsion and the Webster scalar curvature. Finally we classify complete stable surfaces in the roto-traslation group RT .Comment: 36 pages. Misprints corrected. Statement of Proposition 9.8 slightly changed and Remark 9.9 adde

Examination of the role of Mycoplasma bovis in bovine pneumonia and a mathematical model for its evaluation

The authors screened 34 large cattle herds for the presence of Mycoplasma bovis infection by examining slaughtered cattle for macroscopic lung lesions, by culturing M. bovis from lung lesions and at the same time by testing sera for the presence of antibodies against M. bovis. Among the 595 cattle examined, 33.9% had pneumonic lesions, mycoplasmas were isolated from 59.9% of pneumonic lung samples, and 10.9% of sera from those animals contained antibodies to M.bovis. In 25.2% of the cases M. bovis was isolated from lungs with no macroscopic lesions. The proportion of seropositive herds was 64.7%. The average seropositivity rate of individuals was 11.3% but in certain herds it exceeded 50%. A probability model was developed for examining the relationship among the occurrence of pneumonia, the isolation of M. bovis from the lungs and the presence of M. bovis specific antibodies in sera

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial

Introduction: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. Methods and analysis: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. Ethics and dissemination: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. Trial registration number: ISRCTN18399564

Geometric construction of D-branes in WZW models

The geometric description of D-branes in WZW models is pushed forward. Our starting point is a gluing condition\, $J_{+}=FJ_-$ that matches the model's chiral currents at the worldsheet boundary through a linear map $F$ acting on the WZW Lie algebra. The equivalence of boundary and gluing conditions of this type is studied in detail. The analysis involves a thorough discussion of Frobenius integrability, shows that $F$ must be an isometry, and applies to both metrically degenerate and nondegenerate D-branes. The isometry $F$ need not be a Lie algebra automorphism nor constantly defined over the brane. This approach, when applied to isometries of the form $F=R$ with $R$ a constant Lie algebra automorphism, validates metrically degenerate $R$-twined conjugacy classes as D-branes. It also shows that no D-branes exist in semisimple WZW models for constant\, $F=-R$.Comment: 23 pages, discussion of limitations of the gluing condition approach adde