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Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.
Bovine trichomoniasis is a notifiable, reproductive disease of cattle caused by the parasite Tritrichomonas foetus. Culturing with modified Diamond's medium (MDM) is required to increase the low number of organisms received from a preputial sample, but is limited in application to remote areas as it requires continuous cold chain storage. This study utilized lyophilization to sustain the viability of MDM during transport in lieu of a continuous cold chain. All lyophilized MDM was able to sustain T. foetus after storage for 42 days at 24 °C, and the results demonstrated that lyophilized MDM was equally as viable as refrigerated liquid MDM. Storage of lyophilized MDM at room temperature for 1 and 7 days did not impact T. foetus yield, both with and without exposure to light. A limitation of the lyophilized MDM was demonstrated with a significant decrease in T. foetus yield when the media was stored at 37 and 58 °C. The lyophilization of MDM provides a robust method of transporting and storing medium prior to reconstitution and inoculation, for use in T. foetus diagnosis and surveillance in remote areas.
Tardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant improvements in centrally read Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with PBO and was generally well tolerated.
To evaluate the long-term efficacy of DTB in an open-label safety study following double-blind treatment using site-rated efficacy measures: AIMS, the Clinical Global Impression of Change (CGIC) and the Patient Global Impression of Change (PGIC), which may be used in real-world clinical practice settings.
Patients with TD who completed the parent studies were eligible to enter this open-label, long-term extension (OLE) after completing the 1-week washout period and final evaluation in the blinded portion of the trial. This extension comprised a 6-week titration period followed by a long-term maintenance phase. Patients began DTB at 12mg/day, titrating up to a maximum total dose of 48mg/day based on dyskinesia control and tolerability. Efficacy endpoints included in this analysis are the change in site-rated AIMS score (items 1–7) from parent study baseline, and the proportion of patients who were “Much Improved” or “Very Much Improved” (treatment success) on the CGIC and PGIC from OLE baseline.
At the end of the parent studies (Week 12), patients treated with DTB had experienced greater mean (standard error) improvements in site-rated AIMS score (–5.0[0.40]) than patients given PBO (–3.2[0.47]). With long-term DTB treatment, both groups experienced improvements in site-rated AIMS scores (prior DTB, –7.9[0.62]; prior placebo, –6.6[0.64]) compared with parent study baseline. Similarly, at the end of the parent studies, a greater proportion of patients treated with DTB had treatment success on the CGIC (DTB, 51%; PBO, 32%) and the PGIC (DTB, 46%; PBO: 33%); whereas at Week 54 of the OLE study, treatment success on CGIC and PGIC were similar in both the CGIC (prior DTB: 66%; prior PBO: 68%) and PGIC (prior DTB: 62%; prior PBO: 62%) groups. DTB was generally well tolerated.
Patients treated with DTB showed improvements in abnormal movements, as measured by site-rated AIMS, CGIC, and PGIC scores, which may be used in real-world clinical practice settings. These results corroborate the previously reported efficacy of DTB as observed in the 12-week, double-blind ARM-TD and AIM-TD trials, in which central raters were used to evaluate AIMS scores.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Do patients with acute illness admitted to the hospital and treated with liberal oxygen therapy compared with those treated with conservative oxygen therapy have differences in mortality and morbidity?
Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391(10131):1693–705.
To analyse the existing literature to assess the potential benefits or harms of supplemental oxygen use in acutely ill patients.
Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term “antibiotic never events” to globally recognize and define the most inappropriate antibiotic use.
In the final paragraph of The Origin of Species, Charles Darwin leaves us with the vision of Nature as an ‘entangled bank’, where individuals struggle to survive and reproduce in a world of competitors, predators, and parasites. In this chapter, I explore the games animals play in these struggles. Some are behavioural games, resulting in an extraordinary mix of cooperation and conflict in animal families, where sexual partners and parents and their offspring sometimes help one another, but sometimes cheat. Some are games played over evolutionary time, where strategies escalate over the generations between competitors, and between enemies and their victims, leading to extremes, not only in weaponry and cruelty, but in ornamentation and beauty, too. I illustrate these themes especially with examples of mating games in birds and evolutionary arms races between cuckoos and their hosts, to show how the rules of the games can be unravelled by a combination of bird watching and field experiments.
Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date.
Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972–79) and 4764 (mean age 37.7, born 1964–71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women.
In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45–76%) and unique environmental (40%; 95% CI 24–56%), but not shared environmental contributions (0%; 95% CI 0–0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD.
Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.
Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23–0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power differential (between voice and voice hearer) was the mediator of the treatment effect.
The trial sample (n = 197) was used. A logistic regression model predicting 18-month compliance was used to identify predictors, and an exploratory principal component analysis (PCA) of baseline variables used as potential predictors (confounders) in their own right. Stata's paramed command used to obtain estimates of the direct, indirect and total effects of treatment.
Voice omnipotence was the best predictor although the PCA identified a highly predictive cognitive-affective dimension comprising: voices’ power, childhood trauma, depression and self-harm. In the mediation analysis, the indirect effect of treatment was fully explained by its effect on the hypothesised mediator: voice power differential.
Voice power and treatment allocation were the best predictors of harmful compliance up to 18 months; post-treatment, voice power differential measured at nine months was the mediator of the effect of treatment on compliance at 18 months.