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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.
The majority of slave narratives published between 1840 and 1865 were produced by persons who came from what might be termed the elite slave minority, that is, from skilled workers, domestic workers, and headmen. Men and women from the relatively higher echelons of slavery contributed double the number of texts to the mid-century slave narrative than were produced by former field laborers, those who spent most of their working life in slavery doing the most grueling and punishing agricultural labor. In this chapter, class refers mainly to two kinds of differences observable in antebellum slave narratives: differences based on access to and/or control of material resources, such as money, property, and compensation for labor; and differences based on access to or control of social power and prestige based on factors such as occupation, wage earning, family status, and literacy.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number of referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult.
We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. Sites were selected from a convenience sample of older peoples liaison psychiatry departments. Departments from all regions of the UK were invited to participate via the RCPsych liaison and older peoples faculty email distribution lists. From departments who returned data, we combined the date and described trends in the number and rate of referrals over a 7 year period.
Referral data from up to 28 EDs across England and Scotland over a 7 year period were analysed (n = 18828 referrals). There is a general trend towards increasing numbers of older people referred to liaison psychiatry year on year. Rates rose year on year from 1.4 referrals per 1000 ED attenders (>65 years) in 2011 to 4.5 in 2019 . There is inter and intra site variability in referral numbers per 1000 ED attendances between different departments, ranging from 0.1 - 24.3.
To plan an effective healthcare system we need to understand the population it serves, and have appropriate structures and processes within it. The overarching message of this study is clear; older peoples mental health emergencies presenting in ED are common and appear to be increasingly so. Without appropriate investment either in EDs or community mental health services, this is unlikely to improve.
The data also suggest very variable inter-departmental referral rates. It is not possible to establish why rates from one department to another are so different, or whether outcomes for the population they serve are better or worse. The data does however highlight the importance of asking further questions about why the departments are different, and what impact that has on the patients they serve.
Ethnohistoric accounts indicate that the people of Australia's Channel Country engaged in activities rarely recorded elsewhere on the continent, including food storage, aquaculture and possible cultivation, yet there has been little archaeological fieldwork to verify these accounts. Here, the authors report on a collaborative research project initiated by the Mithaka people addressing this lack of archaeological investigation. The results show that Mithaka Country has a substantial and diverse archaeological record, including numerous large stone quarries, multiple ritual structures and substantial dwellings. Our archaeological research revealed unknown aspects, such as the scale of Mithaka quarrying, which could stimulate re-evaluation of Aboriginal socio-economic systems in parts of ancient Australia.
Antislavery writers experimented with the idea that slaves and masters might address each other through direct and formalized literary dialogues. To do so, these activists used pamphlets, a genre that had already enabled differing religious, political, and intellectual points of view to engage each other in eighteenth-century North America. In the deliberately double meaning of “salvation,” both political and religious, for both this world and the next, David Walker’s Appeal brings to bold fruition an idea only incipient in the dialogic experiments of Benjamin Banneker and Daniel Coker, that recognizing and following Black, not white, moral and spiritual leadership was the only hope for a slavery-corrupted America.
Glacier surges are periodic episodes of mass redistribution characterized by dramatic increases in ice flow velocity and, sometimes, terminus advance. We use optical satellite imagery to document five previously unexamined surge events of Sít’ Kusá (Turner Glacier) in the St. Elias Mountains of Alaska from 1983 to 2013. Surge events had an average recurrence interval of ~5 years, making it the shortest known regular recurrence interval in the world. Surge events appear to initiate in the winter, with speeds reaching up to ~25 m d−1. The surges propagate down-glacier over ~2 years, resulting in maximum thinning of ~100 m in the reservoir zone and comparable thickening at the terminus. Collectively, the rapid recurrence interval, winter initiation and down-glacier propagation suggest Sít’ Kusá's surges are driven by periodic changes in subglacial hydrology and glacier sliding. Elevation change observations from the northern tributary show a kinematic disconnect above and below an icefall located 23 km from the terminus. We suggest the kinematic disconnect inhibits drawdown from the accumulation zone above the icefall, which leads to a steady flux of ice into the reservoir zone, and contributes to the glacier's exceptionally short recurrence interval.
Coronavirus disease (COVID-19) has been identified as an acute respiratory illness leading to severe acute respiratory distress syndrome. As the disease spread, demands on health care systems increased, specifically the need to expand hospital capacity. Alternative care hospitals (ACHs) have been used to mitigate these issues; however, establishing an ACH has many challenges. The goal of this session was to perform systems testing, using a simulation-based evaluation to identify areas in need of improvement.
Four simulation cases were designed to depict common and high acuity situations encountered in the ACH, using a high technology simulator and standardized patient. A multidisciplinary observer group was given debriefing forms listing the objectives, critical actions, and specific areas to focus their attention. These forms were compiled for data collection.
Logistical, operational, and patient safety issues were identified during the simulation and compiled into a simulation event report. Proposed solutions and protocol changes were made in response to the identified issues.
Simulation was successfully used for systems testing, supporting efforts to maximize patient care and provider safety in a rapidly developed ACH. The simulation event report identified operational deficiencies and safety concerns directly resulting in equipment modifications and protocol changes.
HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities.
A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March–May 2016 and followed up March–May 2017.
HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records.
In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9–53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0–28.6 n = 16) was observed.
HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.
On October 10, 2020, the Memorial Sloan Kettering Cancer Center Supportive Care Service hosted their first-ever United States (US) World Hospice and Palliative Care Day (WHPCD) Celebration. The purpose of this article is to describe the US inaugural event in alignment with the broader goals of WHPCD and provide lessons learned in anticipation of the second annual conference to be held on October 5–6, 2021.
Description of the inaugural event in the context of COVID-19 and WHPCD, co-planning conference team reflection, and attendee survey responses.
The Worldwide Hospice Palliative Care Alliance initially launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care around the world. The US-based innovative virtual conference featured 23 interprofessional hospice and palliative care specialists and patient and family caregiver speakers across nine diverse sessions addressing priorities at the intersection of COVID-19, social injustice, and the global burden of serious health-related suffering. Two primary aims guided the event: community building and wisdom sharing. Nearly 270 registrants from at least 16 countries and one dozen states across the US joined the free program focused on both personal and professional development.
Significance of results
Unlike many other academic conferences and professional gatherings that were relegated to online forums due to pandemic-related restrictions, the US WHPCD Celebration was intentionally established to create a virtual coming together for collective reflection on the barriers and facilitators of palliative care delivery amid vast societal change. The goal to ensure a globally relevant and culturally inclusive agenda will continue to draw increased participation at an international level during future annual events. Finally, the transparent and respectful sharing of palliative care team experiences in the year preceding the conference established a safe environment for both individual expression and scholarly discussion.
In this study we report a new record of a cryptogenic polychaete from southern Africa. The species was found inhabiting sand tubes in intertidal sand flats in the Knysna Estuary on the southern coast of South Africa. Morphological comparisons using light and scanning electron microscopy showed extensive taxonomic similarities with Dipolydora socialis described from other localities and from museum vouchers. In addition, 18S rRNA and COI barcodes were generated for the species. Genetic analysis of the assembled polydorid dataset corroborated the morphological data in delineating the species as a taxonomic unit with >99% genetic similarity to available sequences of D. socialis in the GenBank database. Dipolydora socialis has been reported as having a widespread distribution, and since it can reside within tubes associated with fouling communities or as a shell borer, several vectors may have been responsible for its global spread and introduction to southern Africa. Finally, considering the many cryptic complexes that are currently being uncovered within polychaetes, including spionids, future taxonomic studies should incorporate additional genetic data from other regions of the world to determine whether D. socialis may also be part of a larger species complex.
Unexplained infertility refers to the inability to conceive within 12 months of unprotected intercourse, not attributable to any known causes of infertility such as ovulatory dysfunction, reduced sperm quality, tubal pathology or other causes. Treatment for unexplained infertility can be done predominantly through intrauterine insemination with or without hyperstimulation or in vitro fertilisation. Given that these treatments are utilised to improve likelihood of conception in relation to the couple’s chances of spontaneous pregnancy, rather than targeting any specific pathology, a comparison should be drawn between these treatments and their natural conception prognosis. Utilisation of prognostic models can allow differentiation between those likely to benefit from immediate treatment from such individuals who have reasonable natural conception prognosis and thereby can delay treatment for 6 months in hopes of spontaneous pregnancy. This comparison is valuable given the aforementioned treatments have implications for both the woman and her future child, and the cost of such procedures also compromises care accessibility.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Neo-Kantian philosophers see accountability as a key property of autonomy, or of social freedom more broadly. Autonomy, among those theorists, is, I contend, implicitly co-conceived with responsibility, producing a quasi-juridical conception of autonomy and a limiting notion of freedom. This article criticizes the connecting of freedom with accountability on a number of grounds. First, various conceptions of autonomy not only operate without a notion of accountability, but, in fact, would be impaired by an accountability requirement. Second, the neo-Kantians are unable to defend the freedom enhancing properties that are supposedly brought about by the giving of reasons for one’s beliefs and actions. Third, the project of accountability is indifferent to personal outlooks, not because it takes a holistic perspective, but because of its interest in social convergence.
Must we ascribe hope for better times to those who (take themselves to) act morally? Kant and later theorists in the Frankfurt School tradition thought we must. In this article, I disclose that it is possible – and ethical – to refrain from ascribing hope in all such cases. I draw on two key examples of acting irrespective of hope: one from a recent political context and one from the life of Jean Améry. I also suggest that, once we see that it is possible to make sense of (what I call) ‘merely expressive acts’, we can also see that the early Frankfurt School was not guilty of a performative contradiction in seeking to enlighten Enlightenment about its (self-)destructive tendencies, while rejecting the (providential) idea of progress.
Jürgen Habermas’ discourse theory of morality should be understood, in metaethical terms, as a constructivist theory. All constructivist theories face a Euthyphro-like dilemma arising from how they classify the constraints on their metaethical construction procedures: are they moral or non-moral? Many varieties of Kantian constructivism, such as Christine Korsgaard’s, classify the constraints as moral, albeit constitutive of human reason and agency in general. However, this constitutivist strategy is vulnerable to David Enoch’s ‘shmagency’ objection. The discourse theory of morality, by classifying the constraints on the metaethical construction procedure (principles (D) and (U)) as non-moral, can avoid this problem.