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Purpose Methods Results Conclusion The purpose of this study is to investigate 3‐year efficacy of orthokeratology lenses (OKL) in controlling axial length progression in myopic Scandinavian children. Through a cross‐over design of the control group to compare the treatment efficacy in younger versus older children, with the latter having higher cycloplegic spherical refractive error (cSEQ) at treatment initiation. Further, the study aimed to evaluate the safety of the treatment.This was a continuation of the randomized controlled study Clinical study Of Near‐sightedness; TReatment with Orthokeratology Lenses (CONTROL study) in which the follow‐up period of the original intervention group, that received OKL, was extended from 18 months to 36 months. Meanwhile, the original control group was crossed‐over to OKL after the 18‐month follow‐up visit and treated for 18 months. Biometry was measured using Lenstar LS900, and contact lens complications were graded according to Efron Grading Scale for Contact Lens Complications (Efron score). Mixed models were used for statistical analysis.Nineteen subjects in the OKL group and 28 in the control group completed the CONTROL study. Hereof, 17 and 24 subjects from the OKL group and control group, respectively, agreed to participate in the CONTROL2 study. In the OKL continue group, the treatment efficacy did not decline during the 3‐year study period (p‐values for follow‐up visits were all ≥0.82). There was no statistically significant difference between treatment efficacy when OKL treatment was initiated in younger versus older children (p‐value ≥0.14 for all follow‐up visits). Low‐grade corneal staining was seen in several subjects at some point during the study, but here were no treatment‐requiring or sight‐threatening adverse events during the study period.The efficacy of myopia control by OKL was stable during 3 years of treatment. Similar treatment efficacies were found regardless of the age at treatment initiation. No severe adverse events occurred during the study period. [ABSTRACT FROM AUTHOR]

The Break4Brain project aims to elucidate the effects of both acute and chronic physical activity (PA) on educational achievement in children with and without Attention Deficit Hyperactivity Disorder (ADHD). This study will be conducted in two phases: a cross-over design followed by a hybrid type 1 implementation-effectiveness trial, which includes both a cluster randomized controlled trial (RCT) and a qualitative study. In phase I, 60 children aged 10–12, with 30 each from ADHD and non-ADHD groups, will participate in a laboratory-based study over 4 days within 1 month. They will participate in three counterbalanced experimental conditions: (i) PA with cognitive engagement, (ii) PA without cognitive engagement, and (iii) a cognitively engaging control. This phase will assess acute changes in brain function, academic performance, working memory, inhibitory control, and sustained attention. Phase II will involve 600 children aged 10–12, randomly assigned to either a video-based PA program or a control group (300 children per group) in an 8-week cluster RCT. This phase will also incorporate a qualitative approach to explore the implementation context through pre- and post-intervention semi-structured interviews with teachers and school staff, and questionnaires for students. The outcomes of interest in this phase will include working memory, cognitive flexibility, selective attention, and academic performance. For the cross-over study, we hypothesize that PA conditions will enhance the studied outcomes compared to the control condition. In the RCT, we anticipate that the 8-week active breaks program will result in significant improvements in the selected outcomes compared to the control group. This study is expected to make pioneering contributions by including novel variables and focusing on the ADHD population. Furthermore, if the cluster RCT proves effective, it could offer a practical and cost-effective resource for integrating active breaks into daily school routines.

BackgroundSuboptimal treatment upon progression may affect overall survival (OS) results in oncology randomized controlled trials (RCTs). We aim to assess the proportion of trials reporting post-progression treatment.MethodsThis cross-sectional analysis included two concurrent analyses. The first one examined all published RCTs of anti-cancer drugs in six high impact medical/oncology journals between January 2018 and December 2020. The second studied all US Food and Drug Administration (FDA) approved anti-cancer drugs during the same period. Included trials needed to study an anti-cancer drug in the advanced or metastatic setting. Data abstracted included the tumor type, characteristics of trials, and reporting and assessment of post-progression treatment.ResultsThere were 275 published trials and 77 US FDA registration trials meeting inclusion criteria. Assessable post-progression data were reported in 100/275 publications (36.4%) and 37/77 approvals (48.1%). Treatment was considered substandard in 55 publications (n = 55/100, 55.0%) and 28 approvals (n = 28/37, 75.7%). Among trials with assessable post-progression data and positive OS results, a subgroup analysis identified substandard post-progression treatment in 29 publications (n = 29/42, 69.0%) and 20 approvals (n = 20/26, 76.9%). Overall, 16.4% of publications (45/275) and 11.7% of registration trials (9/77) had available post-progression data assessed as appropriate.ConclusionWe found that most anti-cancer RCTs do not report assessable post-progression treatment. When reported, post-progression treatment was substandard in most trials. In trials reporting positive OS results and with assessable post-progression data, the proportion of trials with subpar post-progression treatment was even higher. Discrepancies between post-progression therapy in trials and the standard of care can limit RCT results' applicability. Regulatory rules should enforce higher requirements regarding post-progression treatment access and reporting.

Fine-scale meiotic recombination is fundamental to the outcome of natural and artificial selection. Here, dense genetic mapping and haplotype reconstruction were used to estimate recombination for a full factorial Populus trichocarpa cross of 7 males and 7 females. Genomes of the resulting 49 full-sib families (N = 829 offspring) were resequenced, and high-fidelity biallelic SNP/INDELs and pedigree information were used to ascertain allelic phase and impute progeny genotypes to recover gametic haplotypes. The 14 parental genetic maps contained 1,820 SNP/INDELs on average that covered 376.7 Mb of physical length across 19 chromosomes. Comparison of parental and progeny haplotypes allowed fine-scale demarcation of cross-over regions, where 38,846 cross-over events in 1,658 gametes were observed. Cross-over events were positively associated with gene density and negatively associated with GC content and long-terminal repeats. One of the most striking findings was higher rates of cross-overs in males in 8 out of 19 chromosomes. Regions with elevated male cross-over rates had lower gene density and GC content than windows showing no sex bias. High-resolution analysis identified 67 candidate cross-over hotspots spread throughout the genome. DNA sequence motifs enriched in these regions showed striking similarity to those of maize, Arabidopsis, and wheat. These findings, and recombination estimates, will be useful for ongoing efforts to accelerate domestication of this and other biomass feedstocks, as well as future studies investigating broader questions related to evolutionary history, perennial development, phenology, wood formation, vegetative propagation, and dioecy that cannot be studied using annual plant model systems.

Abstract.Experimenters have limited flexibility in their choice of cross-over designs, in terms of, number of treatments, subjects, and repeated measurements. Also, cross-over design balanced with higher-order carryover effects presented in the literature requires a large number of experimental subjects, which is impractical for its implementation. Most experimental studies demand a smaller number of subjects, which is possible only in a minimally balanced cross-over design. In this article, two simple methods have been presented, which construct minimal balanced cross-over designs having less, equal, and more periods than the number of treatments. The first method constructs cross-over designs with more periods, while the second method constructs cross-over designs with less or equal periods. As a result, four new families of cross-over designs have been obtained, in which one family of cross-over designs has periods greater than the number of treatments, two families of cross-over designs have three periods, and one family of cross-over designs has periods equal to the number of treatments. All the designs possess good efficiency of separability, and therefore they are suitable for the estimation of treatments and first-second carryover effects of treatments at lower cost of experiments due to a smaller number of experimental subjects as compared to the designs available in the literature. [ABSTRACT FROM AUTHOR]

BackgroundThe World Health Organization (WHO) and the Food and Agriculture Organization (FAO) recommend the consumption of less than 2,000 mg of sodium/day to reduce blood pressure and the risk of conditions such as cardiovascular disease and coronary heart disease. The sodium intake among Vietnamese was reported to be 7,200 mg/d or more. Free L-glutamate enhances flavor when it is added to food and improves the taste of sodium-reduced foods.ObjectiveThis study aims to investigate whether the intake of free L-glutamate-rich seasonings contributes to maintaining a low sodium intake in a cross-over study.MethodsFrom a total of 145 subjects, 42 participants were screened for participation in the cross-over design study. Subjects were randomly allocated to the Low free L-glutamate group (Low free L-Gl) and the Normal free L-glutamate group (Normal free L-Gl). Both received a direct educational guideline to reduce sodium intake. The Low free L-Gl group started with a restriction in the variety of free L-glutamate-rich seasonings, and the Normal free L-Gl group had no restriction in the variety of seasonings. Blood pressure was measured at week 0 (baseline), week 2, week 4, and week 6, while body weight, height, urine sodium and potassium excretion, chromogranin-A (CgA pmol/mg protein) from saliva, and free L-glutamate from food were measured at week 0, week 3, and week 6.ResultsIn Low free L-Gl, the amount of free L-glutamate in food decreased significantly from baseline to week 6 (p 0.05). However, the reduction of sodium excretion at week 6 was 22% in Low free L-Gl (5,875 mg/d vs. 4,603 mg/d, p

This article discusses a study that aimed to determine whether moderate blood volume expansion (BVexp) can increase cardiac capacity and aerobic capacity in both men and women. The study found that BVexp resulted in increased resting heart rate and left ventricular cardiac output in both sexes. However, it also led to a decrease in pulmonary oxygen uptake during exercise, indicating that expanding blood volume alone may not lead to functional improvements in aerobic capacity. The study suggests that additional adaptations to endurance training and/or hypervolemia may be necessary for enhancing circulatory and aerobic capacities. [Extracted from the article]

Abstract Background Recommendations for statistical methods in rare disease trials are scarce, especially for cross-over designs. As a result various state-of-the-art methodologies were compared as neutrally as possible using an illustrative data set from epidermolysis bullosa research to build recommendations for count, binary, and ordinal outcome variables. For this purpose, parametric (model averaging), semiparametric (generalized estimating equations type [GEE-like]) and nonparametric (generalized pairwise comparisons [GPC] and a marginal model implemented in the R package nparLD) methods were chosen by an international consortium of statisticians. Results It was found that there is no uniformly best method for the aforementioned types of outcome variables, but in particular situations, there are methods that perform better than others. Especially if maximizing power is the primary goal, the prioritized unmatched GPC method was able to achieve particularly good results, besides being appropriate for prioritizing clinically relevant time points. Model averaging led to favorable results in some scenarios especially within the binary outcome setting and, like the GEE-like semiparametric method, also allows for considering period and carry-over effects properly. Inference based on the nonparametric marginal model was able to achieve high power, especially in the ordinal outcome scenario, despite small sample sizes due to separate testing of treatment periods, and is suitable when longitudinal and interaction effects have to be considered. Conclusion Overall, a balance has to be found between achieving high power, accounting for cross-over, period, or carry-over effects, and prioritizing clinically relevant time points.

The objective of the study was to explore the impact of leaders’ ages and followers’ perceptions of organizational justice (POJ) on the transfer of psychological capital (PsyCap) from leaders to followers, particularly examining how employees’ resilience is influenced by leaders’ PsyCap. While some evidence exists regarding PsyCap’s trickle-down effect, the specific circumstances triggering this phenomenon remain unclear. This study investigates the relationship between followers’ and leaders’ PsyCap, employing the Social Cognitive Theory and considering the moderating effects of leaders’ age and POJ. The study focused on leader-follower dyads within a randomly selected sample of 406 businesses, encompassing 812 respondents. The survey investigation utilized the CAPI approach. The hypothesized model underwent testing through multilevel dyadic regression analysis, employing an actorpartner interdependence model. The findings support two moderators — employees’ POJ and managers’ age — and highlight the cross-over effect of PsyCap. Specifically, a stronger trickle-down link is observed when a leader is older and operating within a low POJ environment. Additionally, the study revealed a positive correlation between employees’ PsyCap and POJ. The development of POJ enhances employees’ PsyCap and resilience, while leaders’ PsyCap may compensate for organizational POJ deficiencies. This study is among the first to explore PsyCap’s moderators, specifically analyzing leaders’ ages and POJ as factors influencing the cross-over effect of PsyCap. By identifying previously unrecognized moderators affecting the cross-over PsyCap effect, this research contributes significantly to the PsyCap literature. [ABSTRACT FROM AUTHOR]

Background: Recommendations for statistical methods in rare disease trials are scarce, especially for cross-over designs. As a result various state-of-the-art methodologies were compared as neutrally as possible using an illustrative data set from epidermolysis bullosa research to build recommendations for count, binary, and ordinal outcome variables. For this purpose, parametric (model averaging), semiparametric (generalized estimating equations type [GEE-like]) and nonparametric (generalized pairwise comparisons [GPC] and a marginal model implemented in the R package nparLD) methods were chosen by an international consortium of statisticians. Results: It was found that there is no uniformly best method for the aforementioned types of outcome variables, but in particular situations, there are methods that perform better than others. Especially if maximizing power is the primary goal, the prioritized unmatched GPC method was able to achieve particularly good results, besides being appropriate for prioritizing clinically relevant time points. Model averaging led to favorable results in some scenarios especially within the binary outcome setting and, like the GEE-like semiparametric method, also allows for considering period and carry-over effects properly. Inference based on the nonparametric marginal model was able to achieve high power, especially in the ordinal outcome scenario, despite small sample sizes due to separate testing of treatment periods, and is suitable when longitudinal and interaction effects have to be considered. Conclusion: Overall, a balance has to be found between achieving high power, accounting for cross-over, period, or carry-over effects, and prioritizing clinically relevant time points. [ABSTRACT FROM AUTHOR]

To optimize the use of data from a small number of subjects in rare disease trials, an at first sight advantageous design is the repeated measures cross‐over design. However, it is unclear how these within‐treatment period and within‐subject clustered data are best analyzed in small‐sample trials. In a real‐data simulation study based upon a recent epidermolysis bullosa simplex trial using this design, we compare non‐parametric marginal models, generalized pairwise comparison models, GEE‐type models and parametric model averaging for both repeated binary and count data. The recommendation of which methodology to use in rare disease trials with a repeated measures cross‐over design depends on the type of outcome and the number of time points the treatment has an effect on. The non‐parametric marginal model testing the treatment–time‐interaction effect is suitable for detecting between group differences in the shapes of the longitudinal profiles. For binary outcomes with the treatment effect on a single time point, the parametric model averaging method is recommended, while in the other cases the unmatched generalized pairwise comparison methodology is recommended. Both provide an easily interpretable effect size measure, and do not require exclusion of periods or subjects due to incompleteness. [ABSTRACT FROM AUTHOR]

Abstract Background Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. Methods STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (“cluster”) has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT’s current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. Discussion The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. Trial registration ISRCTN: 10412338. Registration date: October 24, 2019.

The objective of the study was to explore the impact of leaders’ ages and followers’ perceptions of organizational justice (POJ) on the transfer of psychological capital (PsyCap) from leaders to followers, particularly examining how employees’ resilience is influenced by leaders’ PsyCap. While some evidence exists regarding PsyCap’s trickle-down effect, the specific circumstances triggering this phenomenon remain unclear. This study investigates the relationship between followers’ and leaders’ PsyCap, employing the Social Cognitive Theory and considering the moderating effects of leaders’ age and POJ. The study focused on leader-follower dyads within a randomly selected sample of 406 businesses, encompassing 812 respondents. The survey investigation utilized the CAPI approach. The hypothesized model underwent testing through multilevel dyadic regression analysis, employing an actor-partner interdependence model. The findings support two moderators —employees’ POJ and managers’ age — and highlight the cross-over effect of PsyCap. Specifically, a stronger trickle-down link is observed when a leader is older and operating within a low POJ environment. Additionally, the study revealed a positive correlation between employees’ PsyCap and POJ. The development of POJ enhances employees’ PsyCap and resilience, while leaders’ PsyCap may compensate for organizational POJ deficiencies. This study is among the first to explore PsyCap’s moderators, specifically analyzing leaders’ ages and POJ as factors influencing the cross-over effect of PsyCap. By identifying previously unrecognized moderators affecting the cross-over PsyCap effect, this research contributes significantly to the PsyCap literature.

Background: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. Methods: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. Discussion: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. Trial registration: ISRCTN: 10412338. Registration date: October 24, 2019. [ABSTRACT FROM AUTHOR]

Abstract Introduction Spondyloarthritis (SpA) is a serious chronic inflammatory rheumatism implying different painful and crippling symptoms that require a multidisciplinary approach for the patient. Fatigue is one of the less well treated symptoms, even if its repercussion on everyday life is noticeable. Shiatsu is a Japanese preventive and well-being therapy that aims to promote better health. However, the effectiveness of shiatsu in SpA-associated fatigue has never been studied yet in a randomized study. Methods and Analysis We describe the design of SFASPA (Etude pilote randomisée en cross-over évaluant l’efficacité du Shiatsu sur la FAtigue des patients atteints de SPondyloarthrite Axiale), a single-center, randomized controlled cross-over trial with allocation of patients according to a ratio (1:1) evaluating the effectiveness of shiatsu in SpA-associated fatigue. The sponsor is the Regional Hospital of Orleans, France. The two groups of 60 patients each will receive three “active” shiatsu and three sham shiatsu treatments (120 patients, 720 shiatsu). The wash-out period between the active and the sham shiatsu treatments is 4 months. Planned Outcomes The primary outcome is the percentage of patients responding to the FACIT-fatigue score. A response to fatigue is defined as an improvement, i.e., an increase of ≥ 4 points in the FACIT-fatigue score, which corresponds to the “minimum clinically important difference” (MCID). Differences in the evolution of activity and impact of the SpA will be assessed on several secondary outcomes. An important aim of this study is also to gather material for further trials with higher proof of evidence. Trial Registration NCT05433168, date of registration, June 21st, 2022 (clinicaltrials.gov).

Abstract Background Suboptimal treatment upon progression may affect overall survival (OS) results in oncology randomized controlled trials (RCTs). We aim to assess the proportion of trials reporting post-progression treatment. Methods This cross-sectional analysis included two concurrent analyses. The first one examined all published RCTs of anti-cancer drugs in six high impact medical/oncology journals between January 2018 and December 2020. The second studied all US Food and Drug Administration (FDA) approved anti-cancer drugs during the same period. Included trials needed to study an anti-cancer drug in the advanced or metastatic setting. Data abstracted included the tumor type, characteristics of trials, and reporting and assessment of post-progression treatment. Results There were 275 published trials and 77 US FDA registration trials meeting inclusion criteria. Assessable post-progression data were reported in 100/275 publications (36.4%) and 37/77 approvals (48.1%). Treatment was considered substandard in 55 publications (n = 55/100, 55.0%) and 28 approvals (n = 28/37, 75.7%). Among trials with assessable post-progression data and positive OS results, a subgroup analysis identified substandard post-progression treatment in 29 publications (n = 29/42, 69.0%) and 20 approvals (n = 20/26, 76.9%). Overall, 16.4% of publications (45/275) and 11.7% of registration trials (9/77) had available post-progression data assessed as appropriate. Conclusion We found that most anti-cancer RCTs do not report assessable post-progression treatment. When reported, post-progression treatment was substandard in most trials. In trials reporting positive OS results and with assessable post-progression data, the proportion of trials with subpar post-progression treatment was even higher. Discrepancies between post-progression therapy in trials and the standard of care can limit RCT results’ applicability. Regulatory rules should enforce higher requirements regarding post-progression treatment access and reporting.

Introduction: Spondyloarthritis (SpA) is a serious chronic inflammatory rheumatism implying different painful and crippling symptoms that require a multidisciplinary approach for the patient. Fatigue is one of the less well treated symptoms, even if its repercussion on everyday life is noticeable. Shiatsu is a Japanese preventive and well-being therapy that aims to promote better health. However, the effectiveness of shiatsu in SpA-associated fatigue has never been studied yet in a randomized study. Methods and Analysis: We describe the design of SFASPA (Etude pilote randomisée en cross-over évaluant l'efficacité du Shiatsu sur la FAtigue des patients atteints de SPondyloarthrite Axiale), a single-center, randomized controlled cross-over trial with allocation of patients according to a ratio (1:1) evaluating the effectiveness of shiatsu in SpA-associated fatigue. The sponsor is the Regional Hospital of Orleans, France. The two groups of 60 patients each will receive three "active" shiatsu and three sham shiatsu treatments (120 patients, 720 shiatsu). The wash-out period between the active and the sham shiatsu treatments is 4 months. Planned Outcomes: The primary outcome is the percentage of patients responding to the FACIT-fatigue score. A response to fatigue is defined as an improvement, i.e., an increase of ≥ 4 points in the FACIT-fatigue score, which corresponds to the "minimum clinically important difference" (MCID). Differences in the evolution of activity and impact of the SpA will be assessed on several secondary outcomes. An important aim of this study is also to gather material for further trials with higher proof of evidence. Trial Registration: NCT05433168, date of registration, June 21st, 2022 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Polypharmacy is becoming increasingly prevalent in society. Patients with polypharmacy are at greater risk for drug-drug interactions, which can influence the efficacy of treatment. Especially, in oncology this is a concern since neoplasms are increasing prevalent with age, as well as polypharmacy is. Besides drug-drug interactions, also herb-drug and food-drug interactions could be present. Knowledge of these interactions is of great importance for safe and effective anti-cancer treatment, because the therapeutic window of most of these oncologic drugs are small. To study pharmacokinetic interaction effects, a cross-over pharmacokinetic study is a widely used, efficient and scientifically robust design. Yet, several aspects need to be considered when carrying out an interaction study. This includes the knowledge of the advantages and disadvantages of a cross-over design. Furthermore, determination of the end point and research question of interest, calculation of the required sample size, analysis of the generated data with a robust statistical plan and consideration of the logtransformation for some pharmacokinetic parameters are important aspects to consider. Even though some guidelines exist regarding these key issues, no clear overview exists. In this article an overview of these aspects is provided and their effect is discussed.

Background/objectives: Around 11,500 artificial eyes are required yearly for new and existing patients. Artificial eyes have been manufactured and hand-painted at the National Artificial Eye Service (NAES) since 1948, in conjunction with approximately 30 local artificial eye services throughout the country. With the current scale of demand, services are under significant pressure. Manufacturing delays as well as necessary repainting to obtain adequate colour matching, may severely impact a patient’s rehabilitation pathway to a normal home, social and work life. However, advances in technology mean alternatives are now possible. The aim of this study is to establish the feasibility of conducting a large-scale study of the effectiveness and cost-effectiveness of digitally printed artificial eyes compared to hand-painted eyes. Methods: A cross-over, randomised feasibility study evaluating a digitally-printed artificial eye with a hand-painted eye, in patients aged ≥18 years with a current artificial eye. Participants will be identified in clinic, via ophthalmology clinic databases and two charity websites. Qualitative interviews will be conducted in the later phases of the study and focus on opinions on trial procedures, the different artificial eyes, delivery times, and patient satisfaction. Discussion: Findings will inform the feasibility, and design, of a larger fully powered randomised controlled trial. The long-term aim is to create a more life-like artificial eye in order to improve patients’ initial rehabilitation pathway, long term quality of life, and service experience. This will allow the transition of research findings into benefit to patients locally in the short term and National Health Service wide in the medium to long term. ISRCTN registration: ISRCTN85921622 (prospectively registered on 17/06/2021)

Fixing the genomic composition and multiplication through true potato seed (TPS) is an important challenge in autotetraploid potato. Disrupted meiotic cDNA (DMC1) is a meiotic gene that plays a central role in DNA recombination through crossing over in meiosis. Using the Arabidopsis DMC1 (AtDMC1) gene sequence, we retrieved Solanum tuberosum DMC1(StDMC1) from the diploid potato genome, and subsequently, sense and antisense regions of the StDMC1 gene were amplified in potato cv. Kufri Jyoti. The sense and antisense fragments were confirmed by Sanger-sequencing and cloned in the pRI101 vector. Agrobacterium-mediated transformation of the RNAi construct resulted in 44% transformation efficiency, and a total of 137 mutant lines were obtained. These mutant lines were further validated through pollen viability testing, and selected lines were used for gene expression analysis. The acetocarmine-based pollen staining showed reduced pollen viability ranging from 14 to 21% in four DMC1 mutant lines (DMC4-37, DMC4-41, DMC6-20, and DMC6-21), as compared to the Kufri Jyoti control plants, which on average exhibited 78% pollen viability. The phenotypic data was supported by the reduced expression of the StDMC1 gene in these four mutant lines compared to the control Kufri Jyoti. The results confirmed the generation of StDMC1 knockdown lines. This is the first report of StDMC1 mutant line generation in tetraploid potatoes and will be a step forward in generating non-recombinant mutants through sexual reproduction in potatoes. [ABSTRACT FROM AUTHOR]

Background and aims: Reducing alcohol consumption across populations would decrease the risk of a range of diseases, including many cancers, cardiovascular disease and Type 2 diabetes. The aim of the current study was to estimate the impact of using smaller bottles (37.5‐ versus 75‐cl) and glasses (290 versus 370 ml) on consuming wine at home. Design: Randomized controlled trial of households with cross‐over randomization to bottle size and parallel randomization to glass size. Setting: UK households. Participants: A total of 260 households consuming at least two 75‐cl bottles of wine each week, recruited from the general population through a research agency. The majority consisted of adults who were white and of higher socio‐economic position. Intervention: Households were randomized to the order in which they purchased wine in 37.5‐ or 75‐cl bottles, to consume during two 14‐day intervention periods, and further randomized to receive smaller (290 ml) or larger (350 ml) glasses to use during both intervention periods. Measurements Volume (ml) of study wine consumed at the end of each 14‐day intervention period, measured using photographs of purchased bottles, weighed on study scales. Findings Of the randomized households, 217 of 260 (83%) completed the study as per protocol and were included in the primary analysis. There was weak evidence that smaller bottles reduced consumption: after accounting for pre‐specified covariates, households consumed on average 145.7 ml (3.6%) less wine when drinking from smaller bottles than from larger bottles [95% confidence intervals (CI) = –335.5 to 43. ml; −8.3 to 1.1%; P = 0.137; Bayes factor (BF) = 2.00]. The evidence for the effect of smaller glasses was stronger: households consumed on average 253.3 ml (6.5%) less wine when drinking from smaller glasses than from larger glasses (95% CI = –517 to 10 ml; −13.2 to 0.3%; P = 0.065; BF = 2.96). Conclusions: Using smaller glasses to drink wine at home may reduce consumption. Greater uncertainty remains around the possible effect of drinking from smaller bottles. [ABSTRACT FROM AUTHOR]

The Surface Water and Ocean Topography (SWOT) mission will be affected by various sources of systematic errors, which are correlated in space and in time. Their amplitude before calibration might be as large as tens of centimeters, i.e., able to dominate the mission error budget. To reduce their magnitude, we developed so-called data-driven (or empirical) calibration algorithms. This paper provided a summary of the overall problem, and then presented the calibration framework used for SWOT, as well as the pre-launch performance simulations. We presented two complete algorithm sequences that use ocean measurements to calibrate KaRIN globally. The simple and robust Level-2 algorithm was implemented in the ground segment to control the main source of error of SWOT's hydrology products. In contrast, the more sophisticated Level-3 (multi-mission) algorithm was developed to improve the accuracy of ocean products, as well as the one-day orbit of the SWOT mission. The Level-2 algorithm yielded a mean inland error of 3–6 cm, i.e., a margin of 25–80% (of the signal variance) with respect to the error budget requirements. The Level-3 algorithm yielded ocean residuals of 1 cm, i.e., a variance reduction of 60–80% with respect to the Level-2 algorithm. [ABSTRACT FROM AUTHOR]

Cancelable biometric recognition techniques play a vital role in the privacy and security of remote surveillance systems to keep the genuine users’ confidential data safe and away from intruders. This research work presents an efficient cancelable biometric recognition framework that exploits an irreversible hybrid encryption algorithm. It incorporates Deoxyribonucleic, Ribonucleic Acid sequence (DNA and RNA) encryption technique, and an evolutionary optimization technique, namely Genetic Algorithms (GAs). These techniques are employed to create completely deformed templates from their original ones. Hence, the main contribution is introducing a novel biometric security framework that achieves unique randomness characteristics using RNA and DNA sequences and the evolutionary GA technique. The proposed framework produces entirely deformed biometric templates by ciphering the main discriminative features of the biometric traits of the authorized clients. It is firstly initialized by creating several encrypted biometric images for the original users with the logistic map. After that, the initially encrypted images are transformed into vectors of a binary array. Then, they are converted to their corresponding introns, and exons, and consequently, their relevant codons are stored in the cloud database. These relevant codons are replaced by new ones after generating encrypted RNA lists. The utilized encryption key for each template is extracted from the original biometric image through excessive permutations between pixels. The GA optimization technique is applied to select the most convenient biometric features. Finally, after employing the GA-based cross-over and mutation operations, the chosen features are used to generate the cancelable biometric traits. To assess the proposed framework, six different biometric databases are considered. These databases are Olivetti Research Laboratory (ORL) Faces (gray), CASIA v.5 Faces (color), UPOL Iris (gray), Indian Institute of Technology Delhi (IIT Delhi) Ear (color and gray), Fingerprint, and CASIA Palmprint (color and gray). The security performance of the proposed encryption algorithm is compared to those of recent studies in this field, such as Optical Scanning Holography (OSH) and Double Random Phase Encoding (DRPE). The simulation results prove the superior performance of the proposed framework in terms of all adopted evaluation metrics. The proposed framework provides high Area under the Receiver Operating Characteristic (AROC) curve that reaches 0.9990, low False Acceptance Rate (FAR) of 0.0015, more uniform histograms, high correlation values for genuine users, and completely hidden biometric features. In addition, from the security perspective, the proposed framework achieves good entropy, Unified Average Changing Intensity (UACI), and Number of Pixels Change Rate (NPCR) values that reach 7.9960, 33.55%, and 99.65%, respectively.

Purpose: To determine the efficacy of two myopia control contact lenses (CL) compared with a single‐vision (SV) CL. Methods: Ninety‐five Chinese children with myopia, aged 7–13 years in a 1‐year prospective, randomised, contralateral, cross‐over clinical trial with 3 groups; bilateral SVCL (Group I); randomised, contralateral wear of an extended depth of focus (EDOF) CL and SVCL (Group II) and MiSight® CL and SVCL (Group III). In Groups II and III, CL were crossed over at the 6‐month point (Stage 1) and worn for a further 6 months (Stage 2). Group I wore SVCL during both stages. At baseline and the end of each stage, cycloplegic spherical equivalent refractive error (SE) and axial length (AL) were measured. Six‐monthly ΔSE/ΔAL across groups was analysed using a linear mixed model (CL type, stage, eye and eye* stage included as factors). Intra‐group paired differences between eyes were determined. Results: In Group I, mean (SD) ΔSE/ΔAL with SVCL was −0.41 (0.28) D/0.13 (0.09) mm and −0.25 (0.27) D/0.16 (0.09) mm for stages 1 and 2, with a mean paired difference between eyes of 0.01 D/0.01 mm and 0.05 D/−0.01 mm, respectively. ΔSE/ΔAL with SVCL was similar across Groups I to III (Stage 1: p = 0.89/0.44, Stage 2: p = 0.70/ 0.64). In Groups II and III, ΔSE/ΔAL was lower with the EDOF and MiSight® CL than the contralateral SVCL in 68% to 94% of participants, and adjusted 6‐month ΔSE/ΔAL with EDOF was similar to MiSight® (p = 0.49/0.56 for ΔSE/ΔAL, respectively). Discontinuations across the three groups were high, but not different between the groups (33.3%, 48.4% and 50% for Groups I to III, respectively [p = 0.19]) and most discontinuations occurred immediately after baseline. Conclusions: Extended depth of focus and MiSight® CL demonstrated similar efficacy in slowing myopia. When switched from a myopia control CL to SVCL, myopia progression was similar to that observed with age‐matched wearers in SVCL and not suggestive of rebound. [ABSTRACT FROM AUTHOR]

In recent years, Taylor's law describing the power function relationship between the mean and standard deviation of certain phenomena has found an increasing number of applications. We studied the characteristics of Taylor's law for branded product sales using point-of-sale (POS) data for brands sold in 72 grocery stores in the Greater Tokyo area. A previous study found that product sales follow Taylor's law with a scaling exponent of 0.5 for low sales quantities and 1.0 for large sales quantities. In the current study, we observed Taylor's law with cross-over for 54 product brands and estimated the value of the two coefficients in the theoretical curve to characterize the cross-over. The coefficients represent the fluctuations in the number of items purchased per consumer and the number of consumers in one store and in all stores. The estimated coefficients suggested the dependence of the features of Taylor's law on the category to which the brands belong. We found that brands in the same category tend to share similar features under Taylor's law. However, some brands exhibited specific features that differed from others in the same category. For example, for many brands in the Laundry Detergent and Instant Noodles categories, the number of customers purchasing the products in each store fluctuated significantly, whereas the number of purchased items per customer varied widely in the Japanese Tea category. In the coffee category, our results indicated that the degree of fluctuation in the number of purchasing customers largely depends on the brand. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this cross-over investigation was to analyze the effect of virtual teaching using virtual reality (VR) within a dental learning environment by preclinical students with or without dental professional experience on test performance.Methods: Preclinical students (N = 82) were randomly divided into two groups for cross-over testing of tooth morphology knowledge: (a) anterior VR-group (group 1) using the VR-glasses as an additional learning tool for the anterior tooth morphologies and (b) posterior VR-group (group 2) using it for the posterior tooth morphologies also in addition to conventional learning. All students used the VR-glasses for 1 week independent of time and location depending on group. The students had to recognize teeth (anterior or posterior within two separate tests after three [anterior test] and 6 weeks [posterior test] of practical course) and note the tooth number and characteristics in written form. Former dental experience (dental technician/assistance) was noted. Test results were analyzed to quantify the effect of virtual teaching on test scores. Data were analyzed with the Kolmogorov-Smirnov and Mann-Whitney U test (p = 0.05).Results: By differentiating the two student groups (use of VR glasses for anterior/posterior teeth) within the dental experience group, significantly better test results (p = 0.040) were shown for group 1 in the total posterior teeth test score. Furthermore, no other significant differences, but a possible tendency, in the test results and thus no effect of the use of the VR glasses on both VR groups could be analyzed (p ≥ 0.051).Conclusions: Using the VR tooth learning environment predominantly did not lead to a significant improvement of test results. Anterior teeth test scores predominantly showed significantly better results than posterior teeth test scores. [ABSTRACT FROM AUTHOR]

Background: Phelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot study was to further investigate the safety and efficiency of rhGH in patients with PMS. Methods: A total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot study Results: Compared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later. Conclusions: In summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1. [ABSTRACT FROM AUTHOR]

An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing the estimand framework. This new framework aims to align trial objectives and statistical analyses by requiring a precise definition of the inferential quantity of interest, that is, the estimand. This definition explicitly accounts for intercurrent events, such as switching to new anticancer therapies for the analysis of overall survival (OS), the gold standard in oncology. Traditionally, OS in confirmatory studies is analyzed using the intention‐to‐treat (ITT) approach comparing treatment groups as they were initially randomized regardless of whether treatment switching occurred and regardless of any subsequent therapy (treatment‐policy strategy). Regulatory authorities and other stakeholders often consider ITT results as most relevant. However, the respective estimand only yields a clinically meaningful comparison of two treatment arms if subsequent therapies are already approved and reflect clinical practice. We illustrate different scenarios where subsequent therapies are not yet approved drugs and thus do not reflect clinical practice. In such situations the hypothetical strategy could be more meaningful from patient's and prescriber's perspective. The cross‐industry Oncology Estimand Working Group (www.oncoestimand.org) was initiated to foster a common understanding and consistent implementation of the estimand framework in oncology clinical trials. This paper summarizes the group's recommendations for appropriate estimands in the presence of treatment switching, one of the key intercurrent events in oncology clinical trials. We also discuss how different choices of estimands may impact study design, data collection, trial conduct, analysis, and interpretation. [ABSTRACT FROM AUTHOR]

Abstract Skin care against aggravating factors is important to prevent skin lesions from flare‐up in the treatment of atopic dermatitis (AD). Tannic acid (TA), a natural polyphenolic and protein‐denaturing agent, has activity to denature antigens relevant to the AD flare. To assess the efficacy of a bath additive containing TA (TA‐bath additive) on pruritus of AD, we carried out a randomized double‐blind trial, in which 21 patients with AD completed the blinded sequential treatments with the TA‐bath additive and a bath additive without TA (placebo‐bath additive) in a cross‐over manner. A significant improvement of pruritus was observed in the afternoon and night by using the TA‐bath additive and in the afternoon by the placebo‐bath additive in patients with AD. No superiority of the TA‐bath additive to the placebo was revealed in the overall patient cohort. However, the added TA in the bath additive exerted its efficacy especially on itch at night in patients with mild‐to‐moderate disease. Bathing by using the series of the bath additive with TA and that without TA improved AD skin lesions throughout this study. No adverse effects related to the use of the TA‐ and placebo‐bath additives were observed. In conclusion, the bath additive containing TA may help skin care of patients with itch and skin lesions of the mild AD.

BackgroundPhelan-McDermid syndrome (PMS), also known as the 22q13. 3 deletion syndrome, is a rare neurodevelopmental syndrome with approximately 2,800 patients reported worldwide. Previous pilot study demonstrated that IGF-1 could significantly improve in both social impairment and restrictive behaviors of the patients. However, most of the patients in the developing countries like China cannot afford the high cost of using IGF-1. Our research team speculated that rhGH might serve as a low-cost and more accessible treatment for PMS. Therefore, the purpose of this open-label, cross-over, pilot study was to further investigate the safety and efficiency of rhGH in patients with PMS.MethodsA total of six children with PMS were enrolled in in this open-label, cross-over, pilot study. The children were randomly divided into two different groups. Group A received placebo followed by rhGH, while group B was treated with rhGH first. Neuropsychological and behavior assessments of the patients were performed before the stage I of study and 3 months after the intervention of stage I. After a 4-week period of washout, these assessments were conducted again before the stage II of study and 3 months after the intervention of stage II. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding-protein (IGFBP)-3 were also evaluated monthly during the intervention phases of the pilot studyResultsCompared with the placebo, rhGH treatment significantly decreased subscale scores of GDS (P < 0.0085) and trended to improve the total scores of GDS (P < 0.05), while the total scores and subscale scores of SC-ABC significantly decreased (P < 0.0085) following 3-months rhGH treatment. The similar results were also observed in comparison with baseline. Compared with the baseline, the level of serum IGF-1 and IGFBP-3 increased significantly (P < 0.05) following 3-months rhGH treatment, while the placebo group had no significant impact on serum IGF-1 and IGFBP-3 (P > 0.05). One child developed skin allergy the day after the first rhGH treatment, which were resolved later.ConclusionsIn summary, this pilot study involving six PMS children patients reveals that rhGH has a positive treatment effect on PMS. These results encourage the undertaking of a large, randomized placebo-controlled trial to conclusively prove rhGH efficacy and tolerability in PMS, thereby promoting it as a low-cost, more accessible treatment for PMS, as compared to IGF-1.

Fixing the genomic composition and multiplication through true potato seed (TPS) is an important challenge in autotetraploid potato. Disrupted meiotic cDNA (DMC1) is a meiotic gene that plays a central role in DNA recombination through crossing over in meiosis. Using the Arabidopsis DMC1 (AtDMC1) gene sequence, we retrieved Solanum tuberosum DMC1(StDMC1) from the diploid potato genome, and subsequently, sense and antisense regions of the StDMC1 gene were amplified in potato cv. Kufri Jyoti. The sense and antisense fragments were confirmed by Sanger-sequencing and cloned in the pRI101 vector. Agrobacterium-mediated transformation of the RNAi construct resulted in 44% transformation efficiency, and a total of 137 mutant lines were obtained. These mutant lines were further validated through pollen viability testing, and selected lines were used for gene expression analysis. The acetocarmine-based pollen staining showed reduced pollen viability ranging from 14 to 21% in four DMC1 mutant lines (DMC4-37, DMC4-41, DMC6-20, and DMC6-21), as compared to the Kufri Jyoti control plants, which on average exhibited 78% pollen viability. The phenotypic data was supported by the reduced expression of the StDMC1 gene in these four mutant lines compared to the control Kufri Jyoti. The results confirmed the generation of StDMC1 knockdown lines. This is the first report of StDMC1 mutant line generation in tetraploid potatoes and will be a step forward in generating non-recombinant mutants through sexual reproduction in potatoes.

Background: The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) recommend the consumption of less than 2,000 mg of sodium/day to reduce blood pressure and the risk of conditions such as cardiovascular disease and coronary heart disease. The sodium intake among Vietnamese was reported to be 7,200 mg/d or more. Free L-glutamate enhances flavor when it is added to food and improves the taste of sodium-reduced foods., Objective: This study aims to investigate whether the intake of free L-glutamate-rich seasonings contributes to maintaining a low sodium intake in a cross-over study., Methods: From a total of 145 subjects, 42 participants were screened for participation in the cross-over design study. Subjects were randomly allocated to the Low free L-glutamate group (Low free L-Gl) and the Normal free L-glutamate group (Normal free L-Gl). Both received a direct educational guideline to reduce sodium intake. The Low free L-Gl group started with a restriction in the variety of free L-glutamate-rich seasonings, and the Normal free L-Gl group had no restriction in the variety of seasonings. Blood pressure was measured at week 0 (baseline), week 2, week 4, and week 6, while body weight, height, urine sodium and potassium excretion, chromogranin-A (CgA pmol/mg protein) from saliva, and free L-glutamate from food were measured at week 0, week 3, and week 6., Results: In Low free L-Gl, the amount of free L-glutamate in food decreased significantly from baseline to week 6 ( p  < 0.00), while it did not change in the Normal free L-Gl ( p  > 0.05). However, the reduction of sodium excretion at week 6 was 22% in Low free L-Gl (5,875 mg/d vs. 4,603 mg/d, p  < 0.01) and 46% in Normal free L-Gl (6,107 mg/d vs. 3,277 mg/d, p  < 0.00), both lower than the baseline. CgA (pmol/mg protein) did not show any difference between the two groups., Conclusion: The group with Normal free L-Gl intake showed a 46% reduction in sodium excretion by week 6 compared to the baseline. This suggests that the consumption of L-glutamate-rich seasonings when complemented with direct educational guidelines, can contribute to maintaining a low sodium intake., Competing Interests: AW, HM, and HU were employed by Ajinomoto Co., Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hien, Tuyen, Wakita, Shikanai, Hang, Anh, Nguyet, Iwamoto, Matsumoto, Uneyama, Son, Linh and Yamamoto.)

Individuals with a recent anterior cruciate ligament reconstruction may demonstrate an altered movement strategy for protecting the knee and maintaining stability. Altered knee movement might lead to abnormal intra-articular load, potentially contributing to early knee osteoarthritis onset. A protective strategy may be particularly evident during active tasks that induce a pivot-shift manoeuvre, such as a step-down and cross-over task. In this study, we investigated whether knee joint mechanics and muscle activity differed between participants early (∼3 months) following reconstruction (n = 35) to uninjured controls (n = 35) during a step-down and cross-over task with a 45° change-of-direction. We used motion capture, force plates and surface electromyography to compare time-normalised curves of sagittal and transverse-plane knee mechanics and muscle activity during the cross-over phase between groups using functional t -tests. We also compared knee mechanics between sides within the injured group and compared discrete outcomes describing the cross-over phase between groups. Compared to controls, the injured participants had greater knee flexion angle and moment, lower internal rotation moment, more preparatory foot rotation of the pivoting leg, a smaller cross-over angle, and a longer cross-over phase for both the injured and uninjured sides. The injured leg also had greater biceps femoris and vastus medialis muscle activity compared to controls and different knee mechanics than the uninjured leg. Individuals with anterior cruciate ligament reconstruction showed a knee-stabilising and pivot-shift avoidance strategy for both legs early in rehabilitation. These results may reflect an altered motor representation and motivate considerations early in rehabilitation. • A unilateral anterior cruciate ligament injury is a double-leg problem. • Injured persons revealed a knee-protective strategy ∼3 months after reconstruction. • They demonstrated atypical knee mechanics for both legs compared to controls. • They also revealed asymmetric knee mechanics, but less clear than to controls. [ABSTRACT FROM AUTHOR]

Abstract Background Osteoarthritis (OA) affects nearly 20% of all dogs greater than one year of age. Clinical signs include pain, discomfort, lameness, and ultimately lead to disability. Although there is currently no known cure, there are many therapeutic options that can slow the progression and alleviate the associated signs. There is ample supportive evidence demonstrating the efficaciousness of carprofen, a non-steroidal anti-inflammatory drug, in managing signs of OA. Since the approval of the pioneer product (Rimadyl®, Zoetis; Kalamazoo, Michigan), the United States Food and Drug Administration (FDA) has assented to several other generic, bioequivalent products. The objective of this 2 × 2 complete cross-over design was to assess the acceptance of two bioequivalent carprofen liver-flavored chewable tablets (containing 25 mg carprofen), Rimadyl® and Carprieve® (Norbrook Laboratories Limited; Newry, Northern Ireland) in 37 healthy purpose-bred dogs. Results Overall, 73.0% (27/37) and 70.3% (26/37) of dogs voluntarily accepted Rimadyl® and Carprieve®, respectively. Considering acceptability tests paired by individual dog, 64.9% of dogs (n = 24) voluntarily accepted both Rimadyl® and Carprieve® chewable tablets whereas 21.6% (8) of dogs denied or partially accepted both products offered. Three dogs (8.1%) fully accepted Rimadyl® but did not accept Carprieve®. Conversely, two dogs (5.4%) fully accepted Carprieve® but did not accept Rimadyl®. Canine acceptability did not significantly differ between Carprieve® and Rimadyl® carprofen chewable tablets (P = 0.65). Conclusions Utilizing a 2 × 2 complete cross-over design, this study provides evidence that canine acceptability of a single-dose did not differ between Carprieve® and Rimadyl® chewable tablets.

Background: Accurately assessing an individual's diet is vital in the management of personal nutrition and in the study of the effect of diet on health. Despite its importance, the tools available for dietary assessment remain either too imprecise, expensive, or burdensome for clinical or research use. Image-based methods offer a potential new tool to improve the reliability and accessibility of dietary assessment. Though promising, image-based methods are sensitive to adherence, as images cannot be captured from meals that have already been consumed. Adherence to image-based methods may be improved with appropriately timed prompting via text message., Objective: This study aimed to quantitatively examine the effect of prompt timing on adherence to an image-based dietary record and qualitatively explore the participant experience of dietary assessment in order to inform the design of a novel image-based dietary assessment tool., Methods: This study used a randomized crossover design to examine the intraindividual effect of 3 prompt settings on the number of images captured in an image-based dietary record. The prompt settings were control, where no prompts were sent; standard, where prompts were sent at 7:15 AM, 11:15 AM, and 5:15 PM for every participant; and tailored, where prompt timing was tailored to habitual meal times for each participant. Participants completed a text-based dietary record at baseline to determine the timing of tailored prompts. Participants were randomized to 1 of 6 study sequences, each with a unique order of the 3 prompt settings, with each 3-day image-based dietary record separated by a washout period of at least 7 days. The qualitative component comprised semistructured interviews and questionnaires exploring the experience of dietary assessment., Results: A total of 37 people were recruited, and 30 participants (11 male, 19 female; mean age 30, SD 10.8 years), completed all image-based dietary records. The image rate increased by 0.83 images per day in the standard setting compared to control (P=.23) and increased by 1.78 images per day in the tailored setting compared to control (P≤.001). We found that 13/21 (62%) of participants preferred to use the image-based dietary record versus the text-based dietary record but reported method-specific challenges with each method, particularly the inability to record via an image after a meal had been consumed., Conclusions: Tailored prompting improves adherence to image-based dietary assessment. Future image-based dietary assessment tools should use tailored prompting and offer both image-based and written input options to improve record completeness., (© Lachlan Lee, Rosemary Hall, James Stanley, Jeremy Krebs. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Aim: To assess the impact of purchasing wine in 50 cl bottles compared with 75 cl bottles on the amount of wine consumed at home. Design Cross‐over randomized controlled trial with a 'usual behaviour' period of a maximum of 3 weeks between conditions. Setting: Households in the United Kingdom. Participants: One hundred and eighty‐six households that consumed between two and eight 75 cl bottles of wine each week. Intervention: Households were randomized to the order in which they purchased wine in two bottle sizes. During two 14‐day intervention periods, households purchased a pre‐set volume of wine—based on their baseline self‐reported weekly consumption—in either 75 cl bottles or 50 cl bottles. On days 7 and 14 of each study period, participating households sent photographs of each purchased wine bottle. Measurements The primary outcome was the volume of study wine in millilitres (ml) consumed during each study period estimated through returned photographs. The secondary outcome was the rate of consumption measured by the mean number of days taken to drink 1.5 litres from each bottle size. Findings One hundred and sixty‐six of 186 enrolled households satisfactorily completed the study. After accounting for pre‐specified covariates, 191.1 ml [95% confidence interval (CI) = 42.03–339.2] or 4.5% (95% CI = 1.0–7.9%) more wine was consumed per 14‐day period from 75‐cl bottles than from 50‐cl bottles. Consumption was 5.8% faster (95% CI = –10.9 to –0.4%) from 75 cl bottles than from 50 cl bottles. Conclusions: Consuming wine at home from 50 cl bottles, compared with 75 cl bottles, may reduce both amount consumed and rate of consumption. [ABSTRACT FROM AUTHOR]

Skin care against aggravating factors is important to prevent skin lesions from flare‐up in the treatment of atopic dermatitis (AD). Tannic acid (TA), a natural polyphenolic and protein‐denaturing agent, has activity to denature antigens relevant to the AD flare. To assess the efficacy of a bath additive containing TA (TA‐bath additive) on pruritus of AD, we carried out a randomized double‐blind trial, in which 21 patients with AD completed the blinded sequential treatments with the TA‐bath additive and a bath additive without TA (placebo‐bath additive) in a cross‐over manner. A significant improvement of pruritus was observed in the afternoon and night by using the TA‐bath additive and in the afternoon by the placebo‐bath additive in patients with AD. No superiority of the TA‐bath additive to the placebo was revealed in the overall patient cohort. However, the added TA in the bath additive exerted its efficacy especially on itch at night in patients with mild‐to‐moderate disease. Bathing by using the series of the bath additive with TA and that without TA improved AD skin lesions throughout this study. No adverse effects related to the use of the TA‐ and placebo‐bath additives were observed. In conclusion, the bath additive containing TA may help skin care of patients with itch and skin lesions of the mild AD. [ABSTRACT FROM AUTHOR]

Little is known regarding the variables or mechanisms mediating cross-education as a result of resistance training. Therefore, the purpose of the present study was to examine the effects of low-load eccentric-only blood flow restriction (Ecc-BFR) and low-load concentric-only BFR (Con-BFR) on indices of cross-education. Thirty-six women were randomly assigned to 4-wks of unilateral resistance training with Ecc-BFR (n = 12), Con-BFR (n = 12) or control (no intervention, n = 12) group. Eccentric peak torque, concentric peak torque, maximal voluntary isometric contraction torque, muscle thickness, and muscle activation were assessed from the contralateral, untrained arm. Muscle strength (collapsed across mode) increased from 0-wk to 2-wks (4.9%) and 4-wks (13.0%) for Ecc-BFR only. There were increases in muscle activation (collapsed across mode and group) regardless of training modality, but there were no changes in muscle size for any of the conditions. The findings of the present study indicated that low-load Ecc-BFR increased muscle strength. The increases in muscle strength as a result of Ecc-BFR were not mode-specific. Thus, low-load Ecc-BFR provides a unique alternative to maintain muscle function in an untrained limb that may have application during limb immobilization and rehabilitation practices. • Eccentric-only BFR increases muscle strength in an untrained arm. • Increased muscle activation in untrained, contralateral limb. • Eccentric-only BFR increased muscle strength for all modes. • Mode of training, not BFR, affects cross-education. [ABSTRACT FROM AUTHOR]

Background: Due to phenolic and fructose content, honey may be a suitable sweetener for patients with type 2 diabetes. However, its effect on oxidative and inflammatory status of diabetes patients is not clear. We aimed to investigate the effect of natural honey on some of oxidative, inflammatory, and anti-inflammatory markers of patients with type 2 diabetes. Methods: In a randomized controlled cross-over trial, 43 patients with type 2 diabetes were allocated to isocaloric conditions with either dietary recommendations (control) or natural honey (50 g/day) plus dietary recommendations (honey) for 8 weeks with one month washout period in between. Serum lipids, malondialdehyde (MDA), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP), and adiponectin levels were measured at baseline and the end of each sequence. Results: Malondialdehyde (10.9%, P = 0.01), hs-C reactive protein (10.6%, P = 0.003), and adiponectin (7.1%, P < 0.001) concentrations significantly decreased in honey condition. Low-density lipoprotein cholesterol (LDL-C) (16.8%, P < 0.001) significantly decreased in control and high-density lipoprotein cholesterol (HDL-C) significantly increased in both conditions. Between-group differences were only statistically significant for adiponectin (P = 0.005) and LDL-C (P = 0.005). Conclusions: Consumption of 50 g/day honey had adverse effects on LDL-C and adiponectin levels in patients with type 2 diabetes. Honey may need to be consumed with caution in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Several field/area demands various minimal balance cross-over designs based on relation between treatment, period and subject. However, its construction is sometimes difficult, particularly for the non-mathematician experimenter. The present paper provides a MATLAB program for construction of the minimal balanced cross-over design. This program meets the practical needs of experimenters/users in the application of cross-over design because it provides a variety of cross-over designs for the same class by inputting only two user specified parameters, number of treatments, and number of periods. The MATLAB program constructs cross-over designs for any combination of treatments and periods with its efficiency of separability. Theoretical construction is difficult when number of treatments or periods is large, but through this program experimenter/user easily constructs number of cross-over designs. This program also constructs recently investigated crossover designs. [ABSTRACT FROM AUTHOR]

In the phase 3 ARAMIS study (NCT02200614), darolutamide significantly improved metastasis-free survival in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Following the primary analysis, the study was unblinded, and placebo recipients were permitted to cross over to open-label darolutamide. Despite crossover, darolutamide significantly improved overall survival (OS). We conducted sensitivity analyses to estimate the effect of placebo–darolutamide crossover on OS. Patients with nmCRPC were randomised to oral darolutamide 600 mg twice daily (n = 955) or placebo (n = 554). Prespecified (rank-preserving structural failure time [RPSFT] and iterative parameter estimation [IPE]) and post hoc (OS-adjusted censoring and inverse probability of censoring weighting [IPCW], with weightings for baseline testosterone and prostate-specific antigen) sensitivity analyses were conducted. After unblinding, 170 of 554 placebo recipients (30.7%) crossed over to darolutamide. At the final OS intention-to-treat analysis (median 11.2 months after unblinding), darolutamide significantly improved OS by 31% versus placebo (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.53–0.88; P = 0.003). The benefit increased in the analyses adjusting for crossover is as follows: RPSFT HR 0.68, 95% CI 0.51–0.90; P = 0.007; IPE HR 0.66, 95% CI 0.51–0.84; P < 0.001; OS-adjusted censoring HR 0.59, 95% CI 0.45–0.76; IPCW HR 0.63, 95% CI 0.48–0.81. The favourable safety profile of darolutamide was maintained, including in crossover patients. After adjusting for crossover, darolutamide reduced the risk of death by up to 41% in patients with nmCRPC. The effect of darolutamide on OS may have been underestimated in the original intention-to-treat analysis. • Darolutamide significantly improved metastasis-free survival (MFS) versus placebo in men with nmCRPC. • After the MFS analysis, 170 placebo recipients (31%) crossed over to open-label darolutamide. • In the final analysis, darolutamide reduced the risk of death by 31% (HR 0.69) versus placebo. • Sensitivity analyses indicate a risk reduction for death of up to 41% if crossover had not occurred. • These analyses confirm darolutamide as an effective early treatment option in nmCRPC. [ABSTRACT FROM AUTHOR]

Hypertensive patients who adopt a sodium-restricted diet have difficulty maintaining this change, and this could increase stress. On the other hand, soup rich in umami substances (dashi) was reported to reduce indexes of anxiety and stress. The objective of this study was to measure mood and physiological stress indexes during administration of a sodium-restricted diet with and without an umami substance (free L-glutamate) by a cross-over randomized, single-blind, placebo-controlled trial in Japanese female university students. The baseline was measured for 5 days followed by a sodium-restricted diet intervention phase that lasted for 10 days. The Profile of Mood States questionnaire was administered, a stress marker in saliva (chromogranin-A) was measured, and the amount of sodium intake was confirmed from 24 h urine collection samples. Results showed that the sodium reduction was verified by 24 h urine excretion. The percentage of change in the stress marker from the baseline showed that the stress level in group without the umami substance was significantly higher than that in the group with the umami substance (p = 0.013) after receiving a sodium-reduced diet for 6 or more days, indicating that stress was alleviated. This study suggested that umami substances might help to ameliorate stress during a sodium-reduced diet, especially in the initial phase.

The use of cluster randomized trial design to answer research questions is increasing. This design and associated variants such as the cluster randomized crossover and stepped wedge are useful to assess complex interventions in a pragmatic way but when adopting such designs, one may face specific implementation challenges. This article summarizes common challenges faced when conducting cluster randomized trials, cluster randomized crossover trials, and stepped wedge trials, and provides recommendations., Competing Interests: Declaration of competing interest The authors declare they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)