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

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Gender-identity typologies are related to gender-typing, friendships, and social-emotional adjustment in Dutch emerging adults

The current study examined emerging adults’ gender identity and its link with several gender-related and social outcomes, by using a novel dual-identity approach that was originally developed in children. Dutch emerging adults between 18 and 25 years old (N = 318, Mage = 21.73, SD = 2.02; 51% female) indicated their similarity to the own-gender group and the other-gender group to assess gender identity. They completed questionnaires assessing gender-typed behavior (internalized sexualization, toughness, emotional stoicism) and attitudes (i.e., sexism); friendship efficacy and ability; and social-emotional adjustment. Cluster analysis on the gender-identity items revealed four gender-identity types: (a) feeling similar to one’s own gender, but not to the other gender (Own-GS); (b) feeling similar to both one’s own and the other gender (Both-GS); (c) feeling dissimilar to one’s own gender (Low-Own-GS); and (d) feeling similar to neither gender (Low-GS). Own-GS and Low-GS adults were most gender-typed in their behavior and showed sexist attitudes. Both-GS adults felt efficacious and were highly able to relate to both genders, whereas the other groups felt efficacious and were able to relate to only one gender (Own-GS, Low-Own-GS), or to neither gender (Low-GS). Low-Own-GS and Low-GS were least well-adjusted social-emotionally. Findings suggest that identifying with one’s own gender is helpful for certain aspects of social-emotional adjustment but that also identifying with the other gender provides the advantage of flexible social and interpersonal skills and egalitarian gender attitudes.</p

Gender-identity typologies are related to gender-typing, friendships, and social-emotional adjustment in Dutch emerging adults

The current study examined emerging adults’ gender identity and its link with several gender-related and social outcomes, by using a novel dual-identity approach that was originally developed in children. Dutch emerging adults between 18 and 25 years old (N = 318, Mage = 21.73, SD = 2.02; 51% female) indicated their similarity to the own-gender group and the other-gender group to assess gender identity. They completed questionnaires assessing gender-typed behavior (internalized sexualization, toughness, emotional stoicism) and attitudes (i.e., sexism); friendship efficacy and ability; and social-emotional adjustment. Cluster analysis on the gender-identity items revealed four gender-identity types: (a) feeling similar to one’s own gender, but not to the other gender (Own-GS); (b) feeling similar to both one’s own and the other gender (Both-GS); (c) feeling dissimilar to one’s own gender (Low-Own-GS); and (d) feeling similar to neither gender (Low-GS). Own-GS and Low-GS adults were most gender-typed in their behavior and showed sexist attitudes. Both-GS adults felt efficacious and were highly able to relate to both genders, whereas the other groups felt efficacious and were able to relate to only one gender (Own-GS, Low-Own-GS), or to neither gender (Low-GS). Low-Own-GS and Low-GS were least well-adjusted social-emotionally. Findings suggest that identifying with one’s own gender is helpful for certain aspects of social-emotional adjustment but that also identifying with the other gender provides the advantage of flexible social and interpersonal skills and egalitarian gender attitudes.</p

Gender-identity typologies are related to gender-typing, friendships, and social-emotional adjustment in Dutch emerging adults

The current study examined emerging adults’ gender identity and its link with several gender-related and social outcomes, by using a novel dual-identity approach that was originally developed in children. Dutch emerging adults between 18 and 25 years old (N = 318, Mage = 21.73, SD = 2.02; 51% female) indicated their similarity to the own-gender group and the other-gender group to assess gender identity. They completed questionnaires assessing gender-typed behavior (internalized sexualization, toughness, emotional stoicism) and attitudes (i.e., sexism); friendship efficacy and ability; and social-emotional adjustment. Cluster analysis on the gender-identity items revealed four gender-identity types: (a) feeling similar to one’s own gender, but not to the other gender (Own-GS); (b) feeling similar to both one’s own and the other gender (Both-GS); (c) feeling dissimilar to one’s own gender (Low-Own-GS); and (d) feeling similar to neither gender (Low-GS). Own-GS and Low-GS adults were most gender-typed in their behavior and showed sexist attitudes. Both-GS adults felt efficacious and were highly able to relate to both genders, whereas the other groups felt efficacious and were able to relate to only one gender (Own-GS, Low-Own-GS), or to neither gender (Low-GS). Low-Own-GS and Low-GS were least well-adjusted social-emotionally. Findings suggest that identifying with one’s own gender is helpful for certain aspects of social-emotional adjustment but that also identifying with the other gender provides the advantage of flexible social and interpersonal skills and egalitarian gender attitudes

Exploring dual gender typicality among young adults in the United States

The goal of the current study was to better understand the development of gender typicality in young adulthood by applying the dual-identity approach to gender typicality, previously developed with children, to a university sample. Participants (n = 215, Mage = 20.20 years; 62% female) were asked to rate their perceived similarity to both own- and other-gender peers. They also completed questionnaires assessing sexist attitudes, internalized sexualization (females), adherence to male-typed behaviors in the context of interpersonal relationships (males; adherence to physical toughness and restrictive emotional expressivity), gender-based relationship efficacy, friendships, self-esteem, social self-efficacy, and social anxiety. Results indicated that self-perceived gender typicality involves comparisons to both gender groups, and that meaningful typologies can be created based on similarity to own- and other-gender groups. As with children, results indicated that identifying with one’s own gender was advantageous in terms of low social anxiety and relationships with own-gender peers. For adults who identified with both own- and other-gender peers, we identified additional social benefits (i.e., efficacy and friendships with other-gender peers). Further, we identified a downside to own-gender typicality: individuals who identified only with their own gender had more sexist attitudes than those who identified with the other gender. Findings support the viability of the dual-identity approach in young adults, and have implications for researchers assessing gender typicality across development.</p

Exploring dual gender typicality among young adults in the United States

The goal of the current study was to better understand the development of gender typicality in young adulthood by applying the dual-identity approach to gender typicality, previously developed with children, to a university sample. Participants (n = 215, Mage = 20.20 years; 62% female) were asked to rate their perceived similarity to both own- and other-gender peers. They also completed questionnaires assessing sexist attitudes, internalized sexualization (females), adherence to male-typed behaviors in the context of interpersonal relationships (males; adherence to physical toughness and restrictive emotional expressivity), gender-based relationship efficacy, friendships, self-esteem, social self-efficacy, and social anxiety. Results indicated that self-perceived gender typicality involves comparisons to both gender groups, and that meaningful typologies can be created based on similarity to own- and other-gender groups. As with children, results indicated that identifying with one’s own gender was advantageous in terms of low social anxiety and relationships with own-gender peers. For adults who identified with both own- and other-gender peers, we identified additional social benefits (i.e., efficacy and friendships with other-gender peers). Further, we identified a downside to own-gender typicality: individuals who identified only with their own gender had more sexist attitudes than those who identified with the other gender. Findings support the viability of the dual-identity approach in young adults, and have implications for researchers assessing gender typicality across development.</p

A Dual Identity Approach for Conceptualizing and Measuring Children's Gender Identity

The goal was to test a new dual identity perspective on gender identity by asking children (n = 467) in three grades (Mage = 5.7, 7.6, 9.5) to consider the relation of the self to both boys and girls. This change shifted the conceptualization of gender identity from one to two dimensions, provided insights into the meaning and measurement of gender identity, and allowed for revisiting ideas about the roles of gender identity in adjustment. Using a graphical measure to allow assessment of identity in young children and cluster analyses to determine types of identity, it was found that individual and developmental differences in how similar children feel to both genders, and these variations matter for many important personal and social outcomes.</p

A Dual Identity Approach for Conceptualizing and Measuring Children's Gender Identity

The goal was to test a new dual identity perspective on gender identity by asking children (n = 467) in three grades (Mage = 5.7, 7.6, 9.5) to consider the relation of the self to both boys and girls. This change shifted the conceptualization of gender identity from one to two dimensions, provided insights into the meaning and measurement of gender identity, and allowed for revisiting ideas about the roles of gender identity in adjustment. Using a graphical measure to allow assessment of identity in young children and cluster analyses to determine types of identity, it was found that individual and developmental differences in how similar children feel to both genders, and these variations matter for many important personal and social outcomes.</p