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Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development.
The nuclear farnesoid X receptor (FXR) and the enzyme soluble epoxide hydrolase (sEH) are validated molecular targets to treat metabolic disorders such as non‐alcoholic steatohepatitis (NASH). Their simultaneous modulation in vivo has demonstrated a triad of anti‐NASH effects and thus may generate synergistic efficacy. Here we report dual FXR activators/sEH inhibitors derived from the anti‐asthma drug Zafirlukast. Systematic structural optimization of the scaffold has produced favorable dual potency on FXR and sEH while depleting the original cysteinyl leukotriene receptor antagonism of the lead drug. The resulting polypharmacological activity profile holds promise in the treatment of liver‐related metabolic diseases.
Nicht nur in den dogmatischen Disziplinen der Rechtswissenschaft, sondern auch in der Rechtsgeschichte als einem sog. Grundlagenfach sind wissenschaftliche Reflexionen über die Methode des eigenen Fachs weitgehend Desiderat: "Methode hat man, über Methode spricht man nicht!" Diese Haltung verbindet sich in der Rechtsgeschichte noch immer allzu oft mit der Absicht, zeigen zu wollen, "wie es eigentlich gewesen" (Ranke). Insgesamt scheint sich an der Beobachtung von Heinrich Mitteis aus dem Jahr 1947, die Rechtsgeschichte habe sich "methodischen Fragen gegenüber gleichgültiger verhalten als andere Teile der Geschichtswissenschaft" und ihr Werk bislang mit "nachtwandlerischer Selbstsicherheit" verrichtet, nichts fundamental geändert zu haben. So verwundert es nicht, dass sich die rechtsgeschichtliche Forschung bisweilen dem Vorwurf ausgesetzt sieht, methodisch wenig innovativ vorzugehen. ...
In der aktuellen verwaltungsrechtswissenschaftlichen Literatur konnte noch immer keine Einigung über den Regulierungsbegriff erzielt werden. Durchzusetzen scheint sich eine Definition, die unter Regulierung "jede gewollte staatliche Beeinflussung gesellschaftlicher Prozesse [versteht], die einen spezifischen, aber über den Einzelfall hinausgehenden Ordnungszweck verfolgt und dabei im Recht zentrales Medium und Grenze findet". Basierend auf einem derartigen Verständnis von Regulierung unterschied W. Hoffmann-Riem 1990 zwischen drei Regulierungsformen und prägte für sie die Begriffe staatlich imperative Regulierung, staatlich regulierte Selbstregulierung und private Selbstregulierung. Dabei soll sich die regulierte Selbstregulierung als Mittelkategorie dadurch auszeichnen, dass sich der Staat einerseits eine spezifisch gesellschaftliche Handlungslogik zunutze macht, andererseits aber den angestrebten Ordnungszweck (mit-)bestimmen kann. ..
A modern linear accelerator of ions is a long chain of different accelerating-focusing structures. The design of new linacs, as well as an upgrade and optimization of operating facilities, requires precise and reliable beam matching with the subsequent sections. Proper matching of the beam to the channel allows to improve the performance of the whole linac and to reduce the specific costs. Additionally it helps to avoide particle loss in high energy high intensity linacs. Generally a matching algorithm combines precisely measured or calculated accelerating-focusing external fields and experimentally obtained details of the beam parameters with an advanced code for beam dynamics simulations including space charge effects. Experimental results are introduced into a code as input data. The described algorithm has already been successfully implemented for several GSI projects: an upgrade of the GSI heavy ion linac UNILAC, an ion linac for the cancer therapy, the proton linac for the FAIR facility, a facility for laser acceleration of ions and others. Measured data and results of beam dynamics simulations leading to an achieved improvement of the linac performance are presented.
The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Discoveries of new species often depend on one or a few specimens, leading to delays as researchers wait for additional context, sometimes for decades. There is currently little professional incentive for a single expert to publish a stand-alone species description. Additionally, while many journals accept taxonomic descriptions, even specialist journals expect insights beyond the descriptive work itself. The combination of these factors exacerbates the issue that only a small fraction of marine species are known and new discoveries are described at a slow pace, while they face increasing threats from accelerating global change. To tackle this challenge, this first compilation of Ocean Species Discoveries (OSD) presents a new collaborative framework to accelerate the description and naming of marine invertebrate taxa that can be extended across all phyla. Through a mode of publication that can be speedy, taxonomy-focused and generate higher citation rates, OSD aims to create an attractive home for single species descriptions. This Senckenberg Ocean Species Alliance (SOSA) approach emphasises thorough, but compact species descriptions and diagnoses, with supporting illustrations and with molecular data when available. Even basic species descriptions carry key data for distributions and ecological interactions (e.g., host-parasite relationships) besides universally valid species names; these are essential for downstream uses, such as conservation assessments and communicating biodiversity to the broader public.This paper presents thirteen marine invertebrate taxa, comprising one new genus, eleven new species and one re-description and reinstatement, covering wide taxonomic, geographic, bathymetric and ecological ranges. The taxa addressed herein span three phyla (Mollusca, Arthropoda, Echinodermata), five classes, eight orders and twelve families. Apart from the new genus, an updated generic diagnosis is provided for four other genera. The newly-described species of the phylum Mollusca are Placiphorella methanophila Vončina, sp. nov. (Polyplacophora, Mopaliidae), Lepetodrilus marianae Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Lepetodrilidae), Shinkailepas gigas Chen, Watanabe & Tsuda, sp. nov. (Gastropoda, Phenacolepadidae) and Lyonsiella illaesa Machado & Sigwart, sp. nov. (Bivalvia, Lyonsiellidae). The new taxa of the phylum Arthropoda are all members of the subphylum Crustacea: Lepechinella naces Lörz & Engel, sp. nov. (Amphipoda, Lepechinellidae), Cuniculomaera grata Tandberg & Jażdżewska, gen. et sp. nov. (Amphipoda, Maeridae), Pseudionella pumulaensis Williams & Landschoff, sp. nov. (Isopoda, Bopyridae), Mastigoniscus minimus Wenz, Knauber & Riehl, sp. nov. (Isopoda, Haploniscidae), Macrostylis papandreas Jonannsen, Riehl & Brandt, sp. nov. (Isopoda, Macrostylidae), Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. (Isopoda, Nannoniscidae) and Apseudopsis daria Esquete & Tato, sp. nov. (Tanaidacea, Apseudidae). In the phylum Echinodermata, the reinstated species is Psychropotes buglossa E. Perrier, 1886 (Holothuroidea, Psychropotidae).The study areas span the North and Central Atlantic Ocean, the Indian Ocean and the North, East and West Pacific Ocean and depths from 5.2 m to 7081 m. Specimens of eleven free-living and one parasite species were collected from habitats ranging from an estuary to deep-sea trenches. The species were illustrated with photographs, line drawings, micro-computed tomography, confocal laser scanning microscopy and scanning electron microscopy images. Molecular data are included for nine species and four species include a molecular diagnosis in addition to their morphological diagnosis.The five new geographic and bathymetric distribution records comprise Lepechinella naces Lörz & Engel, sp. nov., Cuniculomaera grata Tandberg & Jażdżewska, sp. nov., Pseudionella pumulaensis Williams & Landschoff, sp. nov., Austroniscus indobathyasellus Kaiser, Kniesz & Kihara, sp. nov. and Psychropotes buglossa E. Perrier, 1886, with the novelty spanning from the species to the family level. The new parasite record is Pseudionella pumulaensis Williams & Landschoff, sp. nov., found in association with the hermit crab Pagurus fraserorum Landschoff & Komai, 2018.