Restricted Procedure Research Articles

Evaluating animal models comprising additive genetic and maternal effects on growth traits in German Angora rabbit

This investigation was carried out to estimate the genetic parameters for German Angora rabbits using most appropriate animal model comprising additive and maternal effects. The pedigree information and data on growth traits were collected from 5221 rabbits, which descended from 699 does and 294 bucks over a period of 21 yr (2001–2021) kept at Northern Temperate Regional Station, Garsa, Kullu (Himachal Pradesh), India. The average daily gain (ADG) and Kleiber ratio (KR) were calculated at different age intervals. Analyses were carried out by restricted maximum likelihood procedure fitting six animal models with various combinations of direct and maternal effects. The best model was evaluated on the basis of a likelihood ratio test. Analysis revealed that the model including both direct and maternal genetic effects along with permanent effect of the dam was most suitable for all traits except for body weight (BW) at 6th wk of age, ADG from 6th to 12th wk of age and KR associated to ADG from 12th to 18th wk of age. The direct heritability estimates from the best model were ranged from, 0.34±0.05 to 0.49±0.05 for BW; 0.19±0.04, to 0.46±0.06 for ADG and 0.21±0.04 to 0.41±0.05 for KR, respectively. Direct heritability estimates were overestimated when maternal effects were ignored. Maternal effects on BW declined from 0.49±0.04 at weaning to 0.06±0.03 at 12th wk of age and 0.09±0.04 at 18th wk of age. Correlations between direct and maternal effects ranged from −0.44±0.15 to−0.52±0.14 for body weights, indicating biological antagonism between these effects. Genetic correlations among various growth traits were positive and high, indicating scope for correlated response in later expressed traits. Analysis revealed that maternal additive influences were only important until weaning, whereas permanent environmental maternal influences were present in all growth traits considered in this study. The moderate estimates of heritability for growth traits and Kleiber ratio of rabbit in this study indicate that rates of genetic progress may be possible for these traits by selection under the standard management system.

Study of body measurements and components of variance for various body measurements of goats found in Southern Punjab

Variance components are estimated to further compute genetic parameters, and these components reflect variation of traits as well as their transferability to the next generation. This study was conducted to estimate variance components for different body measurements in Teddy goats in the southern Punjab. Data were subjected to mixed model analysis using ASReml software where restricted maximum likely hood procedure was adopted. These body measurements included diagonal body length, withers height, head length, neck length, ear length, ear width, tail length, distance between ears, and canon circumference. Body measurements were recorded using tailor tape and live weight will be measured by spring balance. The following form of animal model was applied; Yijklm= YOBi+ SOBj + Sexk + TOBl + A +Ԑijklm.. The estimates for variance components were used to compute genetic parameters.

Estimation of (co)variance components for body weight traits in intercross synthetic sheep

This study was carried out on the recently developed intercross sheep developed from Bharat merino and Gaddi sSynthetic in the temperate region in the state of Himachal Pradesh of India. Study aimed to estimate the genetic parameters and (co)variance components for body weights at birth (BW) and 3-month (3BW), 6-month (6BW), 9-month (9BW) and 12-month (12BW) month age in a closed flock of intercross sheep maintained at North Temperate Regional Station of ICAR-CSWRI, Garsa, India. Data records on 1505 sheep descended from 565 dams and 154 sires over the period of 10 years were utilized. Data were corrected for possible fixed environmental effects such as lambing year, parity, sex of lamb, ewe weight at lambing for further genetic analysis. The restricted maximum likelihood procedure fitting animal models with different combinations of direct and maternal effects were used for genetic analysis. Analysis revealed significant influences of lambing year, parity, sex of lamb and ewe weight at lambing on studied traits. Direct heritability estimates for BW, 3BW, 6BW, 9BW and 12BW were 0.14±0.04, 0.18±0.05, 0.00±0.04, 0.05±0.05 and 0.05±0.05, respectively. Maternal effects significantly influenced the BW and estimated maternal heritability for the trait was 0.17±0.03. The correlation among body weights were medium to high except between BW and 12BW and it ranged from 0.16±0.51 to 0.99±0.19. Results suggest that maternal effects were important for initial growth performance. The heritability estimates for weaning weight was moderate and its positive association with other growth traits indicated that the present selection practice at six months may be shifted to early selection at weaning weight for further genetic improvement.

Population diversity control based differential evolution algorithm using fuzzy system for noisy multi-objective optimization problems

The objective measurements of the real-world optimization problems are mostly subject to noise which occurs due to several reasons like human measurement or environmental factors. The performance of the optimization algorithm gets affected if the effect of noise is higher than the negligible limit. The previous noise handling optimization algorithms use a large population size or multiple sampling at same region which increases the total count of function evaluations, and few methods work for a particular problem type. To address the above challenges, a Differential Evolution based Noise handling Optimization algorithm (NDE) to solve and optimize noisy bi-objective optimization problems is proposed. NDE is a Differential Evolution (DE) based optimization algorithm where the strategies for trial vector generation and the control parameters of DE algorithm are self-adapted using fuzzy inference system to improve the population diversity along the evolution process. In NDE, explicit averaging based method for denoising is used when the noise level is higher than negligible limit. Extending noise handling method enhances the performance of the optimization algorithm in solving real world optimization problems. To improve the convergence characteristics of the proposed algorithm, a restricted local search procedure is proposed. The performance of NDE algorithm is experimented using DTLZ and WFG problems, which are benchmark bi-objective optimization problems. The obtained results are compared with other SOTA algorithm using modified Inverted Generational Distance and Hypervolume performance metrics, from which it is confirmed that the proposed NDE algorithm is better in solving noisy bi-objective problems when compared to the other methods. To further strengthen the claim, statistical tests are conducted using the Wilcoxon and Friedman rank tests, and the proposed NDE algorithm shows significance over the other algorithms rejecting the null hypothesis.

Understanding an impact of patient enrollment pattern on predictability of central (unstratified) randomization in a multi-center clinical trial.

In a multi-center randomized controlled trial (RCT) with competitive recruitment, eligible patients are enrolled sequentially by different study centers and are randomized to treatment groups using the chosen randomization method. Given the stochastic nature of the recruitment process, some centers may enroll more patients than others, and in some instances, a center may enroll multiple patients in a row, for example, on a given day. If the study is open-label, the investigators might be able to make intelligent guesses on upcoming treatment assignments in the randomization sequence, even if the trial is centrally randomized and not stratified by center. In this paper, we use enrollment data inspired by a real multi-center RCT to quantify the susceptibility of two restricted randomization procedures, the permuted block design and the big stick design, to selection bias under the convergence strategy of Blackwell and Hodges (1957) applied at the center level. We provide simulation evidence that the expected proportion of correct guesses may be greater than 50% (i.e., an increased risk of selection bias) and depends on the chosen randomization method and the number of study patients recruited by a given center that takes consecutive positions on the central allocation schedule. We propose some strategies for ensuring stronger encryption of the randomization sequence to mitigate the risk of selection bias.

A New Approach to Public Contracting of Sustainable Construction Using Innovation Partnership

Sustainable public procurement of construction projects is a key objective to fulfill the targets of the EU Green Deal, the new Regulation approved by the European Parliament, and the conditions required by the Facility of Recovery and Resilience approved by EU. However, most of the adopted procedures are based on traditional procedures, open competition, or restricted procedures, which are not appropriate for developing an innovative approach aiming for more ambitious sustainable objectives. Innovation partnership is a new procedure introduced by the EU Directives of Public Procurement of 2014 ( Article 31º of 2014/24/UE), and it has been discussed and applied to the development of new products but, unfortunately, its potential has not been studied as a tool to prepare and to award more innovative and sustainable contracts of public works. This is the objective of the research presented in this paper, and a set of guidelines is deduced and discussed to support public contracting authorities to make better use of innovation partnerships.

Evaluation of models for estimation of genetic parameters for post-weaning body measurements and their association with yearling weight in Nellore sheep.

The objective of this study was to obtain (co) variance components and genetic parameter estimates for post-weaning body measurements such as body length (BL), height at withers (HW), and chest girth (HG) recorded at six (SBL, SHW, and SHG), nine (NBL, NHW, and NHG) and twelve (YBL, YHW, and YHG) months of age along with yearling weight (YW) in Nellore sheep maintained at livestock research station, Palamaner, Andhra Pradesh, India and also the association among body measurements with YW was studied. Data on 2,076 Nellore sheep (descended from 75 sires and 522 dams) recorded between 2007 and 2016 (10 years) were utilized in the study. Lambing year, sex of lamb, season of lambing and parity of dam were included in the model as fixed effects and ewe weight was kept as a covariate. Analyses were conducted with six animal models with different combinations of direct and maternal genetic effects using restricted maximum likelihood procedure. Best model for each trait was determined based on Akaike's information criterion. Moderate estimates of direct heritability were obtained for the studied traits viz., BL (0.02 to 0.24), HW (0.31 to 0.49), and CG (0.08 to 0.35) and their corresponding maternal heritability estimates were in the range of 0.00 to 0.07 (BL), 0.13 to 0.17 (HW), and 0.07 to 0.13 (CG), respectively. Positive direct genetic and phenotypic correlations among the traits and they ranged from 0.07 (YBL-YW) to 0.99 (SBL-SHG, SHG-YW, and NBL-YBL) and 0.01 (SBL-YBL) to 0.99 (NBL-NHG), respectively. Further, the genetic correlations among all the body measurements and YW were positive and ranged from 0.07 (YW and YBL) to 0.99 (YW and SHG). There was a strong association of chest girth at six months with YW. Further, it is indicated that moderate improvement of post-weaning body measurements in Nellore sheep would be possible through selection.

The Identification of a Quantative Trait Loci-Allele System of Antixenosis against the Common Cutworm (Spodoptera litura Fabricius) at the Seedling Stage in the Chinese Soybean Landrace Population.

Common cutworm (CCW) is an omnivorous insect causing severe yield losses in soybean crops. The seedling-stage mini-tray identification system with the damaged leaf percentage (DLP) as an indicator was used to evaluate antixenosis against CCW in the Chinese soybean landrace population (CSLRP) under three environments. Using the innovative restricted two-stage multi-locus genome-wide association study procedure (RTM-GWAS), 86 DLP QTLs with 243 alleles (2-11/QTL) were identified, including 66 main-effect loci with 203 alleles and 57 QTL-environment interaction loci with 172 alleles. Among the main-effect loci, 12 large-contribution loci (R2 ≥ 1%) explained 25.45% of the phenotypic variation (PV), and 54 small-contribution loci (R2 < 1%) explained 16.55% of the PV. This indicates that the CSLRP can be characterized with a DLP QTL-allele system complex that has not been found before, except for a few individual QTLs without alleles involved. From the DLP QTL-allele matrix, the recombination potentials expressed in the 25th percentile of the DLP of all possible crosses were predicted to be reduced by 41.5% as the maximum improvement and 14.2% as the maximum transgression, indicating great breeding potential in the antixenosis of the CSLRP. From the QTLs, 62 candidate genes were annotated, which were involved in eight biological function categories as a gene network of the DLP. Changing from susceptible to moderate plus resistant varieties in the CSLRP, 26 QTLs had 32 alleles involved, in which 19 genes were annotated from 25 QTL-alleles, including eight increased negative alleles on seven loci and 11 decreased positive alleles on 11 loci, showing the major genetic constitution changes for the antixenosis enhancement at the seedling stage in the CSLRP.

Balancing the Objectives of Statistical Efficiency and Allocation Randomness in Randomized Controlled Trials

Various restricted randomization procedures are available to achieve equal (1:1) allocation in a randomized clinical trial. However, for some procedures, there is a nonnegligible probability of imbalance in the final numbers which may result in an underpowered study. It is important to assess such probability at the study planning stage and make adjustments in the design if needed. In this article, we perform a quantitative assessment of the tradeoff between randomness, balance, and power of restricted randomization designs targeting equal allocation. First, we study the small-sample performance of biased coin designs with known asymptotic properties and identify a design with an excellent balance–randomness tradeoff. Second, we investigate the issue of randomization-induced treatment imbalance and the corresponding risk of an underpowered study. We propose two risk mitigation strategies: increasing the total sample size or fine-tuning the biased coin parameter to obtain the least restrictive randomization procedure that attains the target power with a high, user-defined probability for the given sample size. Additionally, we investigate an approach for finding the most balanced design that satisfies a constraint on the chosen measure of randomness. Our proposed methodology is simple and yet generalizable to more complex settings, such as trials with stratified randomization and multi-arm trials with possibly unequal randomization ratios.

Genetic parameters for lifetime productivity in Holstein and Brown Swiss dairy cows in Honduras

Objective. To estimate the heritability (h2) of age at first parturition (AFP), longevity (L), useful life (UL), and productivity (P), as well as the genetic (rg) and phenotypic correlations between those traits in Brown Swiss and Holstein cows in Northwestern Honduras. Materials and methods. Cattle were raised under tropical conditions and intensive management. The model for AFP assessed the effect of contemporary group (herd, year and birth season combination) as fixed. The model used for L, UL and P included the contemporary group, age group at first calving and their interaction. Data were analyzed using restricted maximum likelihood procedure, adjusted to a univariate and to a bivariate animal model. Results. The h2 estimated for AFP, L, UL and P were 0.16, 0.18, 0.25 and 0.09, respectively, in Brown Swiss cows, and 0.53, 0.49, 0.7 and 0.22, respectively in Holstein. Negative but favorable rg among Brown Swiss cow traits ranged from 0.31 to 0.46 between AFP and the other traits. However, for Holsteins cows, positive rg among AFP and the other traits here studied varied from 0.49 to 0.96. In both cattle breeds, rg among L, UL and P, traits were positive. Conclusions. For all traits evaluated low to medium heritability’s for BS suggest that a slow genetic improvement could be achieved if independent selection of traits is applied, and better response could be expected for H breed. For both breeds the positive rg among L, UL and P suggest thar similar selection criteria could be used.

Effect of ewe birth litter size and estimation of genetic parameters on ewe reproductive life traits.

Ewe lifetime productivity has economic implications for producers because shorter lifetime productivity results in less profit. Productive years of ewes from extensive, range-based systems of the United States West are generally less than ewes from more temperate regions of the United States. Accordingly, ewes from range-based systems, especially those employing shed-lambing strategies, have been selected for increased litter size to offset decreased lifetime productivity. However, the relationship of the ewe's birth litter size (ELSB) has not been considered a potential contributor to lifetime productivity. Longevity (number of productive years, n=1 per population) and stayability (probability to survive to the next age; ages 2-7years, n=6 per population) were investigated to understand ELSB effects on productive life. Columbia, Polypay, Rambouillet, and Targhee breeds were used in this study. Across-breed (n=11550) and within-breed (Columbia, n=4398; Polypay, n=4534; Rambouillet, n=5922; Targhee, n=6482) analyses were used. Depending on the population, records spanned from 1950 to 2008, where ewe's birth year was included as a fixed effect in the animal model using restricted maximum likelihood estimation procedures. Fixed effects investigated included ELSB (single-, twin-, or triplet-born) and ewe breed (across-breed analyses only). Regardless of trait or population used, heritability ranged from 0.06±0.02 to 0.34±0.03, where stayability at younger ages had the highest estimates. The breed effect was significant in all across-breed analyses (0.0001≤P≤0.038; n=7), where Polypay, a breed selected for accelerated lambing and increased fertility, averaged shorter productive life or had a lower probability of survival to the next age compared with other breeds (longevity: 0.009≤P≤0.223; stayability: 0.000≤P≤0.842). The ELSB was significant in 60% (n=5) and 37% (n=30) of longevity and stayability analyses, respectively. Except for Targhee, all analyses showed ewes born in smaller litter sizes were associated with longer productive lives or higher probability of surviving to the next age, particularly in across-breed analyses (e.g., longevity: single- vs twin-born ewes, P=0.004; vs triplet-born ewes, P=0.003). This study provides evidence that increasing prolificacy in ewes from extensive, range-based production systems may impact productive life. Due to the low heritability of these traits, additional investigation into modeling these traits with dominance effects and litter size needs to be conducted.

Assessment of efficacy of drug evaluation and classification program in Florida

Objective The present study aims to assess the effectiveness of the Drug Evaluation and Classification (DEC) program in Florida. Methods Data from 236 completed DEC evaluations of central nervous system (CNS) depressants, CNS stimulants, narcotic analgesics, and cannabis were analyzed using a classification process comprising toxicology findings and corresponding Drug Recognition Expert (DRE) opinions. A series of standard measures (sensitivity, specificity, false-alarm rate, miss rate, corroboration, and accuracy) were calculated to assess the effectiveness of the DEC program. Results DREs provided 172 correct opinions and 23 missed opinions, resulting in an accuracy rate of 88%, sensitivity rate of 97%, specificity rate of 23%, false alarm rate of 77%, miss rate of 3%, and corroboration rate of 91%. The 12-step DRE protocol of the DEC program therefore has the desired effect of DREs formulating correct opinions. The specificity and false alarm rate were influenced by the restricted testing procedures in the state of Florida. In general, law enforcement officers certified in the DEC program with specialized training can identify drugged drivers and the correct drug category of the drug causing impairment at the time of operating a vehicle. The DEC program goals are met through rigorous training and a curriculum establishing the 12-step DRE protocol. Conclusions DRE drug classification opinions identify drugged drivers. The limitations of Florida’s biological sample testing procedures have an impact on the specificity of DRE opinions. Addressing these limitations could increase the confirmation rates of the presence of drugs in the individual’s biological samples, which would directly impact the conviction rates in DUI-related criminal cases. Further Florida’s testing procedures need to be further studied and updated to improve the DEC program in Florida.

Genetic and phenotypic parameter estimates for selection within Ugandan indigenous chickens

The high genetic variation within indigenous chickens (IC) which provides an opportunity to select superior stock for sustainable production and conservation is under-exploited. This study is aimed at estimating heritability and genetic and phenotypic correlation coefficients of productive and reproductive traits of Ugandan IC as a basis for selection. Data on traits were collected across two consecutive generations, weight (W) and shank length (SL) of chicks at hatching (HW) as well as at 2 (W2; SL2), 4 (W4; SL4), 6 (W6; SL6), 8 (W8; SL8), and 12 (W12; SL12) weeks of growth. Body weights at onset of lay (WFE) were also measured. In addition, egg number (EN-60), egg weight (EW), clutch number (CLN-60), and clutch size (CLS-60) over a period of 60 days were recorded. Genetic parameters were estimated using the univariate animal model analysis with restricted maximum likelihood procedure using the variability package of R, version 4.1.1. Heritability of traits ranged from 0.30 and 0.72 except SL4 (0.02), SL12 (0.14), and EN-60 (0.17). The traits EN-60 and W4 were negatively phenotypically correlated (- 0.49). Body weight at first egg was highly genetically correlated (0.99) with SL8. Egg number was significantly, negatively, and genetically correlated (- 0.96) with SL12. In conclusion, shank length is a potential phenotypic marker when selecting for live weight at onset of lay and egg yield. The shank length could, therefore, permit selection of superior chickens at an early age.

On competition and transparency in public procurement during the COVID-19 pandemic in the European Union

Government expenditures on acquiring services, goods, and work through public procurement represent a substantial proportion of the EU’s GDP. Competitive and transparent tendering procedures are generally believed to promote achieving the primary goals of public procurement: maximising value for money and reducing corruption. However, during the crisis, procurement rules allow a temporary departure from transparency standards toward fast and more discretionary procurement procedures justified by force majeure, possibly restricting competitiveness and information availability in the whole procurement process. The presented paper examines emergency response procurement measures by EU countries in the aftermath of the COVID-19 outbreak in the spring of 2020 and their impact on competition. Using an extensive dataset of contracts for medical supplies and PPE obtained from Tenders Electronic Daily, we document the rapid increase of direct and negotiated contracts in the first two months of the pandemic outbreak. We found that firms, in general, were more likely to participate in procurement procedures with a prior call for tenders, such as open procedure and restricted procedure. On the other hand, the significant share of contracts obtained by small and medium enterprises without competition, hence by single bid procurement, suggests that public authorities tend to use their discretion in favour of SMEs. Moreover, overall emergency procurement setting and its effects on competition vary across countries regardless of how intensely the pandemic hit, indicating an institutional context for the increased discretion effects on procurement outcome.

A restricted subset selection procedure for selecting the largest normal mean under heteroscedasticity

This article considers the goal of selecting the population with the largest mean among k normal populations when variances are not known. We propose a Stein-type two-sample procedure, denoted by for selecting a nonempty random-size subset of size at most m () that contains the population associated with the largest mean, with a guaranteed minimum probability whenever the distance between the largest mean and the second largest mean is at least where m, and are specified in advance of the experiment. The probability of a correct selection and the expected subset size of are derived. Critical values/procedure parameters that are required for certain k, m, and are obtained by solving simultaneous integral equations and are presented in tables.

Adult/child ratio and group size in early childhood education or care to promote the development of children aged 0-5 years: A systematic review.

Adult/child ratio and group size in early childhood education or care to promote the development of children aged 0-5 years: A systematic review.

Genetic parameters for repeatedly recorded enteric methane concentrations of dairy cows

Animal breeding techniques offer potential to reduce enteric emissions of ruminants to lower the environmental impact of dairy farming. The aim of this study was to estimate the heritability and repeatability of methane (CH4) concentrations, using the largest data set from long-term repeatedly recorded CH4 on cows to date, and to evaluate (1) the accuracy of breeding values for different CH4 traits, including using visits or weekly means, and (2) recording strategies (with varying numbers of records and recorded daughters per sire). The data comprised of long-term recording of CH4 and carbon dioxide (CO2), from 1,746 Holstein Friesian cows, on 14 commercial dairy farms throughout the Netherlands. Emissions were recorded in 10- to 35-s intervals, between 64 and 436 d, depending on farms. From each robot visit, CH4 and CO2 concentrations were summarized into various traits, averaged per visit and per week: mean, median, mean log, and mean CH4/CO2 ratio. Genetic parameters were estimated with animal repeatability models, using a restricted maximum likelihood procedure, and a relationship matrix based on genotypes and pedigree. The heritability was equal for mean and median CH4 per visit (0.13) but lower for logCH4 and CH4/CO2 (0.07 and 0.01, respectively). Phenotypic and genetic correlations were high (≥0.78) between the CH4 traits, apart from the genetic correlations with the CH4/CO2 trait, which were negative. To achieve a minimum reliability of 50% for the estimated breeding value of a bull, 25 records on mean CH4, measured on 10 different daughters, were sufficient. Although the heritability and repeatability were higher for weekly (0.32 and 0.68, respectively) than for visit mean CH4 (0.13 and 0.30, respectively), the reliabilities of estimated breeding values from visit or weekly means were equal; thus, we found no advantage in averaging records to weekly means for genetic evaluations.

Genetic and phenotypic correlations between backfat thickness and weight at 28weeks of age, and reproductive performance in primiparous Landrace sows raised under tropical conditions.

Backfat thickness could reflect the energy reserve of female pigs that is required for their reproductivity, especially gilts that might be selected as replacements. In this study, genetic and phenotypic correlations between backfat thickness (BF) and body weight (BW) at 28weeks of age, and reproduction traits were estimated. They were considered for the possibility of using BF at the pre-selective stage as an early indicator of sow's reproduction potential. Pedigree information, BF and BW at 28weeks of age, age at first farrowing (AFF), transformed proportion of piglet loss at birth (tPL), and transformed weaning to first service interval (tWSI) of 806 primiparous Landrace sows were used to estimate the variance components by a restricted maximum likelihood procedure with an average information algorithm for multivariate analysis. The genetic correlation between BF and BW was 0.70 ± 0.13. Both BF and BW had a negative genetic correlation with AFF but not with tWSI. Genetic correlation estimates between tPL and other traits were unclear due to high standard error. The genetic correlation between AFF and tWSI was 0.78 ± 0.36. There were 19.35% of sires, 26.34% of dams, and 25.81% of sows that had preferable estimated breeding values for BF, BW, AFF, and WSI. These values indicated the feasibility of using selection index to improve BF and BW at the pre-selective stage and reduce AFF and tWSI of replacement gilt simultaneously. The estimation of genetic correlation between PL and other traits warrants further study in larger populations.

Differential effects of time-restricted feeding on circadian locomotor activity, food intake and body weight gain in BALB/cJ and C57BL/6J mice

ABSTRACT Time-restricted feeding is used to study the food-entrainable oscillator in mammals, yet there is considerable inconsistency in procedures for imposing restrictions. Additionally, the majority of rodent studies being used to model this strategy employ C57BL/6 J laboratory mice, which likely do not represent the diversity in human circadian responses. We compared effects of time-restricted feeding (TRF) and periodic phase shifts of the light-dark cycle on food intake, weight maintenance and distribution of locomotor activity in TRF and ad-lib fed C57BL/6 J and BALB/cJ mice. Imposing TRF initially produced significantly greater weight loss in BALB/cJ mice, the degree of which depended on the procedure employed. TRF yielded caloric restriction throughout the duration of the experiment in BALB/cJ but not C57BL/6 J mice, and resulted in significantly greater re-distribution of daily locomotor activity relative to the light-dark cycle in BALB/cJ mice. Food intake and weight gain in BALB/cJ mice also varied with time of feeding. These findings emphasize that the same restricted feeding procedure can produce substantially different physiological and behavioral outcomes that must be considered when developing studies on time-restricted feeding in mice.

A roadmap to using randomization in clinical trials

BackgroundRandomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available. The goal of this paper is to present a systematic roadmap for the choice and application of a restricted randomization procedure in a clinical trial.MethodsWe survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice.ResultsRestricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size.ConclusionsThe choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators.