Modelling the Genetic Risk in Age-Related Macular Degeneration

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS −0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available

Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation.

Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution

Probability of Major Depression Classification Based on the SCID, CIDI and MINI Diagnostic Interviews : A Synthesis of Three Individual Participant Data Meta-Analyses

Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics

Caring for the carers: Ensuring the provision of quality maternity care during a global pandemic.

The COVID-19 pandemic is impacting health systems worldwide. Maternity care providers must continue their core business in caring and supporting women, newborns and their families whilst also adapting to a rapidly changing health system environment. This article provides an overview of important considerations for supporting the emotional, mental and physical health needs of maternity care providers in the context of the unprecedented crisis that COVID-19 presents. Cooperation, planning ahead and adequate availability of PPE is critical. Thinking about the needs of maternity providers to prevent stress and burnout is essential. Emotional and psychological support needs to be available throughout the response. Prioritising food, rest and exercise are important. Healthcare workers are every country's most valuable resource and maternity providers need to be supported to provide the best quality care they can to women and newborns in exceptionally trying circumstances

Mental health of people in Australia in the first month of COVID-19 restrictions: a national survey

OBJECTIVES: To estimate the population prevalence of clinically significant symptoms of depression, generalised anxiety, thoughts of being better off dead, irritability, and high optimism about the future, and of direct experience of COVID-19, loss of employment caused by COVID-19 restrictions, worry about contracting COVID-19, or major disadvantage because of the restrictions; to examine the relationship between these experiences and reporting mental symptoms. DESIGN, SETTING, PARTICIPANTS: Anonymous online survey of adult Australian residents, 3 April - 2 May 2020. MAIN OUTCOME MEASURES: Self-reported psychological status during the preceding fortnight assessed with the Patient Health Questionnaire 9 (PHQ-9; symptoms of depression) and the Generalised Anxiety Disorder Scale (GAD-7). Optimism about the future was assessed with a 10-point study-specific visual analogue scale. RESULTS: 13 829 respondents contributed complete response data. The estimated prevalence of clinically significant symptoms of depression (PHQ-9 ≥ 10) was 27.6% (95% CI, 26.1-29.1%) and of clinically significant symptoms of anxiety (GAD-7 ≥ 10) 21.0% (95% CI, 19.6-22.4%); 14.6% of respondents (95% CI, 13.5-16.0%) reported thoughts of being better off dead or self-harm (PHQ-9, item 9) on at least some days and 59.2% (95% CI, 57.6-60.7%) that they were more irritable (GAD-7, item 6). An estimated 28.3% of respondents (95% CI, 27.1-29.6%) reported great optimism about the future (score ≥ 8). People who had lost jobs, were worried about contracting COVID-19, or for whom the restrictions had a highly adverse impact on daily life were more likely to report symptoms of depression or anxiety, and less likely to report high optimism than people without these experiences. CONCLUSIONS: Mental health problems were widespread among Australians during the first month of the stage two COVID-19 restrictions; in addition, about one-quarter of respondents reported mild to moderate symptoms of depression or anxiety. A public mental health response that includes universal, selective and indicated clinical interventions is needed