The psychometric properties of the German version of the WHOQOL-OLD in the German population aged 60 and older

Background: The WHOQOL-OLD is an instrument for the assessment of subjective quality of life in elderly people. It is based on the WHO definition of quality of life and is available in more than 20 languages. However, in most countries, the psychometric properties of the WHOQOL-OLD have been assessed only on the basis of small local samples and not in representative studies. In this study, the psychometric properties of the WHOQOL-OLD are evaluated based on a representative sample of Germany\''s elderly population. Methods: Face-to-face interviews with 1133 respondents from the German population aged 60 years and older were conducted. Quality of life was assessed by means of the WHOQOL-BREF, the WHOQOL-OLD and the SF12. Moreover, the GDS, the DemTect and the IADL were applied for the assessment of depressive symptoms, cognitive capacities and capacity for carrying out daily activities. Psychometric properties of the WHOQOL-OLD were evaluated by means of classical and probabilistic test theory, confirmatory factor analysis and multivariate regression model.Results: Cronbach\''s alpha was found to be above 0.85 for four and above .75 for two of the six facets of the WHOQOL-OLD. IRT analyses indicated that all items of the WHOQOL-OLD contribute considerably to the measurement of the associated facets. While the six-facet structure of the WHOQOL-OLD was well supported by the results of the confirmatory factor analysis, a common latent factor for the WHOQOL-OLD total scale could not be identified. Correlations with other quality of life measures and multivariate regression models with GDS, IADL and the DemTect indicate a good criterion validity of all six WHOQOL-OLD facets.Conclusions: Study results confirm that the good psychometric properties of the WHOQOL-OLD that have been found in international studies could be replicated in a representative study of the German population. These results suggest that the WHOQOL-OLD is an instrument that is well suited to identify the needs and the wishes of an aging population

Introducing LoCo, a Logic for Configuration Problems

In this paper we present the core of LoCo, a logic-based high-level representation language for expressing configuration problems. LoCo shall allow to model these problems in an intuitive and declarative way, the dynamic aspects of configuration notwithstanding. Our logic enforces that configurations contain only finitely many components and reasoning can be reduced to the task of model construction.Comment: In Proceedings LoCoCo 2011, arXiv:1108.609

aspcud: A Linux Package Configuration Tool Based on Answer Set Programming

We present the Linux package configuration tool aspcud based on Answer Set Programming. In particular, we detail aspcud's preprocessor turning a CUDF specification into a set of logical facts.Comment: In Proceedings LoCoCo 2011, arXiv:1108.609

(Re)configuration based on model generation

Reconfiguration is an important activity for companies selling configurable products or services which have a long life time. However, identification of a set of required changes in a legacy configuration is a hard problem, since even small changes in the requirements might imply significant modifications. In this paper we show a solution based on answer set programming, which is a logic-based knowledge representation formalism well suited for a compact description of (re)configuration problems. Its applicability is demonstrated on simple abstractions of several real-world scenarios. The evaluation of our solution on a set of benchmark instances derived from commercial (re)configuration problems shows its practical applicability.Comment: In Proceedings LoCoCo 2011, arXiv:1108.609

Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man’s risk of disease by 10% (OR 1.10 [1.04–1.16], p,261023), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p,161023), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p,0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.261025). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.This work was partially funded by the Portuguese Foundation for Science and Technology FCT/MCTES (PIDDAC) and co-financed by European funds (FEDER) through the COMPETE program, research grant PTDC/SAU-GMG/101229/2008. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT. AML is the recipient of a postdoctoral fellowship from FCT (SFRH/BPD/73366/2010). CO is supported by a grant from the United States National Institutes of Health (R01 HD21244), JDS is supported by Damon Runyon Clinical Investigator Award, Alex's Lemonade Stand Foundation Epidemiology Award, and the Eunice Kennedy Shriver Children's Health Research Career Development Award NICHD 5K12HD001410. Support for humans studies and specimens were provided by the NIH/NIDDK George M. O'Brien Center for Kidney Disease Kidney Translational Research Core (P30DK079333) grant to Washington University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The anti-absence effect of mGlu5 receptor amplification with VU0360172 is maintained during and after antiepileptogenesis

Ethosuximide (ETX) has become the drug of choice in the treatment of patients with absence seizures taking into account both its efficacy, tolerability and antiepileptogenic properties. However, 47% of subjects treated with ETX failed in therapy, and most antiepileptic drugs have cognitive side effects. VU0360172, a positive allosteric modulator (PAM) of mGluR5, acutely and chronically administered decreased seizures dose dependently in rats of the WAG/Rij strain, a genetic absence model. Here it is investigated whether anti-epileptogenesis induced by ETX alters the sensitivity of VU0360172 as an anti-absence drug, and cognition is affected during and after chronic ETX treatment. Method: Male WAG/Rij rats were chronically treated with ETX for 4 months. EEG’s were recorded during and after treatment as well as challenged with VU0360172. Rats were also periodically exposed to a cue discrimination learning task in a Y-maze. mGlu5 receptors were quantified with Western Blot. Results: Antiepileptogenesis was successfully induced by ETX and VU0360172 showed a time and dose dependent anti-absence action. However, chronic ETX treated rats showed a decrease in absences both during and after the end treatment, without clear time and dose related effects. The decrease of sensitivity for VU0360172 was not accompanied by a change in mGluR5 expression in cortex and thalamus. Chronic ETX enhanced motivation to collect sucrose pallets and this was followed by an increase in cued discrimination learning. It is concluded that VU0360172 keeps its antiabsence effects after chronic treatment. Moreover, its differential effects in the two groups cannot be explained by a simple receptor down regulation suggesting a more downstream interaction between ETX and mGluR5. The cognitive enhancing effects of ETX, as found at the end of the experiment might be mediated to the antidepressant action of ETX as expressed by an increase in the rewarding properties of sucrose pallets

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

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

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead