Sample size justifications in Gait & Posture

BACKGROUND: Context regarding how researchers determine the sample size of their experiments is important for interpreting the results and determining their value and meaning. Between 2018 and 2019, the journal Gait & Posture introduced a requirement for sample size justification in their author guidelines. RESEARCH QUESTION: How frequently and in what ways are sample sizes justified in Gait & Posture research articles and was the inclusion of a guideline requiring sample size justification associated with a change in practice? METHODS: The guideline was not in place prior to May 2018 and was in place from 25th July 2019. All articles in the three most recent volumes of the journal (84-86) and the three most recent, pre-guideline volumes (60-62) at time of preregistration were included in this analysis. This provided an initial sample of 324 articles (176 pre-guideline and 148 post-guideline). Articles were screened by two authors to extract author data, article metadata and sample size justification data. Specifically, screeners identified if (yes or no) and how sample sizes were justified. Six potential justification types (Measure Entire Population, Resource Constraints, Accuracy, A priori Power Analysis, Heuristics, No Justification) and an additional option of Other/Unsure/Unclear were used. RESULTS: In most cases, authors of Gait & Posture articles did not provide a justification for their study's sample size. The inclusion of the guideline was associated with a modest increase in the percentage of articles providing a justification (16.6-28.1%). A priori power calculations were the dominant type of justification, but many were not reported in enough detail to allow replication. SIGNIFICANCE: Gait & Posture researchers should be more transparent in how they determine their sample sizes and carefully consider if they are suitable. Editors and journals may consider adding a similar guideline as a low-resource way to improve sample size justification reporting

Introduction of biodiesel to rail transport: Lessons from the road sector

Biodiesel is a potentially low-carbon, renewable alternative fuel to diesel, sharing similar chemical and physical properties to diesel. There have been significant efforts in introducing primarily bioethanol and some biodiesel to the road transport sector, with varying levels of success. However, the rail sector has not seen as large an effort in introducing biodiesel. This paper summarizes the literature on the introduction of biodiesel (bioethanol was a relevant fuel) in order to learn lessons, which can be applied to the rail transport sector. A decision-making framework PESTLE (Political/Policies, Economic, Social, Technological, Legal, and Environmental) is used to analyze these lessons, and their relevance (or not) to the rail sector. While introduction of biodiesel in the rail sector has some inherent advantages, such as fewer refueling points, customers and manufacturers compared to the road sector, it also faces some challenges, especially in the context of the longer life of locomotives, making fleet turnover and potential transition to 100% biodiesel slow. Additionally, maintenance costs are still uncertain

Organizing Effects of Sex Steroids on Brain Aromatase Activity in Quail

Preoptic/hypothalamic aromatase activity (AA) is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1) brain sites where AA is sexually differentiated and (2) whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST) followed by the medial preoptic nucleus (POM) and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole) on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

"Girls can't play": The effects of stereotype threat on females' gaming performance

The current study examined the impact of stereotype threat on female online gamers' performance and further examined whether manipulating the availability of multiple social identities effectively eliminated these performance decrements. Further, participants' implicit attitudes towards female online gamers were assessed. Eighty-one participants (60 female) were assigned to one of four experimental conditions: 1), stereotype threat, 2), multiple social identities, 3), female control, and 4), male control. They completed an Implicit Association Test and a gaming task. The number of coins collected in a 5-min time period provided a measure of gameplay performance. Results indicated that stereotype threatened females underperformed on the gaming task relative to males in the control condition. The intervention of multiple social identities successfully protected females' gameplay performance from stereotype threat. Additionally, differences were found between conditions in implicit attitudes pertaining to gender-gaming competence. This research highlights the harmful effects of negative stereotypes on females' gaming performance, and suggests that these decrements may be eliminated when females identify with an alternative positive social identity

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO’s MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest