A life without stigma

Stigma stops people asking for help and getting the treatment and support they need. It makes it more difficult to find somewhere decent to live, a job, a mortgage, or insurance. It can make it more difficult to get help to look after children, make friends, feel good about yourself, or even to feel that life is worth living. Stigma is a major barrier to recovery. If people with mental illness are to be included as equal members of our society, then stigma and its associated discrimination must be eliminated.This report examines the impact stigma has on the lives of people affected by mental illness, including an overview of associated issues from the growing body of research in this area. It describes some of the major stigma-reduction initiatives carried out in Australia and overseas, looks at the evidence base to identify what works, and makes recommendations for future action in Australia to create a life without stigma

Why Military Matters: Re Colonel Arid; Ex parte Alpert and the 'Service Connection' Test versus the 'Service Status' Test: Competing Approaches to the Triggering of the Defence Power

With political changes afoot in both Australia and the United States, it is timely to review military regimes and remind ourselves how greatly they matter. Section 51(vi) of the Constitution authorises the Commonwealth Parliament to legislate with respect to: ‘The naval and military defence ofthe Commonwealth and of the several States and the control of the forces to execute and maintain the laws of the Commonwealth…’ One of the concerns in relation to s 51(vi) has been whether this provision supports the establishment of military tribunals and, further, whether these tribunals canbe regarded as exercising judicial power of the Commonwealth and thus be regarded as properly constituted courts for the purposes of Ch III of the Australian Constitution. The High Court’s 2004 decision in Re Colonel Aird; Ex parte Alpert has established that military tribunals and, more generally, the military discipline system will be regarded as constitutionallyvalid and a properly constituted court for the purposes of Ch III provided that it is applied to conduct which can be regarded as ‘service connected’ or invoked for the purposes of enforcing and maintaining discipline among the defence forces. This article examines the decision in Aird’s Case and the associated ‘service connection’ test as a basis for supporting the constitutional validity of the military tribunal system. The concluding section of the article develops some further observations on the newly created Australian Military Court

Precise Installation of Diazo-Tagged Side-Chains on Proteins to Enable In Vitro and In-Cell Site-Specific Labeling.

The chemistry of diazo compounds has generated a huge breadth of applications in the field of organic synthesis. Their versatility combined with their tunable reactivity, stability, and chemoselectivity makes diazo compounds desirable reagents for chemical biologists. Here, we describe a method for the precise installation of diazo handles on proteins and antibodies in a mild and specific approach. Subsequent 1,3-cycloaddition reactions with strained alkynes enable both bioimaging through an in-cell "click" reaction and probing of the cysteine proteome in cell lysates. The selectivity and efficiency of these processes makes these suitable reagents for chemical biology studies

Risk attitudes and personality traits predict perceptions of benefits and risks for medicinal products: a field study of European medical assessors

Background: Risk attitudes and personality traits are known predictors of decision making among laypersons, but very little is known of their influence among experts participating in organizational decision making. Methods: Seventy-five European medical assessors were assessed in a field study using the Domain Specific Risk Taking scale and the Big Five Inventory scale. Assessors rated the risks and benefits for a mock “clinical dossier” specific to their area of expertise, and ordinal regression models were used to assess the odds of risk attitude or personality traits in predicting either the benefit or the risk ratings. Results: An increase in the “conscientiousness” score predicted an increase in the perception of the drug’s benefit, and male assessors gave higher scores for the drug’s benefit ratings than did female assessors. Extraverted assessors saw fewer risks, and assessors with a perceived neutral-averse or averse risk profile saw greater risks. Conclusions: Medical assessors perceive the benefits and risks of medicines via a complex interplay of the medical situation, their personality traits and even their gender. Further research in this area is needed to determine how these potential biases are managed within the regulatory setting

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Food restriction reduces neurogenesis in the avian hippocampal formation

The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis) in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the hypothesis that the response to stressors in the avian hippocampal formation is homologous to that of the mammalian hippocampus

Ethnic differences in the association between depression and chronic pain:cross sectional results from UK Biobank

&lt;b&gt;Background&lt;/b&gt; Comorbid chronic pain and depression is a challenging dyad of conditions to manage in primary care and reporting has shown to vary by ethnic group. Whether the relationship between depression and chronic pain varies by ethnicity is unclear. This study aims to explore chronic pain and depression reporting across ethnic groups and examine whether this association differs, independently of potential confounding factors. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Cross-sectional study of UK Biobank participants with complete data on chronic pain and probable lifetime history of depression, who reported their ethnic group as White, Asian/Asian British or Black/Black British. Chronic pain classification: present if participants had ≥ 1 site of body pain (up to seven sites or “pain all over the body” could be selected) that lasted ≥ 3 months; extent of chronic pain categories: 0, 1, 2–3, 4–7 sites or pain all over the body. Probable depression classification: an algorithm of low mood, anhedonia and help-seeking behaviour. Relationship between depression and presence/extent of chronic pain assessed using logistic/multinomial regression models (odds ratio (OR); relative risk ratio (RRR), 95 % confidence intervals), adjusted for sociodemographic, lifestyle, and morbidity factors; and a final adjustment for current depressive symptoms. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The number of participants eligible for inclusion was 144,139: 35,703 (94 %) White, 4539 (3 %) Asian, and 3897 (3 %) Black. Chronic pain was less (40.5 %, 45.8 %, 45.0 %, respectively) and depression more (22.1 %, 12.9 %, 13.8 %, respectively) commonly reported in White participants than Asian and Black participants. Statistically significant associations between depression and presence/extent of chronic pain persisted following adjustment for potential confounding variables; this relationship was strongest for Black participants (presence of chronic pain: OR 1.86 (1.52, 2.27); RRR 1 site 1.49 (1.16, 1.91), 2–3 sites 1.98 (1.53, 2.56), 4–7 sites 3.23 (2.09, 4.99), pain all over the body 3.31 (2.05, 5.33). When current depressive symptoms were considered these relationships were attenuated. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Chronic pain and depression reporting varies across ethnic groups. Differences in health seeking behaviour between ethnic groups may impact on the results reported. Clinicians, particularly in primary care, need to be aware of the cultural barriers within certain ethic groups to expressing concern over mood and to consider their approach accordingly