How robust is the evidence of an emerging or increasing female excess in physical morbidity between childhood and adolescence? Results of a systematic literature review and meta-analyses

For asthma and psychological morbidity, it is well established that higher prevalence among males in childhood is replaced by higher prevalence among females by adolescence. This review investigates whether there is evidence for a similar emerging female ‘excess’ in relation to a broad range of physical morbidity measures. Establishing whether this pattern is generalised or health outcome-specific will further understandings of the aetiology of gender differences in health. Databases (Medline; Embase; CINAHL; PsycINFO; ERIC) were searched for English language studies (published 1992–2010) presenting physical morbidity prevalence data for males and females, for at least two age-bands within the age-range 4–17 years. A three-stage screening process (initial sifting; detailed inspection; extraction of full papers), was followed by study quality appraisals. Of 11 245 identified studies, 41 met the inclusion criteria. Most (n = 31) presented self-report survey data (five longitudinal, 26 cross-sectional); 10 presented routinely collected data (GP/hospital statistics). Extracted data, supplemented by additional data obtained from authors of the included studies, were used to calculate odds ratios of a female excess, or female:male incident rate ratios as appropriate. To test whether these changed with age, the values were logged and regressed on age in random effects meta-regressions. These showed strongest evidence of an emerging/increasing female excess for self-reported measures of headache, abdominal pain, tiredness, migraine and self-assessed health. Type 1 diabetes and epilepsy, based on routinely collected data, did not show a significant emerging/increasing female excess. For most physical morbidity measures reviewed, the evidence broadly points towards an emerging/increasing female excess during the transition to adolescence, although results varied by morbidity measure and study design, and suggest that this may occur at a younger age than previously thought

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Spectroscopy of 50^{50}Sc and ab initio calculations of B(M3)B(M3) strengths

The GRIFFIN spectrometer at TRIUMF-ISAC has been used to study excited states and transitions in $^{50}$Sc following the $\beta$-decay of $^{50}$Ca. Branching ratios were determined from the measured $\gamma$-ray intensities, and angular correlations of $\gamma$ rays have been used to firmly assign the spins of excited states. The presence of an isomeric state that decays by an $M3$ transition with a $B(M3)$ strength of 13.6(7)\,W.u. has been confirmed. We compare with the first {\it ab initio} calculations of $B(M3$) strengths in light and medium-mass nuclei from the valence-space in-medium similarity renormalization group approach, using consistently derived effective Hamiltonians and $M3$ operator. The experimental data are well reproduced for isoscalar $M3$ transitions when using bare $g$-factors, but the strength of isovector $M3$ transitions are found to be underestimated by an order of magnitude

Climate Change and Malaria in Canada: A Systems Approach

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change

Sex-dependent influence of endogenous estrogen in pulmonary hypertension

Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH; the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of gender on pulmonary expression of aromatase in these models and in lungs from PAH patients. Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was due to reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor alpha also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased BMPR2 and Id1 expression compared to male. Anastrozole treatment reversed the impaired BMPR2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared to male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential

Additive and non-additive genetic variance in juvenile Sitka spruce (Picea sitchensis Bong. Carr)

Many quantitative genetic models assume that all genetic variation is additive because of a lack of data with sufficient structure and quality to determine the relative contribution of additive and non-additive variation. Here the fractions of additive (fa) and non-additive (fd) genetic variation were estimated in Sitka spruce for height, bud burst and pilodyn penetration depth. Approximately 1500 offspring were produced in each of three sib families and clonally replicated across three geographically diverse sites. Genotypes from 1525 offspring from all three families were obtained by RADseq, followed by imputation using 1630 loci segregating in all families and mapped using the newly developed linkage map of Sitka spruce. The analyses employed a new approach for estimating fa and fd, which combined all available genotypic and phenotypic data with spatial modelling for each trait and site. The consensus estimate for fa increased with age for height from 0.58 at 2 years to 0.75 at 11 years, with only small overlap in 95% support intervals (I95). The estimated fa for bud burst was 0.83 (I95=[0.78, 0.90]) and 0.84 (I95=[0.77, 0.92]) for pilodyn depth. Overall, there was no evidence of family heterogeneity for height or bud burst, or site heterogeneity for pilodyn depth, and no evidence of inbreeding depression associated with genomic homozygosity, expected if dominance variance was the major component of non-additive variance. The results offer no support for the development of sublines for crossing within the species. The models give new opportunities to assess more accurately the scale of non-additive variation

Shape Changes of Self-Assembled Actin Bilayer Composite Membranes

We report the self-assembly of thin actin shells beneath the membranes of giant vesicles. Ion-carrier mediated influx of Mg2+ induces actin polymerization in the initially spherical vesicles. Buckling of the vesicles and the formation of blisters after thermally induced bilayer expansion is demonstrated. Bilayer flickering is dominated by tension generated by its coupling to the actin cortex. Quantitative flicker analysis suggests the bilayer and the actin cortex are separated by 0.4 \mum to 0.5 \mum due to undulation forces.Comment: pdf-file, has been accepted by PR