Sexuality and Affection among Elderly German Men and Women in Long-Term Relationships: Results of a Prospective Population-Based Study

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was funded by the German Federal Ministry for Families, Senior Citizens, Women and Youth (AZ 314-1722-102/16; AZ 301-1720-295/2), the Ministry for Science, Research and Art Baden-Württemberg, and the University of Rostock (FORUN 989020; 889048)

Energy dependence of multiplicity fluctuations in heavy ion collisions

The energy dependence of multiplicity fluctuations was studied for the most central Pb+Pb collisions at 20A, 30A, 40A, 80A and 158A GeV by the NA49 experiment at the CERN SPS. The multiplicity distribution for negatively and positively charged hadrons is significantly narrower than Poisson one for all energies. No significant structure in energy dependence of the scaled variance of multiplicity fluctuations is observed. The measured scaled variance is lower than the one predicted by the grand-canonical formulation of the hadron-resonance gas model. The results for scaled variance are in approximate agreement with the string-hadronic model UrQMD

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

The Shapes of Cooperatively Rearranging Regions in Glass Forming Liquids

The shapes of cooperatively rearranging regions in glassy liquids change from being compact at low temperatures to fractal or ``stringy'' as the dynamical crossover temperature from activated to collisional transport is approached from below. We present a quantitative microscopic treatment of this change of morphology within the framework of the random first order transition theory of glasses. We predict a correlation of the ratio of the dynamical crossover temperature to the laboratory glass transition temperature, and the heat capacity discontinuity at the glass transition, Delta C_p. The predicted correlation agrees with experimental results for the 21 materials compiled by Novikov and Sokolov.Comment: 9 pages, 6 figure

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

Outcome reporting in randomised controlled trials and meta-analyses of appendicitis treatments in children: a systematic review

Background: Acute appendicitis is the most common surgical emergency in children. Despite this, there is no core outcome set (COS) described for randomised controlled trials (RCTs) in children with appendicitis and hence no consensus regarding outcome selection, definition and reporting. We aimed to identify outcomes currently reported in studies of paediatric appendicitis. / Methods: Using a defined, sensitive search strategy, we identified RCTs and systematic reviews (SRs) of treatment interventions in children with appendicitis. Included studies were all in English and investigated the effect of one or more treatment interventions in children with acute appendicitis or undergoing appendicectomy for presumed acute appendicitis. Studies were reviewed and data extracted by two reviewers. Primary (if defined) and all other outcomes were recorded and assigned to the core areas ‘Death’, ‘Pathophysiological Manifestations’, ‘Life Impact’, ‘Resource Use’ and ‘Adverse Events’, using OMERACT Filter 2.0. / Results: A total of 63 studies met the inclusion criteria reporting outcomes from 51 RCTs and nine SRs. Only 25 RCTs and four SRs defined a primary outcome. A total of 115 unique and different outcomes were identified. RCTs reported a median of nine outcomes each (range 1 to 14). The most frequently reported outcomes were wound infection (43 RCTs, nine SRs), intra-peritoneal abscess (41 RCTs, seven SRs) and length of stay (35 RCTs, six SRs) yet all three were reported in just 25 RCTs and five SRs. Common outcomes had multiple different definitions or were frequently not defined. Although outcomes were reported within all core areas, just one RCT and no SR reported outcomes for all core areas. Outcomes assigned to the ‘Death’ and ‘Life Impact’ core areas were reported least frequently (in six and 15 RCTs respectively). / Conclusions: There is a wide heterogeneity in the selection and definition of outcomes in paediatric appendicitis, and little overlap in outcomes used across studies. A paucity of studies report patient relevant outcomes within the ‘Life Impact’ core area. These factors preclude meaningful evidence synthesis, and pose challenges to designing prospective clinical trials and cohort studies. The development of a COS for paediatric appendicitis is warranted

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). 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 (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Introduction of a new model for time-continuous and non-contact investigations of in-vitro thrombolysis under physiological flow conditions

<p>Abstract</p> <p>Background</p> <p>Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model.</p> <p>Methods</p> <p>The model is based on a computer-controlled pump providing variable constant or pulsatile flows in a tube system filled with blood substitute. Clots can be fixed in a custom-built clot carrier within the tube system. The pressure decline at the clot carrier is measured as a novel way to measure lysis of the clot. With different experiments the hydrodynamic properties and reliability of the model were analyzed. Finally, the lysis rate of clots generated from human platelet rich plasma (PRP) was measured during a one hour combined application of diagnostic ultrasound (2 MHz, 0.179 W/cm²) and a thrombolytic agent (rt-PA) as it is commonly used for clinical sonothrombolysis treatments.</p> <p>Results</p> <p>All hydrodynamic parameters can be adjusted and measured with high accuracy. First experiments with sonothrombolysis demonstrated the feasibility of the model despite low lysis rates.</p> <p>Conclusions</p> <p>The model allows to adjust accurately all hydrodynamic parameters affecting thrombolysis under physiological flow conditions and for non-contact, time-continuous measurements. Low lysis rates of first sonothrombolysis experiments are primarily attributable to the high stability of the used PRP-clots.</p

Can we monitor heart attack in the troponin era: evidence from a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Troponins (highly sensitive biomarkers of myocardial damage) increase counts of myocardial infarction (MI) in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain.</p> <p>Methods</p> <p>Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC) in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria) using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA) or traditional biomarkers only (MI-AHAck).</p> <p>Results</p> <p>Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHA_ckdeclined by 18%.</p> <p>Conclusions</p> <p>Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHA_ckare consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.</p