Prediction and estimation of effective population size

Effective population size (Ne) is a key parameter in population genetics. It has important applications in evolutionary biology, conservation genetics, and plant and animal breeding, because it measures the rates of genetic drift and inbreeding and affects the efficacy of systematic evolutionary forces such as mutation, selection and migration. We review the developments in predictive equations and estimation methodologies of effective size. In the prediction part, we focus on the equations for populations with different modes of reproduction, for populations under selection for unlinked or linked loci, and for the specific applications to conservation genetics. In the estimation part, we focus on methods developed for estimating the current or recent effective size from molecular marker or sequence data. We discuss some underdeveloped areas in predicting and estimating Ne for future research

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

The CARMENES search for exoplanets around M dwarfs High-resolution optical and near-infrared spectroscopy of 324 survey stars

The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least R >80 000, and we measure its RV, Hα emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, Q, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s−1 in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s−1

The CARMENES search for exoplanets around M dwarfs. Two temperate Earth-mass planet candidates around Teegarden’s Star

Context.Teegarden’s Star is the brightest and one of the nearest ultra-cool dwarfs in the solar neighbourhood. For its late spectral type (M7.0 V),the star shows relatively little activity and is a prime target for near-infrared radial velocity surveys such as CARMENES.Aims.As part of the CARMENES search for exoplanets around M dwarfs, we obtained more than 200 radial-velocity measurements of Teegarden’sStar and analysed them for planetary signals.Methods.We find periodic variability in the radial velocities of Teegarden’s Star. We also studied photometric measurements to rule out stellarbrightness variations mimicking planetary signals.Results.We find evidence for two planet candidates, each with 1.1M⊕minimum mass, orbiting at periods of 4.91 and 11.4 d, respectively. Noevidence for planetary transits could be found in archival and follow-up photometry. Small photometric variability is suggestive of slow rotationand old age.Conclusions.The two planets are among the lowest-mass planets discovered so far, and they are the first Earth-mass planets around an ultra-cooldwarf for which the masses have been determined using radial velocities.We thank the referee Rodrigo Díaz for a careful review andhelpful comments. M.Z. acknowledges support from the Deutsche Forschungs-gemeinschaft under DFG RE 1664/12-1 and Research Unit FOR2544 “BluePlanets around Red Stars”, project no. RE 1664/14-1. CARMENES isan instrument for the Centro Astronómico Hispano-Alemán de Calar Alto(CAHA, Almería, Spain). CARMENES is funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de InvestigacionesCientíficas (CSIC), the European Union through FEDER/ERF FICTS-2011-02 funds, and the members of the CARMENES Consortium (Max-Planck-Institut für Astronomie, Instituto de Astrofísica de Andalucía, LandessternwarteKönigstuhl, Institut de Ciències de l’Espai, Institut für Astrophysik Göttingen,Universidad Complutense de Madrid, Thüringer Landessternwarte Tautenburg,Instituto de Astrofísica de Canarias, Hamburger Sternwarte, Centro de Astro-biología and Centro Astronómico Hispano-Alemán), with additional contribu-tions by the Spanish Ministry of Economy, the German Science Foundationthrough the Major Research Instrumentation Programme and DFG ResearchUnit FOR2544 “Blue Planets around Red Stars”, the Klaus Tschira Stiftung, thestates of Baden-Württemberg and Niedersachsen, and by the Junta de Andalucía.Based on data from the CARMENES data archive at CAB (INTA-CSIC). Thisarticle is based on observations made with the MuSCAT2 instrument, devel-oped by ABC, at Telescopio Carlos Sánchez operated on the island of Tener-ife by the IAC in the Spanish Observatorio del Teide. Data were partly col-lected with the 150-cm and 90-cm telescopes at the Sierra Nevada Observa-tory (SNO) operated by the Instituto de Astrofísica de Andalucía (IAA-CSIC).Data were partly obtained with the MONET/South telescope of the MOnitoringNEtwork of Telescopes, funded by the Alfried Krupp von Bohlen und HalbachFoundation, Essen, and operated by the Georg-August-Universität Göttingen,the McDonald Observatory of the University of Texas at Austin, and the SouthAfrican Astronomical Observatory. We acknowledge financial support from theSpanish Agencia Estatal de Investigación of the Ministerio de Ciencia, Inno-vación y Universidades and the European FEDER/ERF funds through projectsAYA2015-69350-C3-2-P, AYA2016-79425-C3-1/2/3-P, AYA2018-84089, BES-2017-080769, BES-2017-082610, ESP2015-65712-C5-5-R, ESP2016-80435-C2-1/2-R, ESP2017-87143-R, ESP2017-87676-2-2, ESP2017-87676-C5-1/2/5-R, FPU15/01476, RYC-2012-09913, the Centre of Excellence ”Severo Ochoa”and ”María de Maeztu” awards to the Instituto de Astrofísica de Canarias (SEV-2015-0548), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Cen-tro de Astrobiología (MDM-2017-0737), the Generalitat de Catalunya throughCERCA programme”, the Deutsches Zentrum für Luft- und Raumfahrt throughgrants 50OW0204 and 50OO1501, the European Research Council through grant694513, the Italian Ministero dell’instruzione, dell’università de della ricerca andUniversità degli Studi di Roma Tor Vergata through FFABR 2017 and “Mis-sion: Sustainability 2016”, the UK Science and Technology Facilities Council through grant ST/P000592/1, the Israel Science Foundation through grant848/16, the Chilean CONICYT-FONDECYT through grant 3180405, the Mexi-can CONACYT through grant CVU 448248, the JSPS KAKENHI through grantsJP18H01265 and 18H05439, and the JST PRESTO through grant JPMJPR1775

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

The CARMENES search for exoplanets around M dwarfs HD147379 b: A nearby Neptune in the temperate zone of an early-M dwarf

We report on the first star discovered to host a planet detected by radial velocity (RV) observations obtained within the CARMENES survey for exoplanets around M dwarfs. HD 147379 (V = 8.9 mag, M = 0.58 ± 0.08 M⊙), a bright M0.0 V star at a distance of 10.7 pc, is found to undergo periodic RV variations with a semi-amplitude of K = 5.1 ± 0.4 m s−1 and a period of P = 86.54 ± 0.06 d. The RV signal is found in our CARMENES data, which were taken between 2016 and 2017, and is supported by HIRES/Keck observations that were obtained since 2000. The RV variations are interpreted as resulting from a planet of minimum mass mP sin i = 25 ± 2 M⊕, 1.5 times the mass of Neptune, with an orbital semi-major axis a = 0.32 au and low eccentricity (e < 0.13). HD 147379 b is orbiting inside the temperate zone around the star, where water could exist in liquid form. The RV time-series and various spectroscopic indicators show additional hints of variations at an approximate period of 21.1 d (and its first harmonic), which we attribute to the rotation period of the star.FEDER/ERF FICTS-2011-02 fundsMajor Research Instrumentation Programme and DFG Research Unit FOR2544 “Blue Planets around Red StarsEuropean Research Council (ERC-279347), Deutsche Forschungsgemeinschaft (RE 1664/12-1, RE 2694/4-1), Bundesministerium für Bildung und Forschung (BMBF-05A14MG3, BMBF-05A17MG3), Spanish Ministry of Economy and Competitiveness (MINECO, grants AYA2015-68012-C2-2-P, AYA2016-79425-C3-1,2,3-P, AYA2015-69350-C3-2-P, AYA2014-54348-C03- 01, AYA2014-56359-P, AYA2014-54348-C3-2-R, AYA2016-79425-C3-3-P and 2013 Ramòn y Cajal program RYC-2013-14875), Fondo Europeo de Desarrollo Regional (FEDER, grant ESP2016-80435-C2-1-R, ESP2015-65712-C5- 5-R), Generalitat de Catalunya/CERCA programme, Spanish Ministerio de Educación, Cultura y Deporte, programa de Formación de Profesorado Universitario (grant FPU15/01476), Deutsches Zentrum für Luft- und Raumfahrt (grants 50OW0204 and 50OO1501), Office of Naval Research Global (award no. N62909-15-1-2011), Mexican CONACyT grant CB-2012-183007

Digestibilidade aparente de dietas práticas com diferentes relações energia:proteína em juvenis de pirarucu

The objective of this work was to determine the apparent digestibility of nutrients and energy of diets for pirarucu (Arapaima gigas) juveniles. Eight experimental diets containing four energy:protein ratios (11, 10.1, 9, 8 kcal digestible energy per gram of crude protein) and two non-protein energy sources (soybean oil and poultry fat) were tested in a 4x2 factorial scheme, in triplicates. Two hundred and forty pirarucu juveniles weighting 96.8±2.3 g were distributed in 24 cylindrical-conical fiberglass tanks, adapted for feces collection (modified Guelph system). Fish were fed twice a day to apparent satiation, with experimental diets containing 0.5% of chromium oxide as inert marker in order to determine the apparent digestibility coefficients. Diets containing an energy:protein ratio of 9 kcal digestible energy per gram of crude protein resulted in significantly lower apparent digestibility coefficient for dry matter, crude protein and non-nitrogenous extract. The highest apparent digestibility coefficients for crude fat was obtained with soybean oil. The dietary energy:protein ratio influences the nutrient and energy apparent digestibility coefficients to pirarucu juveniles

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.