The Trouble with Sex Differences

Sex differences in the brain are real and clinically important but often grossly distorted in popular discourse. Considering the public's deep fascination with sex difference research and its impact on issues from mental health to education and workplace equity, neuroscientists should pay greater heed to its misappropriation and to studying how gender enculturation shapes neural function

How global changes impact water resources in a southern coastal metropolis? Case of Recife (Brazil)

International audienceThe Recife Metropolitan Region is a hot spot illustrating the problems of southern countries on water issues where water resources are threatened both for quantity and quality in the context of global changes. Based on a transdisciplinary approach, the purpose of the study was to assess the impact of human activities on coastal aquifers, through the analysis of pressure on groundwater resources and their social and structural reasons, the identification of sources and mechanisms of groundwater quality degradation, and the evaluation of the impacts of global changes on water resources at the regional level. The methodology was based on a multi-isotopic fingerprinting of groundwater and surface water, on gas analyses, and on sociological and ethnographic investigations including ethno-photography to characterize the daily life of the Recife inhabitants facing the lack of water or its poor quality. The results revisit the aquifer system functioning. In the deep aquifers, the groundwater displays a residence time over 10 000 y with a residual salinity inherited from the Pleistocene marine transgressions. Their recharge is very limited resulting in large water level decrease. Inversed flow directions due to overexploitation favour leakage from the surficial contaminated aquifers. The access to water and its social perception vary according to the social environment and to the residence location of individuals. Access to water is more a political problem than a technical one. The public authorities tend to deny the difficulties of poor people, especially in times of drought. The discredit of the water and sanitation public actors, and political and institutional rivalries and fragmentation are obstacles to technical solutions implementation. Integrated water management is urgently needed knowing that local climatic scenarios predict a reduction of rainfall volume of 20% together with a sea level increase of 18-59 cm by 2100

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Remembering the null hypothesis when searching for brain sex differences

Abstract Human brain sex differences have fascinated scholars for centuries and become a key focus of neuroscientists since the dawn of MRI. We recently published a major review in Neuroscience and Biobehavioral Reviews showing that most male–female brain differences in humans are small and few have been reliably replicated. Although widely cited, this work was the target of a critical Commentary by DeCasien et al. (Biol Sex Differ 13:43, 2022). In this response, I update our findings and confirm the small effect sizes and pronounced scatter across recent large neuroimaging studies of human sex/gender difference. Based on the sum of data, neuroscientists would be well-advised to take the null hypothesis seriously: that men and women’s brains are fundamentally similar, or “monomorphic”. This perspective has important implications for how we study the genesis of behavioral and neuropsychiatric gender disparities

How hype and hyperbole distort the neuroscience of sex differences.

Sex/gender differences in the human brain attract attention far beyond the neuroscience community. Given the interest of nonspecialists, it is important that researchers studying human female-male brain difference assume greater responsibility for the accurate communication of their findings

Dump the “dimorphism”: Comprehensive synthesis of human brain studies reveals few male-female differences beyond size

With the explosion of neuroimaging, differences between male and female brains have been exhaustively analyzed. Here we synthesize three decades of human MRI and postmortem data, emphasizing meta-analyses and other large studies, which collectively reveal few reliable sex/gender differences and a history of unreplicated claims. Males’ brains are larger than females’ from birth, stabilizing around 11% in adults. This size difference accounts for other reproducible findings: higher white/gray matter ratio, intra- versus interhemispheric connectivity, and regional cortical and subcortical volumes in males. But when structural and lateralization differences are present independent of size, sex/gender explains only about 1% of total variance. Connectome differences and multivariate sex/gender prediction are largely based on brain size, and perform poorly across diverse populations. Task-based fMRI has especially failed to find reproducible activation differences between men and women in verbal, spatial or emotion processing due to high rates of false discovery. Overall, male/female brain differences appear trivial and population-specific. The human brain is not “sexually dimorphic.

Why and How to Account for Sex and Gender in Brain and Behavioral Research.

Long overlooked in neuroscience research, sex and gender are increasingly included as key variables potentially impacting all levels of neurobehavioral analysis. Still, many neuroscientists do not understand the difference between the terms sex and gender, the complexity and nuance of each, or how to best include them as variables in research designs. This TechSights article outlines rationales for considering the influence of sex and gender across taxa, and provides technical guidance for strengthening the rigor and reproducibility of such analyses. This guidance includes the use of appropriate statistical methods for comparing groups as well as controls for key covariates of sex (e.g., total intracranial volume) and gender (e.g., income, caregiver stress, bias). We also recommend approaches for interpreting and communicating sex- and gender-related findings about the brain, which have often been misconstrued by neuroscientists and the lay public alike