Barriers to apply cardiovascular prediction rules in primary care: a postal survey

BACKGROUND: Although cardiovascular prediction rules are recommended by guidelines to evaluate global cardiovascular risk for primary prevention, they are rarely used in primary care. Little is known about barriers for application. The objective of this study was to evaluate barriers impeding the application of cardiovascular prediction rules in primary prevention. METHODS: We performed a postal survey among general physicians in two Swiss Cantons by a purpose designed questionnaire. RESULTS: 356 of 772 dispatched questionnaires were returned (response rate 49.3%). About three quarters (74%) of general physicians rarely or never use cardiovascular prediction rules. Most often stated barriers to apply prediction rules among rarely- or never-users are doubts concerning over-simplification of risk assessment using these instruments (58%) and potential risk of (medical) over-treatment (54%). 57% report that the numerical information resulting from prediction rules is often not helpful for decision-making in practice. CONCLUSION: If regular application of cardiovascular prediction rules in primary care is in demand additional interventions are needed to increase acceptance of these tools for patient management among general physicians

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19–21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work

An adverse outcome pathway for Parkinsonian motor deficits associated with mitochondrial complex I inhibition

Epidemiological studies have observed an association between pesticide exposure and the development of Parkinson\u2019s disease, but have not established causality. The concept of an adverse outcome pathway (AOP) has been developed as a framework for the organization of available information linking the modulation of a molecular target [molecular initiating event (MIE)], via a sequence of essential biological key events (KEs), with an adverse outcome (AO). Here, we present an AOP covering the toxicological pathways that link the binding of an inhibitor to mitochondrial complex I (i.e., the MIE) with the onset of parkinsonian motor de cits (i.e., the AO). This AOP was developed according to the Organisation for Economic Co-operation and Development guidelines and uploaded to the AOP database. The KEs linking complex I inhibition to parkinsonian motor de cits are mitochondrial dysfunction, impaired proteostasis, neuroin ammation, and the degeneration of dopaminergic neurons of the substantia nigra. These KEs, by convention, were linearly organized. However, there was also evidence of additional feed-forward connections and shortcuts between the KEs, possibly depending on the intensity of the insult and the model system applied. The present AOP demonstrates mechanistic plausibility for epidemiological observations on a relationship between pesticide exposure and an elevated risk for Parkinson\u2019s disease development

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

Characterization of the K2-38 planetary system: Unraveling one of the densest planets known to date

.-- Toledo-Padrón, B. et al.Context. An accurate characterization of the known exoplanet population is key to understanding the origin and evolution of planetary systems. Determining true planetary masses through the radial velocity (RV) method is expected to experience a great improvement thanks to the availability of ultra-stable echelle spectrographs. Aims. We took advantage of the extreme precision of the new-generation echelle spectrograph ESPRESSO to characterize the transiting planetary system orbiting the G2V star K2-38 located at 194 pc from the Sun with V 11.4. This system is particularly interesting because it could contain the densest planet detected to date. Methods. We carried out a photometric analysis of the available K2 photometric light curve of this star to measure the radius of its two known planets, K2-38b and K2-38c, with Pb = 4.01593 ± 0.00050 d and Pc = 10.56103 ± 0.00090 d, respectively. Using 43 ESPRESSO high-precision RV measurements taken over the course of 8 months along with the 14 previously published HIRES RV measurements, we modeled the orbits of the two planets through a Markov chain Monte Carlo analysis, significantly improving their mass measurements. Results. Using ESPRESSO spectra, we derived the stellar parameters, Teff = 5731 ± 66, log g = 4.38 ± 0.11 dex, and [Fe/H] = 0.26 ± 0.05 dex, and thus the mass and radius of K2-38, Ma = 1.03-0.02+0.04 MaS and Ra = 1.06-0.06+0.09 RaS. We determine new values for the planetary properties of both planets. We characterize K2-38b as a super-Earth with RP = 1.54 ± 0.14 RaS and Mp = 7.3-1.0+1.1 MaS, and K2-38c as a sub-Neptune with RP = 2.29 ± 0.26 RaS and Mp = 8.3-1.3+1.3 MaS. Combining the radius and mass measurements, we derived a mean density of ρp = 11.0-2.8+4.1 g cm-3 for K2-38b and ρp = 3.8-1.1+1.8 g cm-3 for K2-38c, confirming K2-38b as one of the densest planets known to date. Conclusions. The best description for the composition of K2-38b comes from an iron-rich Mercury-like model, while K2-38c is better described by a rocky-model with H2 envelope. The maximum collision stripping boundary shows how giant impacts could be the cause for the high density of K2-38b. The irradiation received by each planet places them on opposite sides of the radius valley. We find evidence of a long-period signal in the RV time-series whose origin could be linked to a 0.25-3 MJ planet or stellar activity.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737

Search for scalar leptoquarks and T-odd quarks in the acoplanar jet topology using 2.5 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV

A search for new physics in the acoplanar jet topology has been performed in 2.5 fb-1 of data from ppbar collisions at sqrt(s)=1.96 TeV, recorded by the D0 detector at the Fermilab Tevatron Collider. The numbers of events with exactly two acoplanar jets and missing transverse energy are in good agreement with the standard model expectations. The result of this search has been used to set a lower mass limit of 205 GeV at the 95% C.L. on the mass of a scalar leptoquark when this particle decays exclusively into a quark and a neutrino. In the framework of the Little Higgs model with T-parity, limits have also been obtained on the T-odd quark mass as a function of the T-odd photon mass

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO