Site and gender specificity of inheritance of bone mineral density

Differences in genetic control of BMD by skeletal sites and genders were examined by complex segregation analysis in 816 members of 147 families with probands with extreme low BMD. Spine BMD correlated more strongly in male-male comparisons and hip BMD in female-female comparisons, consistent with gender- and site-specificity of BMD heritability. Introduction: Evidence from studies in animals and humans suggests that the genetic control of bone mineral density (BMD) may differ at different skeletal sites and between genders. This question has important implications for the design and interpretation of genetic studies of osteoporosis. Methods: We examined the genetic profile of 147 families with 816 individuals recruited through probands with extreme low BMD (T-score < −2.5, Z-score < −2.0). Complex segregation analysis was performed using the Pedigree Analysis Package. BMD was measured by DXA at both lumbar spine (L1-L4) and femoral neck. Results: Complex segregation analysis excluded purely monogenic and environmental models of segregation of lumbar spine and femoral neck BMD in these families. Pure polygenic models were excluded at the lumbar spine when menopausal status was considered as a covariate, but not at the femoral neck. Mendelian models with a residual polygenic component were not excluded. These models were consistent with the presence of a rare Mendelian genotype of prevalence 3–19 %, causing high BMD at the hip and spine in these families, with additional polygenic effects. Total heritability range at the lumbar spine was 61–67 % and at the femoral neck was 44–67 %. Significant differences in correlation of femoral neck and lumbar spine BMD were observed between male and female relative pairs, with male-male comparisons exhibiting stronger lumbar spine BMD correlation than femoral neck, and female-female comparisons having greater femoral neck BMD correlation than lumbar spine. These findings remained true for parent-offspring correlations when menopausal status was taken into account. The recurrence risk ratio for siblings of probands of a Z-score < −2.0 was 5.4 at the lumbar spine and 5.9 at the femoral neck. Conclusions: These findings support gender- and site-specificity of the inheritance of BMD. These results should be considered in the design and interpretation of genetic studies of osteoporosis.

We need to support paedophiles to prevent child sex offending

The sexual abuse of children is, understandably, a key concern for the public. Child sexual abuse can cause long-lasting harms for victims, ranging from relationship difficulties to eating disorders. But misperceptions about those who perpetrate it abound in public debate. Although the terms “paedophile” and “child sex offender” are often used interchangeably, the two are distinct. Paedophiles are sexually attracted to young children. They have either acted on this attraction or fear they might. But not all paedophiles act on their attraction – and this is where support services can help reducing offending. Conversely, not everyone who offends sexually against a child is a paedophile. Some may have a sexual interest in and/or offend against both children and adults. Others do not have a sexual attraction to children but instead act opportunistically...

Book Review "Selling sex: a hidden history of prostitution", R. Frances, UNSW Press, Sydney, 2007

In the opening pages of Selling Sex we are introduced to 'Joy', a statue of a young female sex worker which stood in East Sydney for eighteen months during 1995- 1997. Following complaints by local residents, the statue was removed from public view and returned to its owner. Evidently, Joy was considered a reminder of the community's 'bad old days', when it was better known for prostitution than restaurants. In a nation in which almost every sizable community has proudly erected monuments to military men, the removal of Joy reveals much about labour and gender relations in Australia. For Frances, the removal of Joy is symbolic, our historical treatment of sex workers having parallels with our treatment of the convicts. This work sets out to give these women (male prostitutes do not figure in this history) a voice and break with the stereotypes of 'abandoned whores' or 'sad victims'. It also sets out to place the sex industry in the broader national and international context in which it has historically operated...

Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were: (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10), and; (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

Distribution of ocular biometry in 7- and 14-year-old Chinese children

Purpose: To describe distributions of ocular biometry and their associations with refraction in 7- and 14-year-old children in urban areas of Anyang, central China. Methods: A total of 2271 grade 1 students aged 7.1 ± 0.4 years and 1786 grade 8 students aged 13.7 ± 0.5 years were measured with ocular biometry and cycloplegic refraction. A parental myopia questionnaire was administered to parents. Results: Mean axial length, anterior chamber depth, lens thickness, central corneal thickness, corneal diameter, corneal radius of curvature, axial length/corneal radius of curvature ratio, and spherical equivalent refraction were 22.72 ± 0.76 mm, 2.89 ± 0.24 mm, 3.61 ± 0.19 mm, 540.5 ± 31 μm, 12.06 ± 0.44 mm, 7.80 ± 0.25 mm, 2.91 ± 0.08, and +0.95 ± 1.05 diopters (D), respectively, in 7-year-old children. They were 24.39 ± 1.13 mm, 3.42 ± 0.41 mm, 3.18 ± 0.24 mm, 548.9 ± 33 μm, 12.03 ± 0.43 mm, 7.80 ± 0.26 mm, 3.13 ± 0.14, and −2.06 ± 2.20 D, respectively, in 14-year-old children. Compared with 7-year-old children, the older group had significantly more myopia (−3.0 D), longer axial length (1.7 mm), deeper anterior chamber depth (0.3 mm), thinner lens thickness (−0.2 mm), thicker central corneal thickness (10 μm), and greater axial length/corneal radius of curvature ratio (0.22) (all p < 0.001), as well as smaller corneal diameter (−0.03 mm, p = 0.02) and similar corneal radius of curvature. Sex differences were similar in both age groups, with boys having longer axial length (0.5 mm), deeper anterior chamber depth (0.1 mm), shorter lens thickness (0.03 mm), greater central corneal thickness (5 μm), greater corneal diameter (0.15 mm), and greater corneal radius of curvature (0.14 mm) than girls (all p < 0.01). The most important variables related to spherical equivalent refraction were vitreous length, corneal radius of curvature, and lens thickness. Conclusions: The 14-year-old group had larger parameter dimensions than the 7-year-old group except for corneal radius of curvature (unchanged) and lens thickness and corneal diameter (both smaller). Boys had large parameter dimensions than girls except for lens thickness (smaller). Axial length, corneal radius of curvature, and lens thickness were the most important determinants of refraction.

Metacognitions mediate HIV stigma and depression/anxiety in men who have sex with men living with HIV

The study examined whether the relationships between HIV stigma and depression and anxiety would be mediated by metacognitive beliefs and thought control strategies in men who have sex with men living with HIV. Men who have sex with men living with HIV completed an online survey that measured 30-item Metacognitions Questionnaire, thought control strategies (Thought Control Questionnaire), as well as symptoms of depression (Patient Health Questionnaire-9) and anxiety (generalized anxiety disorder-7). The relationships between internalised and anticipated HIV stigma with depressive symptoms were mediated by Negative Metacognitive Beliefs and the use of Worry and Social thought control strategies. Negative Metacognitive Beliefs mediated the association between internalised HIV stigma and anxiety symptoms.

"Why are you crying? You got what you wanted!": Psychosocial experiences of sex reassignment surgery

Little is known about the psychosocial needs of trans individuals as they make the surgical transition to their preferred gender. This qualitative study explored the lived experiences of 14 Australian trans men and women, aged between 25 and 78 who had undergone sex reassignment surgery to determine if their needs were met. The key findings suggest that while the surgery met their personal needs, there are inconsistencies in the level of care and support provided at the medical level throughout the transition process. In legal terms, the complex legislative framework does little but increase the psychosocial burden of Australian trans people.

Reduced incidence of foot-related hospitalisation and amputation amongst persons with diabetes in Queensland, Australia

Objective To determine trends in the incidence of foot-related hospitalisation and amputation amongst persons with diabetes in Queensland (Australia) between 2005 and 2010 that coincided with changes in state-wide ambulatory diabetic foot-related complication management. Methods All data from cases admitted for the principal reason of diabetes foot-related hospitalisation or amputation in Queensland from 2005–2010 were obtained from the Queensland Hospital Admitted Patient Data Collection dataset. Incidence rates for foot-related hospitalisation (admissions, bed days used) and amputation (total, minor, major) cases amongst persons with diabetes were calculated per 1,000 person-years with diabetes (diabetes population) and per 100,000 person-years (general population). Age-sex standardised incidence and age-sex adjusted Poisson regression models were also calculated for the general population. Results There were 4,443 amputations, 24,917 hospital admissions and 260,085 bed days used for diabetes foot-related complications in Queensland. Incidence per 1,000 person-years with diabetes decreased from 2005 to 2010: 43.0% for hospital admissions (36.6 to 20.9), 40.1% bed days (391 to 234), 40.0% total amputations (6.47 to 3.88), 45.0% major amputations (2.18 to 1.20), 37.5% minor amputations (4.29 to 2.68) (p < 0.01 respectively). Age-sex standardised incidence per 100,000 person-years in the general population also decreased from 2005 to 2010: 23.3% hospital admissions (105.1 to 80.6), 19.5% bed days (1,122 to 903), 19.3% total amputations (18.57 to 14.99), 26.4% major amputations (6.26 to 4.61), 15.7% minor amputations (12.32 to 10.38) (p < 0.01 respectively). The age-sex adjusted incidence rates per calendar year decreased in the general population (rate ratio (95% CI)); hospital admissions 0.949 (0.942–0.956), bed days 0.964 (0.962–0.966), total amputations 0.962 (0.946–0.979), major amputations 0.945 (0.917–0.974), minor amputations 0.970 (0.950–0.991) (p < 0.05 respectively). Conclusions There were significant reductions in the incidence of foot-related hospitalisation and amputation amongst persons with diabetes in the population of Queensland over a recent six-year period.

Does gender moderate the relationship between polydrug use and sexual risk-taking among Australian secondary school students under 16 years of age?

Introduction and Aims This study examines the association of alcohol and polydrug use with risky sexual behaviour in adolescents under 16 years of age and if this association differs by gender. Design and Methods The sample consisted of 5412 secondary school students under 16 years of age from Victoria, Australia. Participants completed an anonymous and confidential survey during class time. The key measures were having had sex before legal age of consent (16 years), unprotected sex before 16 (no condom) and latent-class derived alcohol and polydrug use variables based on alcohol, tobacco, cannabis, inhalants and other illegal drug use in the past month. Results There were 7.52% and 2.55% of adolescents who reported having sex and having unprotected sex before 16 years of age, respectively. After adjusting for antisocial behaviours, peers' drug use and family and school risk factors, girls were less likely to have unprotected sex (odds ratio = 0.31, P = 0.003). However, the interaction of being female and polydrug use (odds ratio = 4.52, P = 0.004) was significant, indicating that girls who engaged in polydrug use were at higher risk of having unprotected sex. For boys, the effect of polydrug use was non-significant (odds ratio = 1.44, P = 0.310). Discussion and Conclusions For girls, polydrug use was significantly associated with unprotected sex after adjusting for a range of risk factors, and this relationship was non-significant for boys. Future prevention programs for adolescent risky sexual behaviour and polydrug use might benefit from a tailored approach to gender differences.