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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.
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
Extensive black shale deposits formed in the Early Cretaceous South Atlantic, supporting the notion that this emerging ocean basin was a globally important site of organic carbon burial. The magnitude of organic carbon burial in marine basins is known to be controlled by various tectonic, oceanographic, hydrological, and climatic processes acting on different temporal and spatial scales, the nature and relative importance of which are poorly understood for the young South Atlantic. Here we present new bulk and molecular geochemical data from an Aptian–Albian sediment record recovered from the deep Cape Basin at Deep Sea Drilling Project (DSDP) Site 361, which we combine with general circulation model results to identify driving mechanisms of organic carbon burial. A multimillion-year decrease (i.e., Early Aptian–Albian) in organic carbon burial, reflected in a lithological succession of black shale, gray shale, and red beds, was caused by increasing bottom water oxygenation due to abating hydrographic restriction via South Atlantic–Southern Ocean gateways. These results emphasize basin evolution and ocean gateway development as a decisive primary control on enhanced organic carbon preservation in the Cape Basin at geological timescales (> 1 Myr). The Early Aptian black shale sequence comprises alternations of shales with high (> 6 %) and relatively low (∼ 3.5 %) organic carbon content of marine sources, the former being deposited during the global Oceanic Anoxic Event (OAE) 1a, as well as during repetitive intervals before and after OAE 1a. In all cases, these short-term intervals of enhanced organic carbon burial coincided with strong influxes of sediments derived from the proximal African continent, indicating closely coupled climate–land–ocean interactions. Supported by our model results, we show that fluctuations in weathering-derived nutrient input from the southern African continent, linked to changes in orbitally driven humidity and aridity, were the underlying drivers of repetitive episodes of enhanced organic carbon burial in the deep Cape Basin. These results suggest that deep marine environments of emerging ocean basins responded sensitively and directly to short-term fluctuations in riverine nutrient fluxes. We explain this relationship using the lack of wide and mature continental shelf seas that could have acted as a barrier or filter for nutrient transfer from the continent into the deep ocean.
The Weissert Event ~133 million years ago marked a profound global cooling that punctuated the Early Cretaceous greenhouse. We present modelling, high-resolution bulk organic carbon isotopes and chronostratigraphically calibrated sea surface temperature (SSTs) based on an organic paleothermometer (the TEX86 proxy), which capture the Weissert Event in the semi-enclosed Weddell Sea basin, offshore Antarctica (paleolatitude ~54 °S; paleowater depth ~500 meters). We document a ~3–4 °C drop in SST coinciding with the Weissert cold end, and converge the Weddell Sea data, climate simulations and available worldwide multi-proxy based temperature data towards one unifying solution providing a best-fit between all lines of evidence. The outcome confirms a 3.0 °C ( ±1.7 °C) global mean surface cooling across the Weissert Event, which translates into a ~40% drop in atmospheric pCO2 over a period of ~700 thousand years. Consistent with geologic evidence, this pCO2 drop favoured the potential build-up of local polar ice.
Geometrical frustration among interacting spins combined with strong quantum fluctuations destabilize long-range magnetic order in favor of more exotic states such as spin liquids. By following this guiding principle, a number of spin liquid candidate systems were identified in quasi-two-dimensional (quasi-2D) systems. For 3D, however, the situation is less favorable as quantum fluctuations are reduced and competing states become more relevant. Here we report a comprehensive study of thermodynamic, magnetic and dielectric properties on single crystalline and pressed-powder samples of PbCuTe2O6, a candidate material for a 3D frustrated quantum spin liquid featuring a hyperkagome lattice. Whereas the low-temperature properties of the powder samples are consistent with the recently proposed quantum spin liquid state, an even more exotic behavior is revealed for the single crystals. These crystals show ferroelectric order at TFE ≈ 1 K, accompanied by strong lattice distortions, and a modified magnetic response—still consistent with a quantum spin liquid—but with clear indications for quantum critical behavior.
Rationale: Steroid refractory graft-vs-host disease (sr-GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo-HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr-GvHD.
Objectives: We studied the effects of FMT on sr-GvHD in allo-HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre- and post-FMT (day -14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre- and post-FMT by 16S rRNA sequencing.
Results: Post-FMT, we observed no intervention-associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis—each 3/11 and vomiting—1/11). Stool frequencies and volumes were significantly reduced [pre- vs post-FMT (d14): P < .05, respectively] as well as clear attenuation regarding both grading and staging of sr-GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post-FMT.
Conclusions: In our study, we observed positive effects on sr-GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr-GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action.
When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here, we show in awake macaque area V1 that both repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects show some persistence on the timescale of minutes. Gamma increases are specific to the presented stimulus location. Further, repetition effects on gamma and on firing rates generalize to images of natural objects. These findings support the notion that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters.
Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.