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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.

ABSTRACT Among randomized numerical linear algebra strategies, so‐called sketching procedures are emerging as effective reduction means to accelerate the computation of Krylov subspace methods for, for example, the solution of linear systems, eigenvalue computations, and the approximation of matrix functions. While there is plenty of experimental evidence showing that sketched Krylov solvers may dramatically improve performance over standard Krylov methods, especially when combined with a truncated orthogonalization step, many features of these schemes are still unexplored. We derive a new sketched Arnoldi‐type relation that allows us to obtain several different new theoretical results. These lead to an improvement of our understanding of sketched Krylov methods, in particular by explaining why the frequently occurring sketched Ritz values far outside the spectral region of A$$ A $$ do not negatively influence the convergence of sketched Krylov methods for f(A)b$$ f(A)b $$. Our findings also help to identify, among several possible equivalent formulations, the most suitable sketched approximations according to their numerical stability properties. These results are also employed to analyze the error of sketched Krylov methods in the approximation of the action of matrix functions, significantly contributing to the theory available in the current literature. [ABSTRACT FROM AUTHOR]

Objective This study investigated the effectiveness of supramaximal high-intensity interval training (supramaximal HIT) on muscle capacities and physical function compared to moderate-intensity training (MIT) for older adults. Methods Sixty-eight older adults (66–79 years, 56% women), not engaged in regular exercise, were randomised to 3 months of twice-weekly supramaximal HIT (20 minutes including 10 × 6-second intervals) or MIT (40 minutes including 3 × 8-minute intervals). Both groups performed the training on stationary bicycles in a group setting. Target intensity was watt-controlled, with standardised cadence and individualised resistance. Outcomes analysed with linear-mixed models included leg power (Nottingham Power Rig), hand grip strength (Jamar dynamometer), static and dynamic balance (One leg stance, 30-second step test), chair stand (30-second chair stand), and anaerobic cycling performance (modified Borg Cycle Strength Test). Results Baseline values were (supramaximal HIT/MIT, mean ± SD) leg power 198 ± 60/189 ± 53 W, hand grip strength 4.2 ± 1.0/4.3 ± 1.1 N/kg, static balance 64 ± 41/62 ± 41 s, dynamic balance 39 ± 7/38 ± 5 steps, chair stands 22 ± 6/22 ± 6 and anaerobic cycling performance 224 ± 60/217 ± 55 W. At 3-month follow-up, a between-group difference in favour of supramaximal HIT [95% CI] was observed in anaerobic cycling performance of 19[3;35] W. Within-group mean changes for supramaximal HIT/MIT were for leg power 8.4[0.9;15.8]/6.0[−1.3;13.3] W, hand grip strength 0.14[0.00;0.27]/0.13[−0.01;0.26] N/kg, static balance 11[3;20]/10[1;18] s, dynamic balance 1.6[0.3;2.8]/2.3[1.1;3.6] steps, 2.1[1.1;3.1]/1.4[0.4;2.3] chair stands and anaerobic cycling performance 31.3[19.6;43.0]/12.0[0.4;23.5] W. Conclusion Supramaximal HIT showed superior effect on anaerobic cycling performance when compared to MIT. Additionally, the results indicate that supramaximal HIT is comparably beneficial as MIT in terms of effects on muscle capacity and physical function for older adults. [ABSTRACT FROM AUTHOR]

Background Falls have high socioeconomic costs. Information and communication technologies may support provision and monitoring of multisensory (MSR) physiotherapy programmes. The HOLOBalance platform used augmented reality holograms to provide patient-centred, individualised MSR. Objectives To determine the platform's safety, acceptability and feasibility, investigate functional gait and dynamic balance benefits and provide data for a definitive trial. Design and setting Single-blinded pilot randomised controlled feasibility study. Interventions were conducted at clinical sites or participants' homes in three European countries. Participants Community-dwelling older adults (median age 73 years; 64.2% female) at risk of falls were enrolled (May 2020-August 2021). Methods Participants were randomised to an 8-week clinic or home-based telerehabilitation MSR or OTAGO (control group) programme. Compliance, satisfaction, and adverse events determined feasibility. Clinical outcomes, assessed (blinded) within one-week prior to and post-intervention, included functional gait assessment (FGA), Mini BESTest and cognitive function. Results Randomisation to completion rate was 76.15% with 109 participants recruited (n = 289 screened). Drop-out rate was similar between groups. Adverse events were reported (n = 3) in the control group. Sixty-nine percent would recommend the HOLOBalance intervention. Findings were similar for the home and clinic-based arms of each intervention; data was combined for analysis. FGA (95%CI [1.63, 4.19]) and Mini-BESTest (95%CI [1.46, 3.93]) showed greater improvement in the HOLOBalance group with a clinically meaningful change of 4/30 noted for the FGA. Conclusions HOLObalance was feasible to implement and acceptable to older adults at risk of falls, with FGA and Mini-BEST improvements exceeding those for the OTAGO programme. A definitive trial is warranted. [ABSTRACT FROM AUTHOR]

We consider a setting with agents that have preferences over alternatives and are partitioned into disjoint districts. The goal is to choose one alternative as the winner using a mechanism which first decides a representative alternative for each district based on a local election with the agents therein as participants, and then chooses one of the district representatives as the winner. Previous work showed bounds on the distortion of a specific class of deterministic plurality-based mechanisms depending on the available information about the preferences of the agents in the districts. In this paper, we first consider the whole class of deterministic mechanisms and show asymptotically tight bounds on their distortion. We then initiate the study of the distortion of randomized mechanisms in distributed voting and show bounds based on several informational assumptions, which in many cases turn out to be tight. Finally, we also experimentally compare the distortion of many different mechanisms of interest using synthetic and real-world data. [ABSTRACT FROM AUTHOR]

In June–July 2022, the Randomization Working Group () conducted an online survey on the current practices in the application of randomization in clinical trials. Of 145 unique respondents, 137 (94.5%) identified themselves as statisticians. The majority of respondents were from academia and pharmaceutical companies. Permuted block randomization, with or without stratification, was the most frequently chosen method of randomization for RCTs. Interactive Web-Based Response Systems (IWRS) and "in-house" or a combination of "in-house and outsourced" randomization models were found to be most common in practice. Over 80% of respondents perceived some challenges to adoption of new randomization methods that may have more desirable properties. Over 80% of respondents identified opportunities for improving current practice, including education/training, development of standards/guidance on randomization, and adoption of validated software for generating randomization sequences. In summary, practitioners acknowledge the pivotal role of randomization in clinical trials. There are some perceived challenges to successful implementation of randomization, and there are opportunities for improving practice. [ABSTRACT FROM AUTHOR]

The investigator in a randomized open-label single-center trial knows the treatment assignments of all randomized subjects and thus can introduce a selection bias in the study results by allocating subjects with a better prognosis when he guesses the next allocation is to the experimental group. When the allocation procedure is known to the investigator, Blackwell and Hodges demonstrated that the truncated binomial design of the size N, where subjects are allocated at random with probability ½ until one of the treatment arms has N / 2 subjects, minimizes the selection bias among all 1:1 allocation procedures that assign N / 2 subjects to each treatment. In this article we demonstrate that for any allocation space symmetric with respect to the two treatments, the selection bias is also minimized with the procedure that allocates subjects with probability ½ whenever allocation to both treatments is allowed—the big stick design. We propose to control both the balance in treatment assignments and the selection bias by specifying the allocation space with acceptable, possibly increasing with time, imbalance and using the big stick randomization within it. We show how the selection bias can be further reduced when the investigator is not aware of the allocation procedure. [ABSTRACT FROM AUTHOR]

This article provides an introduction to randomized response polling, a technique which was designed to allow for questioning on sensitive issues while protecting the respondent's privacy and avoiding social desirability bias. It is described in terms that are suitable for presentation and use in any classroom environment. Instructions for plain users are included, along with the results of a small in-class implementation. The underpinnings of the method, which are laid out for the statistically savvy, illustrate the tradeoff between data acquisition and privacy protection. A few suitable references are also included for those who wish to dig further into the subject. for this article are available online. [ABSTRACT FROM AUTHOR]

Using a variant of the hide‐and‐seek game, we show in three studies that self‐enhancement can help or hinder strategic thinking. In this guessing game, one player chooses a number while another player tries to guess it. Each player does this either in a random fashion (throwing a mental die) or by active thinking. The structure of the game implies that guessers benefit from thinking about a number, whereas choosers are disadvantaged. Yet, regardless of their role, respondents prefer to actively think about a number. For choosers, the belief they can outthink the opponent amounts to self‐enhancement, whereas for guessers, the same belief can be rationally justified. We discuss the implications of the findings for theories of strategic cognition and applications to real‐world contexts. [ABSTRACT FROM AUTHOR]

This article presents the results of an RCT assessing the impact of a Shared Book Reading (SBR) intervention that targeted children aged 4 attending kindergarten. We selected a large, random sample of families living in the city of Paris and provided parents of treated classes with free books for children, information on the benefits of book reading and tips for effective reading practices. We measured book reading frequency and children's vocabulary before and after this intervention among treated and control children, and we found evidence of positive treatment effects on book reading frequency and on one of our two measures of receptive vocabulary. Moreover, we measured treatment impacts on this vocabulary measure at a 6-month follow-up and found that they were persistent. This light-touch intervention was particularly beneficial to male children, to children from families with low levels of education and from the most disadvantaged schools. Children from bilingual families benefited as much as their native counterparts. [ABSTRACT FROM AUTHOR]

Background: Considering multiple endpoints in clinical trials provide a more comprehensive understanding of treatment effects and may lead to increased power or reduced sample size, which may be beneficial in rare diseases. Besides the small sample sizes, allocation bias is an issue that affects the validity of these trials. We investigate the impact of allocation bias on testing decisions in clinical trials with multiple endpoints and offer a tool for selecting an appropriate randomization procedure (RP). Methods: We derive a model for quantifying the effect of allocation bias depending on the RP in the case of two-arm parallel group trials with continuous multiple endpoints. We focus on two approaches to analyze multiple endpoints, either the Šidák procedure to show efficacy in at least one endpoint and the all-or-none procedure to show efficacy in all endpoints. Results: To evaluate the impact of allocation bias on the test decision we propose a biasing policy for multiple endpoints. The impact of allocation on the test decision is measured by the family-wise error rate of the Šidák procedure and the type I error rate of the all-or-none procedure. Using the biasing policy we derive formulas to calculate these error rates. In simulations we show that, for the Šidák procedure as well as for the all-or-none procedure, allocation bias leads to inflation of the mean family-wise error and mean type I error, respectively. The strength of this inflation is affected by the choice of the RP. Conclusion: Allocation bias should be considered during the design phase of a trial to increase validity. The developed methodology is useful for selecting an appropriate RP for a clinical trial with multiple endpoints to minimize allocation bias effects. [ABSTRACT FROM AUTHOR]

Rational approximation is a powerful tool to obtain accurate surrogates for nonlinear functions that are easy to evaluate and linearize. The interpolatory adaptive Antoulas--Anderson (AAA) method is one approach to construct such approximants numerically. For large-scale vector-and matrix-valued functions, however, the direct application of the set-valued variant of AAA becomes inefficient. We propose and analyze a new sketching approach for such functions called sketchAAA that, with high probability, leads to much better approximants than previously suggested approaches while retaining efficiency. The sketching approach works in a black-box fashion where only evaluations of the nonlinear function at sampling points are needed. Numerical tests with nonlinear eigenvalue problems illustrate the efficacy of our approach, with speedups over 200 for sampling large-scale black-box functions without sacrificing accuracy. [ABSTRACT FROM AUTHOR]

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. Significance: 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. Trial Registration: ClinicalTrials.gov identifier: NCT03475225 (03‐22‐2018). [ABSTRACT FROM AUTHOR]

Functional neuroimaging analysis takes noisy multidimensional measurements as input and produces statistical inferences regarding the functional properties of brain regions as output. Such inferences are most commonly model-based, in that they assume a model of how neural activity translates to the measured signal (blood oxygenation level-dependent signal in the case of functional MRI). The use of models increases statistical sensitivity and makes it possible to ask fine-grained theoretical questions. However, this comes at the cost of making theoretical assumptions about the underlying data-generating process. An advantage of model-free approaches is that they can be used in cases where model assumptions are known not to hold. To this end, we introduce a randomization-based, model-free approach to functional neuroimaging. TWISTER randomization makes it possible to infer functional selectivity from correlations between experimental runs. We provide a proof of concept in the form of a visuomotor mapping experiment and discuss the possible strengths and limitations of this new approach in light of our empirical results. [ABSTRACT FROM AUTHOR]

Pairwise likelihood methods are commonly used for inference in parametric statistical models in cases where the full likelihood is too complex to be used, such as multivariate count data. Although pairwise likelihood methods represent a useful solution to perform inference for intractable likelihoods, several computational challenges remain. The pairwise likelihood function still requires the computation of a sum over all pairs of variables and all observations, which may be prohibitive in high dimensions. Moreover, it may be difficult to calculate confidence intervals of the resulting estimators, as they involve summing all pairs of pairs and all of the four-dimensional marginals. To alleviate these issues, we consider a randomized pairwise likelihood approach, where only summands randomly sampled across observations and pairs are used for the estimation. In addition to the usual tradeoff between statistical and computational efficiency, it is shown that, under a condition on the sampling parameter, this two-way random sampling mechanism makes the individual bivariate likelihood scores become asymptotically independent, allowing more computationally efficient confidence intervals to be constructed. The proposed approach is illustrated in tandem with copula-based models for multivariate count data in simulations, and in real data from a transcriptome study. for this article are available online. [ABSTRACT FROM AUTHOR]

This article describes the role of statistics in clinical trials, covering study design, directionality, variables, randomization and blinding, error reduction, probability and ethics as applied to trial design. [ABSTRACT FROM AUTHOR]

When a firm selects an assortment of products to offer to customers, it uses a choice model to anticipate their probability of purchasing each product. In practice, the estimation of these models is subject to statistical errors, which may lead to significantly suboptimal assortment decisions. In "Randomized Assortment Optimization," Wang, Peura, and Wiesemann show that the standard approach of deterministically selecting a single assortment to offer is not always optimal in this setting: Instead, the firm can do better by selecting an assortment randomly according to a prudently designed probability distribution. The authors show how an optimal randomization strategy can be determined for common choice models, improving performance in realistic data-driven settings. The results suggest that more general versions of the assortment optimization problem—incorporating business constraints, more flexible choice models and/or more general forms of uncertainty—tend to be more receptive to the benefits of randomization. When a firm selects an assortment of products to offer to customers, it uses a choice model to anticipate their probability of purchasing each product. In practice, the estimation of these models is subject to statistical errors, which may lead to significantly suboptimal assortment decisions. Recent work has addressed this issue using robust optimization, where the true parameter values are assumed unknown and the firm chooses an assortment that maximizes its worst-case expected revenues over an uncertainty set of likely parameter values, thus mitigating estimation errors. In this paper, we introduce the concept of randomization into the robust assortment optimization literature. We show that the standard approach of deterministically selecting a single assortment to offer is not always optimal in the robust assortment optimization problem. Instead, the firm can improve its worst-case expected revenues by selecting an assortment randomly according to a prudently designed probability distribution. We demonstrate this potential benefit of randomization both theoretically in an abstract problem formulation as well as empirically across three popular choice models: the multinomial logit model, the Markov chain model, and the preference ranking model. We show how an optimal randomization strategy can be determined exactly and heuristically. Besides the superior in-sample performance of randomized assortments, we demonstrate improved out-of-sample performance in a data-driven setting that combines estimation with optimization. Our results suggest that more general versions of the assortment optimization problem—incorporating business constraints, more flexible choice models and/or more general uncertainty sets—tend to be more receptive to the benefits of randomization. Funding: Z. Wang acknowledges funding from the Imperial College President's PhD Scholarship programme. W. Wiesemann acknowledges funding from the Engineering and Physical Sciences Research Council [Grants EP/R045518/1, EP/T024712/1, and EP/W003317/1]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/opre.2022.0129. [ABSTRACT FROM AUTHOR]

The article presents approaches to defining quality criteria for pedagogical experimental research. Particular attention is paid to the evidence-based approach in pedagogy. It is argued that pedagogical research today is an integral part of the educational process and dissertations on pedagogical sciences. However, it should be noted that there are problems with the quality of such studies, which constitute a significant share of the total number of defended dissertations, and this causes an urgent need to develop methodological principles and criteria for assessing their quality. But it is not every pedagogical research that is the subject of this paper: its focus is on the methodological foundations of experimental pedagogical research or simply experimental research in pedagogy, which often do not meet the requirements of the scientific method. The authors analyzed the main topics of pedagogical research in Russia and abroad. The key results and conclusions of the study are the complex requirements for dissertations as a scientific product and pedagogical research, which determine the algorithm for obtaining proven, reliable data used in science. It is concluded that experimental research in the field of pedagogy should be carried out in accordance with the requirements for all empirical research. In particular, special attention is paid to ethical issues of pedagogical research and procedures for implementing the experimental method.

This article provides an introduction to randomized response polling, a technique which was designed to allow for questioning on sensitive issues while protecting the respondent’s privacy and avoiding social desirability bias. It is described in terms that are suitable for presentation and use in any classroom environment. Instructions for plain users are included, along with the results of a small in-class implementation. The underpinnings of the method, which are laid out for the statistically savvy, illustrate the tradeoff between data acquisition and privacy protection. A few suitable references are also included for those who wish to dig further into the subject. Supplementary materials for this article are available online.

The classic framework of Anscombe and Aumann (Ann Math Stat 34:199–205, 1963) for decision-making under uncertainty postulates both a primary source of uncertainty (the "horse race") and an auxiliary randomization device (the "roulette wheel"). It also imposes a specific timing of resolution of uncertainty as the horse race takes place before the roulette is played. While this timing is without loss of generality for Subjective Expected Utility, it forbids plausible choice patterns of ambiguity aversion. In this paper, we reverse this timing by assuming that the roulette is played prior to the horse race and we obtain an axiomatic characterization of Choquet Expected Utility that is dual to that of Schmeidler (Econometrica 57(3):571–587, 1989). In this representation, ambiguity aversion is characterized by an aversion to conditioning roulette acts on horse events which, as we argue, is more plausible. Moreover, it can be larger than in Schmeidler's model. Finally, our reversed timing yields incentive compatibility of the random incentive mechanisms, frequently used in experiments for eliciting ambiguity attitudes. [ABSTRACT FROM AUTHOR]

Abstract 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. Conclusion 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.

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.

Abstract 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.

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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Low rank matrix approximations appear in a number of scientific computing applications. We consider the Nyström method for approximating a positive semidefinite matrix A. In the case that A is very large or its entries can only be accessed once, a single-pass version may be necessary. In this work, we perform a complete rounding error analysis of the single-pass Nyström method in two precisions, where the computation of the expensive matrix product with A is assumed to be performed in the lower of the two precisions. Our analysis gives insight into how the sketching matrix and shift should be chosen to ensure stability, implementation aspects which have been commented on in the literature but not yet rigorously justified. We further develop a heuristic to determine how to pick the lower precision, which confirms the general intuition that the lower the desired rank of the approximation, the lower the precision we can use without detriment. We also demonstrate that our mixed precision Nyström method can be used to inexpensively construct limited memory preconditioners for the conjugate gradient method and derive a bound the condition number of the resulting preconditioned coefficient matrix. We present numerical experiments on a set of matrices with various spectral decays and demonstrate the utility of our mixed precision approach. [ABSTRACT FROM AUTHOR]

There is a growing need to evaluate of multiple competing drugs in phase II trials where the number of patients is often limited, and simultaneous assessment of both efficacy and toxicity is crucial. To avoid the waste of research resources, it is indeed more efficient to screen multiple drugs at once in a platform phase II setting. We aim to adapt the Bayesian optimal phase II (BOP2) design to multi-arm trials for both uncontrolled and controlled settings. The binary efficacy and toxicity endpoints are modeled by a Dirichlet distribution as a vector of four outcomes. Posterior marginal distributions at each analysis are used to derive the monitoring threshold that varies during the trial. We control the family-wise Type I error rate for multiple comparison against a common reference value or a shared control. We conduct simulation studies under both uncontrolled and controlled settings to evaluate the operating characteristics of the proposed design. Our simulations demonstrate that the design exhibits better operating characteristics compared to a design using a constant threshold and is less sensitive to changes in accrual rate relative to what was planned. The design had promising operating characteristics and could be used in phase II oncology clinical trials for evaluating multiple drugs at a time. [ABSTRACT FROM AUTHOR]

We examine whether the way individuals randomize between options captures their decision confidence. In two experiments in which subjects faced pairs of options (a lottery and a varying sure payment), we allowed subjects to choose randomization probabilities according to which they would receive each option. Separately, we obtained two measures of self-reported confidence - confidence statements and probabilistic confidence - for choosing between the two options. Consistent with the predictions of two theoretical frameworks incorporating preference uncertainty, the randomization probabilities correlated strongly with both self-reported measures (median Spearman correlations between 0.86 to 0.89) and corresponded in absolute levels to probabilistic confidence. This relationship is robust to two exogenous manipulations of decision confidence, where we varied the complexity of the lottery and subjects' experience with the lottery. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Colombiana is the property of Acta Medica Colombiana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Background Older adults make up half of those with cancer and are prone to mood disorders, such as depression and severe anxiety, resulting in negative repercussions on their health-related quality-of-life (HRQOL). Educational interventions have been shown to reduce adverse psychological outcomes. We examined the effect of educational interventions on the severity of psychological outcomes in older adults with cancer (OAC) in the community. Method This PRISMA-adherent systematic review involved a search of PubMed, MedLine, Embase and PsycINFO for randomised controlled trials (RCTs) that evaluated educational interventions impacting the severity of depression, anxiety and HRQOL in OAC. Random effects meta-analyses and meta-regressions were used for the primary analysis. Results Fifteen RCTs were included. Meta-analyses showed a statistically insignificant decrease in the severity of depression (SMD = −0.30, 95%CI: −0.69; 0.09), anxiety (SMD = −0.30, 95%CI: −0.73; 0.13) and improvement in overall HRQOL scores (SMD = 0.44, 95%CI: −0.16; 1.04). However, subgroup analyses revealed that these interventions were particularly effective in reducing the severity of depression and anxiety in specific groups, such as OAC aged 60–65, those with early-stage cancer, those with lung cancer and those treated with chemotherapy. A systematic review found that having attained a higher education and income level increased the efficacy of interventions in decreasing the severity of adverse psychological outcomes. Conclusion Although overall meta-analyses were statistically insignificant, subgroup meta-analyses highlighted a few specific subgroups that the educational interventions were effective for. Future interventions can be implemented to target these vulnerable groups. [ABSTRACT FROM AUTHOR]

In today's highly digitized landscape, securing digital communication is paramount due to threats like hacking, unauthorized data access, and network policy violations. The response to these challenges has been the development of cryptography applications, though many existing techniques face issues of complexity, efficiency, and limitations. Notably, sophisticated intruders can easily discern encrypted data during transmission, casting doubt on overall security. In contrast to encryption, steganography offers the unique advantage of concealing data without easy detection, although it, too, grapples with challenges. The primary hurdles in image steganography revolve around the quality and payload capacity of the cover image, which are persistently compromised. This article introduces a pioneering approach that integrates image steganography and encryption, presenting the BitPatternStego method. This novel technique addresses prevalent issues in image steganography, such as stego-image quality and payload, by concealing secret data within image pixels with identical bit patterns as their characters. Consequently, concerns regarding the quality and payload capacity of steganographic images become obsolete. Moreover, the BitPatternStego method boasts the capability to generate millions of keys for the same secret message, offering a robust and versatile solution to the evolving landscape of digital security challenges. [ABSTRACT FROM AUTHOR]

Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials. Clinical Trials Registration. NCT04518410.

Abstract 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

Abstract Seasonal influenza is usually considered an acute respiratory infection with a full recovery within a week. In addition to the traditional outcomes, there is now evidence of indirect effects in terms of neurological and functional complications. Major organ systems can be affected, underlining the need for preventative measures against infection. The aim of this podcast, featuring Dr. Ann Falsey, Dr. Stefania Maggi, and Dr. Tor Biering-Sørensen, is to outline influenza complications beyond acute respiratory disease, as well as discussing the need for quality of evidence when evaluating influenza vaccines. Assessing the benefits of vaccination can be challenging. To ensure a high quality of evidence, the innovative randomization of patients within the study design to avoid bias and the assessment of additional outcomes beyond immunogenicity as well as the inclusion of a broad population—including frail or vulnerable individuals—are essential. Studies leveraging nationwide registries such as the DANFLU-2 trial in Denmark highlight the advantages of a digitalized healthcare system for conducting large-scale randomized trials. Furthermore, large-scale trials such as the Gravenstein study have supplied a sizable body of evidence supporting the use of high-dose influenza vaccine in older adults. In conclusion, achieving a high quality of evidence is key for decision-making on seasonal influenza vaccines.

The REVM method is a modernized option of classical EVM method. The new method has been developed for applying in unstable condition of works implementation. When the works can be accidentally disturbed and the impact of random disruption factors on course and results of works must be taken into consideration. Next, Randomized Budgeted Duration to Completion and Randomized Budgeted Cost to Completion that is duration and cost of works remaining to execution after each inspection, as well as the Randomized Budgeted Duration at Completion and Randomized Budgeted Cost at Completion that is duration and cost of all works of the project completion after the site inspection. Moreover, the risk of durations and costs overrun of works are evaluated. It is important that input data required for the REVM method are the similar and are measured in the same way as in typical control of advancement works. But results of the application consist new decision information. Control of the investment under deterministic conditions, without taking into account the risk of disruptions, resulted in a final deviation from the planned budget of over 7%, and from the planned completion of the investment by almost 12%. Without analysing the factor related to disruptions at the investment implementation stage, the material and financial schedule was completely outdated. On the other hand, when controlling the investment under risk conditions and introducing organizational and technological changes adequate to the inspection reports, the final deviation from the planned budget was less than 2%, and slightly more than 2% from the planned completion date. Researches confirm that the results received by using the REVM method well reflect real situation of works implementation.

A frequently addressed issue in clinical trials is the comparison of censored paired survival outcomes, for example, when individuals were matched based on their characteristics prior to the analysis. In this regard, a proper incorporation of the dependence structure of the paired censored outcomes is required and, up to now, appropriate methods are only rarely available in the literature. Moreover, existing methods are not motivated by the strive for insights by means of an easy‐to‐interpret parameter. Hence, we seek to develop a new estimand‐driven method to compare the effectiveness of two treatments in the context of right‐censored survival data with matched pairs. With the help of competing risks techniques, the so‐called relative treatment effect is estimated. This estimand describes the probability that individuals under Treatment 1 have a longer lifetime than comparable individuals under Treatment 2. We derive hypothesis tests and confidence intervals based on a studentized version of the estimator, where resampling‐based inference is established by means of a randomization method. In a simulation study, we demonstrate for numerous sample sizes and different amounts of censoring that the developed test exhibits a good power. Finally, we apply the methodology to a well‐known benchmark data set from a trial with patients suffering from diabetic retinopathy. [ABSTRACT FROM AUTHOR]

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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. Objective To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. Design Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. Results The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I 2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P  < 0.05 after Bonferroni correction). Conclusion Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy. [ABSTRACT FROM AUTHOR]

Background Emerging evidence suggests health-promoting properties of increased protein intake. There is increased interest in plant protein but a dearth of information in relation to its impact on muscle function. The objective of the present work was to examine the impact of intake of different types of proteins on muscle functional parameters including handgrip strength, biomarkers of metabolic health, sleep quality and quality of life in a group of older adults. Methods Healthy men and women aged 50 years and older entered a double-blinded, randomised, controlled nutritional intervention study with three parallel arms: high plant protein, high dairy protein and low protein. Participants consumed once daily a ready-to-mix shake (containing 20 g of protein in high protein groups) for 12 weeks. Changes in handgrip and leg strength, body composition, metabolic health, quality of life and sleep quality were analysed by linear mixed models in an intention-to-treat approach. Results Eligible participants (n  = 171) were randomly assigned to the groups (plant: n  = 60, dairy: n  = 56, low protein: n  = 55) and 141 completed the study. Handgrip strength increased after the intervention (P time = 0.038), with no significant difference between the groups. There was no significant difference between groups for any other health outcomes. Conclusions In a population of older adults, increasing protein intake by 20 g daily for 12 weeks (whether plant-based or dairy-based) did not result in significant differences in muscle function, body composition, metabolic health, sleep quality or quality of life, compared with the low protein group. [ABSTRACT FROM AUTHOR]

Introduction Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology. Method We developed our typology by qualitatively synthesising community-based complex interventions to sustain independence in older people, evaluated in randomised controlled trials (RCTs), in four stages: (i) systematically identifying relevant RCTs; (ii) extracting descriptions of interventions (including control) using the Template for Intervention Description and Replication; (iii) generating categories of key intervention features and (iv) grouping the interventions based on these categories. PROSPERO registration: CRD42019162195. Results Our search identified 129 RCTs involving 266 intervention arms. The Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology comprises 14 action components and 5 tailoring components. Action components include procedures for treating patients or otherwise intended to directly improve their outcomes; regular examples include formal homecare; physical exercise; health education; activities of daily living training; providing aids and adaptations and nutritional support. Tailoring components involve a process that may result in care planning, with multiple action components being planned, recommended or prescribed. Multifactorial action from care planning was the most common tailoring component. It involves individualised, multidomain assessment and management, as in comprehensive geriatric assessment. Sixty-three different intervention types (combinations) were identified. Conclusions Our typology provides an empirical basis for service planning and evidence synthesis. We recommend better reporting about organisational aspects of interventions and usual care. [ABSTRACT FROM AUTHOR]

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P  = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P  = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P  = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this. [ABSTRACT FROM AUTHOR]

Introduction This process evaluation was conducted in parallel to the randomised controlled feasibility trial of NIDUS-Professional, a manualised remote dementia training intervention for homecare workers (HCWs), delivered alongside an individualised intervention for clients living with dementia and their family carers (NIDUS-Family). The process evaluation reports on: (i) intervention reach, dose and fidelity; (ii) contexts influencing agency engagement and (iii) alignment of findings with theoretical assumptions about how the intervention might produce change. Methods We report proportions of eligible HCWs receiving any intervention (reach), number of sessions attended (dose; attending ≥4/6 main sessions was predefined as adhering), intervention fidelity and adherence of clients and carers to NIDUS-Family (attending all 6–8 planned sessions). We interviewed HCWs, managers, family carers and facilitators. We integrated and thematically analysed, at the homecare agency level, qualitative interview and intervention recording data. Results 32/141 (23%) of eligible HCWs and 7/42 (17%) of family carers received any intervention; most who did adhered to the intervention (89% and 71%). Intervention fidelity was high. We analysed interviews with 20/44 HCWs, 3/4 managers and 3/7 family carers, as well as intervention recordings involving 32/44 HCWs. All agencies reported structural challenges in supporting intervention delivery. Agencies with greater management buy-in had higher dose and reach. HCWs valued NIDUS-Professional for enabling group reflection and peer support, providing practical, actionable care strategies and increasing their confidence as practitioners. Conclusion NIDUS-Professional was valued by HCWs. Agency management, culture and priorities were key barriers to implementation; we discuss how to address these in a future trial. [ABSTRACT FROM AUTHOR]

Background Patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are underrepresented in specialist palliative home care (SPHC). However, the complexity of their conditions requires collaboration between general practitioners (GPs) and SPHC teams and timely integration into SPHC to effectively meet their needs. Objective To facilitate joint palliative care planning and the timely transfer of patients with advanced chronic non-malignant conditions to SPHC. Methods A two-arm, unblinded, cluster-randomised controlled trial. 49 GP practices in northern Germany were randomised using web-based block randomisation. We included patients with advanced CHF, COPD and/or dementia. The KOPAL intervention consisted of a SPHC nurse–patient consultation followed by an interprofessional telephone case conference between SPHC team and GP. The primary outcome was the number of hospital admissions 48 weeks after baseline. Secondary analyses examined the effects on health-related quality of life and self-rated health status, as measured by the EuroQol 5D scale. Results A total of 172 patients were included in the analyses. 80.4% of GP practices had worked with SHPC before, most of them exclusively for cancer patients. At baseline, patients reported a mean EQ-VAS of 48.4, a mean quality of life index (EQ-5D-5L) of 0.63 and an average of 0.80 hospital admissions in the previous year. The intervention did not significantly reduce hospital admissions (incidence rate ratio = 0.79, 95%CI: [0.49, 1.26], P  = 0.31) or the number of days spent in hospital (incidence rate ratio = 0.65, 95%CI: [0.28, 1.49], P  = 0.29). There was also no significant effect on quality of life (∆ = −0.02, 95%CI: [−0.09, 0.05], P  = 0.53) or self-rated health (∆ = −2.48, 95%CI: [−9.95, 4.99], P  = 0.51). Conclusions The study did not show the hypothesised effect on hospitalisations and health-related quality of life. Future research should focus on refining this approach, with particular emphasis on optimising the timing of case conferences and implementing discussed changes to treatment plans, to improve collaboration between GPs and SPHC teams. [ABSTRACT FROM AUTHOR]