85 research outputs found

    The Eco-Efficiency Premium Puzzle

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    There exists a widespread consensus among mainstream academics and investors that socially responsible investing (SRI) leads to inferior, rather than superior, portfolio performance. Using Innovest’s well-established corporate ecoefficiency scores, we provide evidence to the contrary. We compose two equity portfolios that differ in eco-efficiency characteristics and find that our highranked portfolio provided substantially higher average returns compared to its low-ranked counterpart over the period 1995-2003. Using a wide range of performance attribution techniques to address common methodological concerns, we show that this performance differential cannot be explained by differences in market sensitivity, investment style, or industry-specific components. We finally investigate whether this eco-efficiency premium puzzle withstands the inclusion of transaction costs scenarios, and evaluate how excess returns can be earned in a practical setting via a best-in-class stock selection strategy. The results remain significant under all levels of transactions costs, thus suggesting that the incremental benefits of SRI can be substantial

    Association between HTR2C polymorphisms and weight loss in obese patients

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    OBJECTIVE To investigate whether the HTR2C rsUU334 and 759 C/T polymorphisms are associated with weight loss in an anti- obesity programme. DESIGN AND METHODS A longitudinal observational follow-up study was used to assess the association between HTR2C genotypes and weight loss during a nine month programme in an obesity clinic. Caucasian patients aged 18 years or older were included. Data were extracted from the patients' medical records. In total, 128 patients were included 129 males). RESULTS There was a significant association between the HTR2C 759 T allele and resistance to weight loss in the first month of the programme. For each T allele present, there was 0.78% (95% confidence interval [95%-CI] 0.19-1.38; P = 0.011 less weight loss (as a percentage of the body weight at start). Patients carrying the variant HTR2C 759 T allele were also less likely to reach > 7% weight loss (odds ratio [OR] 0.23; 95%-CI 0.06- 0,85; P = 0.028), and dropped out of the programme sooner [-0.78 months; 95%-CI -1.51- -0.06; P = 0.035; corrected for gender). No associations with the HTR2C rsUU334- genotype and any of the primary endpoints for weight loss or secondary endpoints were found. CONCLUSION Patients carrying the HTR2C 759 T allele were more resistant to weight loss and dropped out of the programme sooner. However, these effects were small and only explained a small part of a very complex puzzle. Genotyping HTR2C to predict a patient's chance of success in an obesity clinic is therefore not warranted

    Arterio-ureteral fistula:a nationwide cross-sectional questionnaire analysis

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    PURPOSE: Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but potentially lethal. Although the number of reports has increased over the past two decades, the true incidence and contemporary urologists’ experience and approach in clinical practice remains unknown. This research is conducted to provide insight in the incidence of AUF in The Netherlands, and the applied diagnostic tests and therapeutic approaches in modern practice. METHODS: A nationwide cross-sectional questionnaire analysis was performed by sending a survey to all registered Dutch urologists. Data collection included information on experience with patients with AUF; and their medical history, diagnostics, treatment, and follow-up, and were captured in a standardized template by two independent reviewers. Descriptive statistics were used. RESULTS: Response rate was 62% and 56 AUFs in 53 patients were reported between 2003 and 2018. The estimated incidence of AUF in The Netherlands in this time period is 3.5 AUFs per year. Hematuria was observed in all patients; 9% intermittent microhematuria, and 91% presenting with, or building up to massive hematuria. For the final diagnosis, angiography was the most efficient modality, confirming diagnosis in 58%. Treatment comprised predominantly endovascular intervention. CONCLUSION: The diagnosis AUF should be considered in patients with persistent intermittent or massive hematuria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-021-03910-3

    Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

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    We report the discovery of very-high-energy (VHE) gamma-ray emission of the binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the H.E.S.S. experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a gamma-ray signal from the binary system was detected with a total significance above 13 sigma. The flux was found to vary significantly on timescales of days which makes PSR B1259-63 the first variable galactic source of VHE gamma-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F_0(E/1 TeV)^-Gamma with a photon index Gamma = 2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys) 10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June 2005, replace: document unchanged, replaced author field in astro-ph entry - authors are all members of the H.E.S.S. collaboration and three additional authors (99+3, see document

    Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

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    Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654

    Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

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    Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia

    Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder

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    Aim: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. Methods: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. Results: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P <.001). Higher sum trough concentrations also predicted more sedation (P <.05), higher prolactin levels (P <.001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P <.01). Conclusion: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems

    A low level of extragalactic background light as revealed by big gamma-rays from blazars

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    The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light1. An alternative approach2, 3, 4, 5 is to study the absorption features imprinted on the -ray spectra of distant extragalactic objects by interactions of those photons with the background light photons6. Here we report the discovery of -ray emission from the blazars7 H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies8. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources—in particular from the first stars formed9. This result also indicates that intergalactic space is more transparent to -rays than previously thought

    Discovery of extended VHE gamma-ray emission from the asymmetric pulsar wind nebula in MSH 15-52 with H.E.S.S

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    The Supernova Remnant MSH 15-52 has been observed in very high energy (VHE) gamma-rays using the H.E.S.S. 4-telescope array located in Namibia. A gamma-ray signal is detected at the 25 sigma level during an exposure of 22.1 hours live time. The image reveals an elliptically shaped emission region around the pulsar PSR B1509-58, with semi-major axis 6' in the NW-SE direction and semi-minor axis 2' approximately. This morphology coincides with the diffuse pulsar wind nebula as observed at X-ray energies by ROSAT. The overall energy spectrum from 280 GeV up to 40 TeV can be fitted by a power law with photon index Gamma = 2.27 +/- 0.03(stat.) +/- 0.20(syst.). The detected emission can be plausibly explained by inverse Compton scattering of accelerated relativistic electrons with soft photons.Comment: 5 pages, 3 figures, accepted by A&A letter

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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