The role of long-term mechanical circulatory support in patients with advanced heart failure

In patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be considered. LVADs can be implanted as a bridge to transplantation or as an alternative to heart transplantation: destination therapy. In the Netherlands, long-term LVAD therapy is gaining importance as a result of increased prevalence of heart failure together with a low number of heart transplantations due to shortage of donor hearts. As a result, the difference between bridge to transplantation and destination therapy is becoming more artificial since, at present, most patients initially implanted as bridge to transplantation end up receiving extended LVAD therapy. Following LVAD implantation, survival after 1, 2 and 3 years is 83%, 76% and 70%, respectively. Quality of life improves substantially despite important adverse events such as device-related infection, stroke, major bleeding and right heart failure. Early referral of potential candidates for long-term MCS is of utmost importance and positively influences outcome. In this review, an overview of the indications, contraindications, patient selection, clinical outcome and optimal time of referral for long-term MCS is given

Functional analysis of four LDLR 5'UTR and promoter variants in patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disease characterised by increased low-density lipoprotein cholesterol (LDL-C) levels. The functionality of four novel variants within the LDLR 5'UTR and promoter located at c.-13A>G, c.-101T>C, c.-121T>C and c.-215A>G was investigated using in silico and in vitro assays, and a systemic bioinformatics analysis of all 36 reported promoter variants are presented. Bioinformatic tools predicted that all four variants occurred in sites likely to bind transcription factors and that binding was altered by the variant allele. Luciferase assay was performed for all the variants. Compared with wild type, the c.-101T>C and c.-121T>C variants showed significantly lower mean (±SD) luciferase activity (64±8 and 72±8%, all PG or c.-215A>G variants (96±15 and 100±12%), suggesting these variants are not FH causing. Similar results were seen for the c.-101T>C and c.-121T>C variants in lipid-depleted serum. However, a significant reduction in luciferase activity was seen in the c.-215A>G variant in lipid-depleted serum. Electrophoretic-mobility shift assays identified allele-specific binding of liver (hepatoma) nuclear proteins to c.-121T>C and suggestive differential binding to c.-101T>C but no binding to c.-215A>G. These data highlight the importance of in vitro testing of reported LDLR promoter variants to establish their role in FH. The functional assays performed suggest that the c.-101T>C and c.-121T>C variants are pathogenic, whereas c.-13A>G variant is benign, and the status of c.-215A>G remains unclear.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.199

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Background: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). Methods and results: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (. P-value for heterogeneity=0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. Conclusions: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD

Measurements of Transverse Energy Flow in Deep-Inelastic Scattering at HERA

Measurements of transverse energy flow are presented for neutral current deep-inelastic scattering events produced in positron-proton collisions at HERA. The kinematic range covers squared momentum transfers Q^2 from 3.2 to 2,200 GeV^2, the Bjorken scaling variable x from 8.10^{-5} to 0.11 and the hadronic mass W from 66 to 233 GeV. The transverse energy flow is measured in the hadronic centre of mass frame and is studied as a function of Q^2, x, W and pseudorapidity. A comparison is made with QCD based models. The behaviour of the mean transverse energy in the central pseudorapidity region and an interval corresponding to the photon fragmentation region are analysed as a function of Q^2 and W.Comment: 26 pages, 8 figures, submitted to Eur. Phys.

FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.Most co-authors were financialy supported with their respective inistitution. Some of the co-authors were financialy supportrd by the Safe and Efficient Chemistry by Design (SafeChem) project (grant no. DIA 2018/11) funded by the Swedish Foundation for Strategic Environmental Research, and by the PARC project (grant no. 101057014) funded under the European Union's Horizon Europe Research and Innovation program

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4

Differential (2+1) Jet Event Rates and Determination of alpha_s in Deep Inelastic Scattering at HERA

Events with a (2+1) jet topology in deep-inelastic scattering at HERA are studied in the kinematic range 200 < Q^2< 10,000 GeV^2. The rate of (2+1) jet events has been determined with the modified JADE jet algorithm as a function of the jet resolution parameter and is compared with the predictions of Monte Carlo models. In addition, the event rate is corrected for both hadronization and detector effects and is compared with next-to-leading order QCD calculations. A value of the strong coupling constant of alpha_s(M_Z^2)= 0.118+- 0.002 (stat.)^(+0.007)_(-0.008) (syst.)^(+0.007)_(-0.006) (theory) is extracted. The systematic error includes uncertainties in the calorimeter energy calibration, in the description of the data by current Monte Carlo models, and in the knowledge of the parton densities. The theoretical error is dominated by the renormalization scale ambiguity.Comment: 25 pages, 6 figures, 3 tables, submitted to Eur. Phys.