Studying the spatial-social interface requires tools that distinguish between social and spatial drivers of interactions. Testing hypotheses about the factors determining animal interactions often involves comparing observed interactions with reference or \'null\' models. One approach to accounting for spatial drivers of social interactions in reference models is randomizing animal movement paths to decouple spatial and social phenotypes while maintaining environmental effects on movements. Here, we update a reference model that detects social attraction above the effect of spatial constraints. We explore the use of our \'wrap-around\' method and compare its performance to the previous approach using agent-based simulations. The wrap-around method provides reference models that are more similar to the original tracking data, while still distinguishing between social and spatial drivers. Furthermore, the wrap-around approach results in fewer false-positives than its predecessor, especially when animals do not return to one place each night but change movement foci, either locally or directionally. Finally, we show that interactions among GPS-tracked griffon vultures (Gyps fulvus) emerge from social attraction rather than from spatial constraints on their movements. We conclude by highlighting the biological situations in which the updated method might be most suitable for testing hypotheses about the underlying causes of social interactions. This article is part of the theme issue \'The spatial-social interface: a theoretical and empirical integration\'.

暂无摘要。

OBJECTIVE: This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy.
METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up.
RESULTS: Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months.
CONCLUSIONS: Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies.
BACKGROUND: ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).

BACKGROUND: Observational studies have found a correlation between the levels of blood lipids and the development and progression of endometriosis (EM). However, the causality and direction of this correlation is unclear. This study aimed to examine the bidirectional connection between lipid profiles and the risk of EM using publicly available genome-wide association study (GWAS) summary statistics.
METHODS: Eligible exposure variables such as levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were selected using a two-sample Mendelian randomization (MR) analysis method following a series of quality control procedures. Data on EM were obtained from the publicly available Finnish database of European patients. Inverse variance weighted (IVW), MR Egger, weighted median, and weighted mode methods were used to analyze the causal relationship between lipid exposure and EM, exclude confounders, perform sensitivity analyses, and assess the stability of the results. Reverse MR analyses were performed with EM as exposure and lipid results as study outcomes.
RESULTS: IVW analysis results identified HDL as a protective factor for EM, while TG was shown to be a risk factor for EM. Subgroup analyses based on the site of the EM lesion identified HDL as a protective factor for EM of the uterus, while TG was identified a risk factor for the EM of the fallopian tube, ovary, and pelvic peritoneum. Reverse analysis did not reveal any effect of EM on the levels of lipids.
CONCLUSIONS: Blood lipids, such as HDL and TG, may play an important role in the development and progression of EM. However, EM does not lead to dyslipidemia.

Criteria for assessment of the significance of scientific articles are presented. The focus is on research design and methodology, illustrated by the classical study on prehospital volume treatment of severely injured individuals with penetrating torso injuries by Bickell et al. (1994). A well-thought out research design is crucial for the success of a scientific study and is documented in a study protocol beforehand. A hypothesis is a provisional explanation or prediction and must be testable, falsifiable, precise, and relevant. There are various types of randomization methods, with the randomized controlled trial being the gold standard for clinical interventional studies. When reading a scientific article it is important to verify whether the research design and setting align with the research question and whether potential sources of error have been considered and controlled. Critical scrutiny should also be applied to references, the funding and expertise of the researchers.
UNASSIGNED: Kriterien zur Einordnung der Aussagekraft wissenschaftlicher Artikel werden vorgestellt. Der Fokus liegt auf Forschungsdesign und Methodik, die anhand der klassischen Studie zur prähospitalen Volumentherapie bei Schwerverletzten mit penetrierenden Torsoverletzungen von Bickell et al. (1994) erläutert werden. Ein sorgfältig durchdachtes Forschungsdesign entscheidet über den Erfolg einer wissenschaftlichen Studie und wird vorab im Studienprotokoll festgehalten. Eine Hypothese ist eine vorläufige Erklärung oder Vorhersage und muss test-, falsifizierbar, präzise und relevant sein. Es gibt verschiedene Randomisierungsarten. Die randomisierte kontrollierte Studie ist der Goldstandard klinischer Interventionsstudien. Beim Lesen einer wissenschaftlichen Arbeit sollte kontrolliert werden, ob Forschungsdesign und -setting zur Forschungsfrage passen, und ob Fehlerquellen bedacht und kontrolliert wurden. Kritisch prüfen lassen sich auch Literaturangaben, Finanzierung und Expertise der Forschenden.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

As the volume of next generation sequencing data increases, an urgent need for algorithms to efficiently process the data arises. Universal hitting sets (UHS) were recently introduced as an alternative to the central idea of minimizers in sequence analysis with the hopes that they could more efficiently address common tasks such as computing hash functions for read overlap, sparse suffix arrays, and Bloom filters. A UHS is a set of k-mers that hit every sequence of length L, and can thus serve as indices to L-long sequences. Unfortunately, methods for computing small UHSs are not yet practical for real-world sequencing instances due to their serial and deterministic nature, which leads to long runtimes and high memory demands when handling typical values of k (e.g. k>13). To address this bottleneck, we present two algorithmic innovations to significantly decrease runtime while keeping memory usage low: (i) we leverage advanced theoretical and architectural techniques to parallelize and decrease memory usage in calculating k-mer hitting numbers; and (ii) we build upon techniques from randomized Set Cover to select universal k-mers much faster. We implemented these innovations in PASHA, the first randomized parallel algorithm for generating nearoptimal UHSs, which newly handles k>13. We demonstrate empirically that PASHA produces sets only slightly larger than those of serial deterministic algorithms; moreover, the set size is provably guaranteed to be within a small constant factor of the optimal size. PASHA\'s runtime and memory-usage improvements are orders of magnitude faster than the current best algorithms. We expect our newly-practical construction of UHSs to be adopted in many high-throughput sequence analysis pipelines.

A random initialization of the search particles is a strong argument in favor of the deployment of nature-inspired metaheuristic algorithms when the knowledge of a good initial guess is lacked. This article analyses the impact of the type of randomization on the working of algorithms and the acquired solutions. In this study, five different types of randomizations are applied to the Accelerated Particle Swarm Optimization (APSO) and Squirrel Search Algorithm (SSA) during the initializations and proceedings of the search particles for selective harmonics elimination (SHE). The types of randomizations include exponential, normal, Rayleigh, uniform, and Weibull characteristics. The statistical analysis shows that the type of randomization does impact the working of optimization algorithms and the fittest value of the objective function.

暂无摘要。

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies.
OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring.
METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022.
RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted.
CONCLUSIONS: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.