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Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth’s biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented “next-generation biomonitoring” by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P< 5 x 10(-8). In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Gilbert et al. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Hintergrund
Lumbale Ruckenschmerzen und ihre Neigung zur Chronifizierung stellen nicht nur in der Allgemeinbevolkerung, sondern auch im Leistungssport ein bedeutendes Gesundheitsproblem dar. Im Gegensatz zu Nichtathleten ist die Erforschung psychosozialer Risikofaktoren sowie von Screeningfragebogen, die moglichst fruhzeitig die Entwicklung chronischer Schmerzen erkennen und vorhersagen konnen, im Leistungssport noch in den Anfangen. Das vorliegende systematische Review gibt einen uberblick uber den Stand der Risikofaktorenforschung in beiden Feldern und untersucht die pradiktive Qualitat verschiedener Screeningfragebogen bei Nichtathleten.
Methodik
Die Literatursuche erfolgte zwischen Marz und Juni 2016 in den Datenbanken MEDLINE, PubMed und PsycINFO mit den Suchbegriffen psychosocial screening, low back pain, sciatica und prognosis, athletes. Eingeschlossen wurden prospektive Studien an Patienten mit lumbalen Ruckenschmerzen mit und ohne Ausstrahlung in das Bein, 18Jahre und mit einem Follow-up von mindestens 3-monatiger Dauer.
Ergebnisse
In das Review zu Screeninginstrumenten wurden 16Studien einbezogen. Alle waren an klinischen Stichproben der Allgemeingesellschaft durchgefuhrt worden. Zu den am haufigsten publizierten Screeningfragebogen gehoren der orebro Musculoskeletal Pain Screening Questionnaire (oMPSQ) mit einer zufriedenstellenden Fruherkennung der Wiederherstellung der Arbeitsfahigkeit sowie das STarT Back Screening Tool (SBT) mit guter Vorhersage schmerzbedingter Beeintrachtigung. Fur die Vorhersage kunftiger Schmerzen eignen sich die Risikoanalyse der Schmerzchronifizierung (RISC-R) und der Heidelberger Kurzfragebogen (HKF).
Schlussfolgerungen
Psychosoziale Risikofaktoren fur chronische Ruckenschmerzen, wie z.B. chronischer Stress, ungunstige Schmerzverarbeitung und depressive Stimmungslagen, werden zunehmend auch im Leistungssport erkannt. Screeninginstrumente, die sich in der Allgemeingesellschaft als hinreichend vorhersagestark erwiesen haben, werden aktuell im MiSpEx-Forschungsverbund auf ihre Eignung uberpruft.
Psychosocial risk factors for chronic back pain in the general population and in competitive sports
(2018)
Lumbar back pain and the high risk of chronic complaints is not only an important health concern in the general population but also in high performance athletes. In contrast to non-athletes, there is a lack of research into psychosocial risk factors in athletes. Moreover, the development of psychosocial screening questionnaires that would be qualified to detect athletes with a high risk of chronicity is in the early stages. The purpose of this review is to give an overview of research into psychosocial risk factors in both populations and to evaluate the performance of screening instruments in non-athletes. The databases MEDLINE, PubMed, and PsycINFO were searched from March to June 2016 using the keywords "psychosocial screening", "low back pain", "sciatica" and "prognosis", "athletes". We included prospective studies conducted in patients with low back pain with and without radiation to the legs, aged ae<yen>18 years and a follow-up of at least 3 months. We identified 16 eligible studies, all of them conducted in samples of non-athletes. Among the most frequently published screening questionnaires, the A-rebro Musculoskeletal Pain Screening Questionnaire (A-MPSQ) demonstrated a sufficient early prediction of return to work and the STarT Back Screening Tool (SBT) revealed acceptable performance predicting pain-related impairment. The prediction of future pain was sufficient with the Risk Analysis of Back Pain Chronification (RISC-BP) and the Heidelberg Short Questionnaire (HKF). Psychosocial risk factors of chronic back pain, such as chronic stress, depressive mood, and maladaptive pain processing are becoming increasingly more recognized in competitive sports. Screening instruments that have been shown to be predictive in the general population are currently being tested for suitability in the German MiSpEx research consortium.
Myriapods (e. g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.