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The success of the immune response is finely balanced between, on the one hand, the need to engage vigorously with, and clear, certain pathogens; and, on the other, the requirement to minimize immunopathology and autoimmunity. Distinct immune strategies to achieve this balance have evolved in females and males and also in infancy through to adulthood. Sex differences in outcome from a range of infectious diseases can be identified from as early as fetal life, such as in congenital cytomegalovirus infection. The impact of sex hormones on the T-helper 1/T-helper 2 cytokine balance has been proposed to explain the higher severity of most infectious diseases in males. In the minority where greater morbidity and mortality is observed in females, this is hypothesized to arise because of greater immunopathology and/or autoimmunity. However, a number of unexplained exceptions to this rule are described. Studies that have actually measured the sex differences in children in the immune responses to infectious diseases and that would further test these hypotheses, are relatively scarce.

Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8—22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18-74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.

Much has been written in the past two decades about women in academic science careers, but this literature is contradictory. Many analyses have revealed a level playing field, with men and women faring equally, whereas other analyses have suggested numerous areas in which the playing field is not level. The only widely-agreed-upon conclusion is that women are underrepresented in college majors, graduate school programs, and the professoriate in those fields that are the most mathematically intensive, such as geoscience, engineering, economics, mathematics/computer science, and the physical sciences. In other scientific fields (psychology, life science, social science), women are found in much higher percentages. In this monograph, we undertake extensive life-course analyses comparing the trajectories of women and men in math-intensive fields with those of their counterparts in non-math-intensive fields in which women are close to parity with or even exceed the number of men. We begin by examining early-childhood differences in spatial processing and follow this through quantitative performance in middle childhood and adolescence, including high school coursework. We then focus on the transition of the sexes from high school to college major, then to graduate school, and, finally, to careers in academic science. The results of our myriad analyses reveal that early sex differences in spatial and mathematical reasoning need not stem from biological bases, that the gap between average female and male math ability is narrowing (suggesting strong environmental influences), and that sex differences in math ability at the right tail show variation over time and across nationalities, ethnicities, and other factors, indicating that the ratio of males to females at the right tail can and does change. We find that gender differences in attitudes toward and expectations about math careers and ability (controlling for actual ability) are evident by kindergarten and increase thereafter, leading to lower female propensities to major in math-intensive subjects in college but higher female propensities to major in non-math-intensive sciences, with overall science, technology, engineering, and mathematics (STEM) majors at 50% female for more than a decade. Post-college, although men with majors in math-intensive subjects have historically chosen and completed PhDs in these fields more often than women, the gap has recently narrowed by two thirds; among non-math-intensive STEM majors, women are more likely than men to go into health and other people-related occupations instead of pursuing PhDs. Importantly, of those who obtain doctorates in math-intensive fields, men and women entering the professoriate have equivalent access to tenure-track academic jobs in science, and they persist and are remunerated at comparable rates—with some caveats that we discuss. The transition from graduate programs to assistant professorships shows more pipeline leakage in the fields in which women are already very prevalent (psychology, life science, social science) than in the math-intensive fields in which they are underrepresented but in which the number of females holding assistant professorships is at least commensurate with (if not greater than) that of males. That is, invitations to interview for tenure-track positions in math-intensive fields—as well as actual employment offers—reveal that female PhD applicants fare at least as well as their male counterparts in math-intensive fields. Along these same lines, our analyses reveal that manuscript reviewing and grant funding are gender neutral: Male and female authors and principal investigators are equally likely to have their manuscripts accepted by journal editors and their grants funded, with only very occasional exceptions. There are no compelling sex differences in hours worked or average citations per publication, but there is an overall male advantage in productivity. We attempt to reconcile these results amid the disparate claims made regarding their causes, examining sex differences in citations, hours worked, and interests. We conclude by suggesting that although in the past, gender discrimination was an important cause of women's underrepresentation in scientific academic careers, this claim has continued to be invoked after it has ceased being a valid cause of women's underrepresentation in math-intensive fields. Consequently, current barriers to women's full participation in mathematically intensive academic science fields are rooted in pre-college factors and the subsequent likelihood of majoring in these fields, and future research should focus on these barriers rather than misdirecting attention toward historical barriers that no longer account for women's underrepresentation in academic science.

Explanations for women's underrepresentation in math-intensive fields of science often focus on sex discrimination in grant and manuscript reviewing, interviewing, and hiring. Claims that women scientists suffer discrimination in these arenas rest on a set of studies undergirding policies and programs aimed at remediation. More recent and robust empiricism, however, fails to support assertions of discrimination in these domains. To better understand women's underrepresentation in math-intensive fields and its causes, we reprise claims of discrimination and their evidentiary bases. Based on a review of the past 20 y of data, we suggest that some of these claims are no longer valid and, if uncritically accepted as current causes of women's lack of progress, can delay or prevent understanding of contemporary determinants of women's underrepresentation. We conclude that differential gendered outcomes in the real world result from differences in resources attributable to choices, whether free or constrained, and that such choices could be influenced and better informed through education if resources were so directed. Thus, the ongoing focus on sex discrimination in reviewing, interviewing, and hiring represents costly, misplaced effort: Society is engaged in the present in solving problems of the past, rather than in addressing meaningful limitations deterring women's participation in science, technology, engineering, and mathematics careers today. Addressing today's causes of underrepresentation requires focusing on education and policy changes that will make institutions responsive to differing biological realities of the sexes. Finally, we suggest potential avenues of intervention to increase gender fairness that accord with current, as opposed to historical, findings.

Biological (ie, sex) differences as well as cultural (ie, gender) norms influence the acceptance and efficacy of vaccines for males and females. These differences are often overlooked in the design and implementation of vaccination strategies. Using seasonal and pandemic influenza vaccines, we document profound differences between the sexes in the acceptance, correlates of protection, and adverse reactions following vaccination in both young and older adults. Females develop higher antibody responses, experience more adverse reactions to influenza vaccines, and show greater vaccine efficacy than males. Despite greater vaccine efficacy in females, both young and older females are often less likely to accept influenza vaccines than their male counterparts. Identification of the biological mechanisms, including the hormones and genes, that underlie differential responses to vaccination is necessary. We propose that vaccines should be matched to an individual's biological sex, which could involve systematically tailoring diverse types of FDA-approved influenza vaccines separately for males and females. One goal for vaccines designed to protect against influenza and even other infectious diseases should be to increase the correlates of protection in males and reduce adverse reactions in females in an effort to increase acceptance and vaccine-induced protection in both sexes.

Two cohorts of intellectually talented 13-year-olds were identified in the 1970s (1972–1974 and 1976–1978) as being in the top 1% of mathematical reasoning ability (1,037 males, 613 females). About four decades later, data on their careers, accomplishments, psychological well-being, families, and life preferences and priorities were collected. Their accomplishments far exceeded base-rate expectations: Across the two cohorts, 4.1% had earned tenure at a major research university, 2.3% were top executives at \"name brand\" or Fortune 500 companies, and 2.4% were attorneys at major firms or organizations; participants had published 85 books and 7,572 refereed articles, secured 681 patents, and amassed $358 million in grants. For both males and females, mathematical precocity early in life predicts later creative contributions and leadership in critical occupational roles. On average, males had incomes much greater than their spouses', whereas females had incomes slightly lower than their spouses'. Salient sex differences that paralleled the differential career outcomes of the male and female participants were found in lifestyle preferences and priorities and in time allocation.

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus–subgenual cingulate rs-FC in both adolescent females and males and lower amygdala–subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain’s fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto–amygdala and –hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea.