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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
In this retrospective cohort study of patients presenting to a national direct-to-consumer medical practice, we found that provider geographic location is a stronger driver of antibiotic prescribing than patient location. Physicians in the Northeast and South are significantly more likely than physicians in the West to prescribe antibiotics for upper respiratory infection and bronchitis.
Countries worldwide are experiencing a third wave of the coronavirus disease 2019 (COVID-19) pandemic. Government-imposed restrictive measures continue with undetermined effects on physical and mental health.
To compare child and adolescent mental health services (CAMHS) referrals over 11 months (January–November) in 2020, 2019 and 2018 and examine any impact the different phases of the COVID-19 restrictions might have on referral rates.
Monthly CAMHS Health Service Executive data were examined, covering a catchment population of 260 560 or 12.7% of all youth (age group 0–18 years) in Ireland. The total number of urgent and routine referrals, appointments offered, rates of non-attendances and discharge outcome are presented.
There was a significant drop in referrals in 2020, compared with prior years (χ2 = 10.3, d.f. = 2, P = 0.006). Referrals in 2020 dropped from March to May by 11% and from June to August by 10.3%. From September, both routine and urgent referrals increased by 50% compared with previous years (2018/2019), with the highest increase in November 2020 (180%). Clinic activity also increased from September, with double the number of out-patient appointments offered, compared with previous years (χ2 = 5171.72, d.f. = 3, P < 0.001) and lower (6.6%) rates of non-attendance (χ2 = 868.35, d.f. = 3, P < 0.001).
In 2020, following an initial decline, referrals to CAMHS increased consistently from September. Such unprecedented increase in referrals places further strain on services that are already underresourced and underfunded, with the likelihood of increased waiting lists post COVID-19. It is envisaged that once the pandemic is over, resources will be even more constrained, and CAMHS will be urgently in need of additional ring-fenced funding.
In this paper we propose that our understanding of pathocentric epistemic injustices can be enriched if they are theorised in terms of predicaments. These are the wider socially scaffolded structures of epistemic challenges, dangers, needs, and threats experienced by ill persons due to their particular emplacement within material, social, and epistemic structures. In previous work we have described certain aspects of these predicaments, such as pathocentric epistemic injustices and pathophobia. A wider systematic perspective is needed to integrate these and other concepts. By thinking predicamentally, we can better understand the interrelated social, epistemic, and practical obstacles experienced by ill persons and connect the many concepts available for theorising them (microaggessions, epistemic injustices, and so on).
The logarithmic helicospiral has been the most widely accepted model of regularly coiled molluscan form since it was proposed by Moseley and popularized by Thompson and Raup. It is based on an explicit assumption that shells are isometric and grow exponentially, and an implicit assumption that the external form of the shell follows the internal shape, which implies that the parameters of the spiral could be reconstructed from the external whorl profile. In this contribution, we show that these assumptions fail on all 25 gastropod species we examine. Using a dataset of 176 fossil and modern gastropod shells, we construct an empirical morphospace of coiling using the parameters of whorl expansion rate, translation rate, and rate of increasing distance from coiling axis, plus rate of aperture shape change, from their best-fit models. We present a case study of change in shell form through geologic time in the austral family Struthiolariidae to demonstrate the utility of our approach for evolutionary paleobiology. We fit various functions to the shell-coiling parameters to demonstrate that the best morphological model is not the same for each parameter. We present a set of R routines that will calculate helicospiral parameters from sagittal sections through coiled shells and allow workers to compare models and choose appropriate sets of parameters for their own datasets. Shell-form parameters in the Struthiolariidae highlight a hitherto neglected hypothesis of relationship between Antarctic Perissodonta and the enigmatic Australian genus Tylospira that fits the biogeographic and stratigraphic distribution of both genera.
Paul Feyerabend (1924–1994) acquired a variety of epithets during the latter stage of his career. The most persistent is perhaps Nature’s description of him as ‘the worst enemy of science’, later adopted as the title of an important collection of essays in his honour. The label encapsulates his bad reputation, at least within philosophy of science, which can be divided roughly into two aspects.
ABSTRACT IMPACT: ReacStick concussion testing and monitoring can serve as a 'vital sign for the brain', allowing for an immediate, objective assessment on the field or at the bedside. This project examines the entrepreneuship process from invention to commercialization. OBJECTIVES/GOALS: ReacStick is the first objective, portable, measure of concussion likelihood and severity and uses simple and complex reaction time testing. We detail the entrepreneurship process from product invention through its current mid-stage (patented, 20+ publications, etc.) to future commercialization for diverse applications. METHODS/STUDY POPULATION: ReacStick was invented in 2010 and underwent extensive testing and validation of the underlying innovations. The regulatory landscape of the product was examined, and 510(k) was found to be the best pathway. Competitive analysis was done examining alternative products and comparing against the current gold standards. A customer discovery process was undertaken, and stakeholders were interviewed for feedback and iteration. Testing and validation were completed with athletes, older adults, and people taking medications. An overview of the necessary commercialization concepts is: market opportunity/monetization, intellectual property considerations, regulatory processes, commercialization plan. RESULTS/ANTICIPATED RESULTS: ReacStick accurately predicts concussion and time to recovery and was patented through UM Tech Transfer in 2010, with 10 years currently remaining on the patent. Through customer discovery processes, athletics was determined to be the most viable first market to enter. Next steps include seeking additional patent protection, capital investors, delivery of minimum viable product followed by iteration and improvement for military, emergency medicine and acute care use. The current remaining timeline involves 12-18 months to commercialization and includes regulatory approval, additional patent protection, collaboration with regulatory consultants, capital fundraising and product production. DISCUSSION/SIGNIFICANCE OF FINDINGS: The research team has gone through a lengthy process toward commercialization of ReacStick. Proof of concept and extensive validation of the underlying technology have been completed and the regulatory process has been mapped. Our experience can serve as a model of many of the steps and challenges that lie on the path from lab to sale to end users.
The National Institute for Health and Care Excellence (NICE) informs us that the first-line treatments for behavioural and psychological symptoms of dementia (BPSD) are non-pharmacological. Although psychotropics used to be the main strategy in the management of behaviours that challenge, there has been an increase in the use of biopsychosocial formulations since 2010, and there are now over a dozen to choose from. However, many are overly focused on obtaining information about the agitation, and less specific about providing details of the actions required to manage the behaviours. The NICE guidelines too fail to provide specific guidance on which non-pharmacological approaches to use. This article argues for giving equal weight to both the collection of meaningful information and the development of ‘informed actions’, because it is the actions that lead to change. The article outlines a management programme providing a framework for the assessment, formulation and treatment of agitation in dementia. The work draws on theory, evidence-based practice and practice-based evidence to provide a model with sufficient structure and flexibility to be useful for clinicians across a range of settings and professional groups.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Firearm injuries are a significant public health problem. Prior studies have analyzed firearm death data or adult firearm injury data, but few studies have analyzed firearm injury data specifically among youth. To inform the current debate surrounding gun policy in the United States, this study aims to provide an estimate of the immense burden of youth firearm injury and its associated risk factors. Therefore, we performed a descriptive analysis of the Nationwide Emergency Department Sample (NEDS), the largest all-payer emergency department database in the United States, from January 2006 to September 2015. All patients age < 21 who presented with any diagnosis of firearm-related injuries were included.
There were an estimated 198,839 incidents of firearm-related emergency department visits for patients age < 21 from 2006 through 2015. After presenting to the ED, an estimated 11,909 cases resulted in death. The population adjusted rate of firearm-related emergency department visits was highest in the South and Midwest. This study demonstrates the significant burden of firearm injury among youth. Having a reliable estimate of the number of children harmed by firearms each year is a critical tool for policymakers — and may make common-sense gun safety measures more politically possible.
Data from multiple sources point to the desire for revenge in response to grievances or perceived injustices as a root cause of violence, including firearm violence. Neuroscience and behavioral studies are beginning to reveal that the desire for revenge in response to grievances activates the same neural reward-processing circuitry as that of substance addiction, suggesting that grievances trigger powerful cravings for revenge in anticipation of experiencing pleasure. Based on this evidence, the authors argue that a behavioral addiction framework may be appropriate for understanding and addressing violent behavior. Such an approach could yield significant benefits by leveraging scientific and public health-oriented drug abuse prevention and treatment strategies that target drug cravings to spur development of scientific and public-health-oriented “gun abuse” prevention and treatment strategies targeting the revenge cravings that lead to violence. An example of one such “motive control” strategy is discussed. Approaching revenge-seeking, violence, and gun abuse from the perspective of compulsion and addiction would have the added benefit of avoiding the stigmatization as violent of individuals with mental illness while also acknowledging the systemic, social, and cultural factors contributing to grievances that lead to violent acts.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
The purpose of this chapter is to explore the impact of the Global Financial Crisis (GFC) and austerity on collective bargaining and wage outcomes internationally. It takes as the starting point for its analysis the argument advanced in Chapter 1 that the current wave of austerity policies stems from a neoliberal economic consensus that has pervaded developed economies and emphasizes free markets, the removal of rigidities to capital and shrinking the state. That is a philosophy that in policy terms is the antithesis of one supportive of trade unions and collective bargaining, which are themselves under this ideology seen as impediments to markets and economic growth (Harvey, 2007). The chapter therefore adopts a perspective that sees the GFC and austerity as providing a convenient point from which to further consolidate neoliberalism's hold on society (McCann, 2013) and simultaneously undermine one of the chief forms of resistance – trade unions and collective bargaining.
The first part of the chapter focuses attention on exploring trends in collective bargaining in the EU and North America (US and Canada) in the post-GFC period. In doing so, it identifies a common trajectory in nation-state policies that encompasses a shift towards identifying the GFC as a public debt crisis; the blaming of trade unions and their members (in particular public sector workers) for the crisis; and the introduction of reforms to collective bargaining and union security designed to reinforce deflationary austerity policies. The chapter's second part then examines trends in wage growth and equality since 2008 and discusses the factors influencing them and the extent to which they can be viewed as a product of the neoliberal-informed economic policies and reforms adopted in response to the crisis.
Changes to collective bargaining in the EU
Institutional context of collective bargaining in the EU under austerity
Since 2000 there have been significant social, economic and political policy shifts that have fundamentally challenged the status of collective bargaining in the EU. Policies associated with a neoliberal agenda that view unions and collective bargaining as sources of rigidities in the market have been central to this change as the EU has focused on the neoliberal free market agenda of labour-market flexibility and downward pressure on terms and conditions to sustain economic growth (Waddington, Muller and Vandaele, 2019). This process of change received support from EU enlargement and the move towards economic and monetary union (EMU).
A 56-year-old woman with Down syndrome presented with right-sided weakness and dysarthria, and was found on CT/CTA to have a left middle cerebral artery infarct secondary to moyamoya disease. Her left posterior inferior cerebellar artery (PICA) was fed both by the left vertebral artery, and the left ascending pharyngeal artery (APA), with a variant origin from the internal carotid artery (ICA), then passing through the jugular foramen (Figure 1). Her right PICA originated exclusively from her right occipital artery, also via the jugular foramen (Figure 2). The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated from the brachiocephalic trunk. In addition, she had a trifurcated anterior cerebral artery (ACA), and just prior to this trifurcation, her left ACA was partially supplied by the left ICA, via a superior hypophyseal artery. This case is noteworthy for several reasons. First, though it is exceedingly rare to have the PICA supplied by the jugular branch of the APA, this is the first reported case with an ICA origin of that APA.1,2 The fact that both PICAs in this patient originate from the anterior circulation should remind clinicians that in unexplained posterior circulation infarctions, vascular anatomy should be explored, as carotid-vertebrobasilar anastomoses such as these are rare, but possible. Lastly, the conjunction of moyamoya disease and anomalies of the vertebrobasilar system in a patient with Down syndrome raises interesting questions about the influence of trisomy 21 on the developing vasculature. Connections from the APA to the vertebrobasilar system are hypothesized to result from a lack of regression of an embryological anastomosis, in line with the more common persistent trigeminal and persistent hypoglossal arteries.1 Patients with moyamoya disease have a significantly higher rate of persistent carotid-vertebrobasilar anastomoses than the general population,3 and are also 26 times more likely to have Down syndrome.4 Correspondingly, patients with Down syndrome have significantly higher levels of moyamoya disease, and are more than 10 times as likely as the general population to have abnormalities of the Circle of Willis5 and vertebral arteries.6 Several genes on chromosome 21 are known to affect angiogenesis, namely collagen XIII/endostatin (COL18A1), DYRK1A, and Down syndrome candidate region 1 (DSCR1), possibly through inhibition of VEGF activity.7 Whether additional copies of these genes are responsible for the anomalous vascular development seen in Down syndrome, in turn predisposing to the development of moyamoya disease, could benefit from further exploration.
The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder.
Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder.
Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05).
Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Wild sheep and many primitive domesticated breeds have two coats: coarse hairs covering shorter, finer fibres. Both are shed annually. Exploitation of wool for apparel in the Bronze Age encouraged breeding for denser fleeces and continuously growing white fibres. The Merino is regarded as the culmination of this process. Archaeological discoveries, ancient images and parchment records portray this as an evolutionary progression, spanning millennia. However, examination of the fleeces from feral, two-coated and woolled sheep has revealed a ready facility of the follicle population to change from shedding to continuous growth and to revert from domesticated to primitive states. Modifications to coat structure, colour and composition have occurred in timeframes and to sheep population sizes that exclude the likelihood of variations arising from mutations and natural selection. The features are characteristic of the domestication phenotype: an assemblage of developmental, physiological, skeletal and hormonal modifications common to a wide variety of species under human control. The phenotypic similarities appeared to result from an accumulation of cryptic genetic changes early during vertebrate evolution. Because they did not affect fitness in the wild, the mutations were protected from adverse selection, becoming apparent only after exposure to a domestic environment. The neural crest, a transient embryonic cell population unique to vertebrates, has been implicated in the manifestations of the domesticated phenotype. This hypothesis is discussed with reference to the development of the wool follicle population and the particular roles of Notch pathway genes, culminating in the specific cell interactions that typify follicle initiation.
A novel inpatient vocational counseling service (named “In-Voc”) was developed and evaluated in three Australian spinal cord injury (SCI) rehabilitation hospitals, aiming to improve vocational outcomes after SCI. The program provided a trained Vocational Counseling Coordinator who worked alongside the allied health team, medical, and nursing staff at each hospital. The Coordinators were interviewed to examine the role expectations and role behaviors associated with the introduction of their novel, vocationally focused, occupational role. The Coordinators’ descriptions of their role behavior were very similar to those defined by rehabilitation counselors in North America. They reported the novel role to be a productive and satisfying one. Encouragingly, the In-Voc program was associated with significantly higher post-injury employment outcomes.