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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.
Although the study of concept knowledge has long been of interest in psychology and philosophy, it is only in the past two decades that it has been possible to characterize the neural implementation of concept knowledge. With the use of neuroimaging technology, it has become possible to ask previously unanswerable questions about the representation of concepts, such as the semantic composition of a concept in its brain representation. In particular, it has become possible to uncover some of the fundamental dimensions of representation that characterize several important domains of concepts.
Post-traumatic amnesia (PTA) is a transient period of recovery following traumatic brain injury (TBI) characterised by disorientation, amnesia, and cognitive disturbance. Agitation is common during PTA and presents as a barrier to patient outcome. A relationship between cognitive impairment and agitation has been observed. This prospective study aimed to examine the different aspects of cognition associated with agitation.
The sample comprised 82 participants (75.61% male) admitted to an inpatient rehabilitation hospital in PTA. All patients had sustained moderate to extremely severe brain injury as assessed using the Westmead Post-Traumatic Amnesia Scale (WPTAS) (mean duration = 42.30 days, SD = 35.10). Participants were assessed daily using the Agitated Behaviour Scale and WPTAS as part of routine clinical practice during PTA. The Confusion Assessment Protocol was administered two to three times per week until passed criterion was achieved (mean number assessments = 3.13, SD = 3.76). Multilevel mixed modelling was used to investigate the association between aspects of cognition and agitation using performance on items of mental control, orientation, memory free recall, memory recognition, vigilance, and auditory comprehension.
Findings showed that improvement in orientation was significantly associated with lower agitation levels. A nonsignificant trend was observed between improved recognition memory and lower agitation.
Current findings suggest that the presence of disorientation in PTA may interfere with a patient’s ability to understand and engage with the environment, which in turn results in agitated behaviours. Interventions aimed at maximizing orientation may serve to minimize agitation during PTA.
A coupled accelerator mass spectrometer–gas interface system has been successfully operating at the Hertelendi Laboratory of Environmental Studies, Debrecen, Hungary, since 2013. Over the last 6 years more than 500 gas targets were measured below 100 µg carbon content for carbon isotopic composition. The system was tested with blanks, OxII, IAEA-C1, IAEA-C2, and IAEA-C7 standards. The performance of our instrumentation shows good agreement with other published gas-interface system data and also shows a quite good agreement with the nominal value of international standard samples. There is a measurable but quite small memory effect after modern samples, but this does not significantly affect the final results. Typical ion currents at the low energy side were between 10–15 µA with a 5% CO2 in He mixing ratio. The relative errors average ±6% for samples greater than or equal to 10 µgC sample with mean count rates of 300 counts per microgram C for OxII. The blank is comparable with other systems, which is 0.0050 ± 0.0018 F14C or 34,000–47,000 yr BP, which allows for the routine measurement of both of small environmental and archeological samples.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
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Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
In this study, we propose a hypothesis that domain-general auditory processing, a perceptual anchor of L1 acquisition, can serve as the foundation of successful post-pubertal L2 learning. This hypothesis was tested with 139 post-pubertal L2 immersion learners by linking individual differences in auditory discrimination across multiple acoustic dimensions to the segmental, prosodic, lexical, and morphosyntactic dimensions of L2 proficiency. Overall, auditory processing was a primary determinant of a range of participants’ proficiency scores, even after biographical factors (experience, age) were controlled for. The link between audition and proficiency was especially clear for L2 learners who had passed beyond the initial phase of immersion (length of residence > 1 year). The findings suggest that greater auditory processing skill benefits post-pubertal L2 learners immersed in naturalistic settings for a sufficient period of time by allowing them to better utilize received input, which results in greater language gains and leads to more advanced L2 proficiency in the long run (similar to L1 acquisition).
Nineteen Eighty-Four has become part of our collective mental furniture. Its phrases structure our journalism. Its ideas inform our critiques of the present and the politics it shapes. Its future has become our past, yet its account of that future determines how we talk about the present as it continually threatens to transform into something menacing, unpredictable, and strange. This chapter reflects on the implications of what this inseparability of imagined past, increasingly fictional present, and not-yet-assured future says about our attitude to the dystopian imaginary and the place of Orwell’s novel within it. The chapter also examines why we value Nineteen Eighty-Four, sometimes unthinkingly, offering a commentary on its popularity and prestige at times of creeping authoritarian politics. It discusses the relevance of Orwell’s novel to more recent debates about post-truth politics, surveillance, with gestures to theories of simulation, culturalization, and the hyperreal.
This manuscript describes the institutional and clinical considerations that apply to the question of whether to mandate opioid dose reduction in patients who have received opioids long-term. It describes how a calamitous rise in addiction and overdose involving opioids has both led to a clinical recalibration by healthcare providers, and to strong incentives favoring forcible opioid reduction by policy making agencies. Neither the 2016 Guideline issued by the Centers for Disease Control and Prevention nor clinical evidence can justify or promote such policies as safe or effective.
A wealth of research documents the rise of affective polarization, or the increasing disdain for the out-party in American politics. In this paper, we analyze ANES data from 1988 to 2016 to investigate the contribution of core value polarization to the phenomenon of out-party enmity. We find that greater differences in fundamental principles relate significantly to emotionally intense evaluations of the opposing party and its candidates, as well as the ideological out-group, independent of issue attitude extremity and the strength of one's partisan and ideological identities. Moreover, ANES panel data from 1992 to 1996 reveal that past value extremity promotes future affective polarization. These results are important for our understanding of the nature and extent of value-based polarization in American politics.
An important component of reintroduction is acclimatization to the release site. Movement parameters and breeding are common metrics used to infer the end of the acclimatization period, but the time taken to locate preferred food items is another important measure. We studied the diet of a reintroduced population of brushtail possums Trichosurus vulpecula in semi-arid South Australia over a 12 month period, investigating changes over time as well as the general diet. We used next-generation DNA sequencing to determine the contents of 253 scat samples, after creating a local plant reference library. Vegetation surveys were conducted monthly to account for availability. Dietary diversity and richness decreased significantly with time since release after availability was accounted for. We used Jacob's Index to assess selectivity; just 13.4% of available plant genera were significantly preferred overall, relative to availability. The mean proportion of preferred plant genera contained within individual samples increased significantly with time since release, but the frequency of occurrence of preferred plants did not. Five genera (Eucalyptus, Petalostylis, Maireana, Zygophyllum and Callitris) were present in more than half of samples. There was no difference in dietary preferences between sexes (Pianka overlap = 0.73). Our results suggest that acclimatization periods may be longer than those estimated via reproduction, changes in mass and movement parameters, but that under suitable conditions a changeable diet should not negatively affect reintroduction outcomes. Reintroduction projects should aim to extend post-release monitoring beyond the dietary acclimatization period and, for dry climates, diet should be monitored through a drought period.
It is traditionally taught that the location to place an ultrasound probe to detect a pneumothorax with point-of-care ultrasound (POCUS) is the anterior chest, given the theory that air will collect at the least dependent area in the supine patient. There is a wide variety of scanning protocols with varying accuracy and completeness. We sought to assess the optimal area to scan for diagnosing pneumothorax by mapping the location of traumatic pneumothorax on computed tomography (CT).
Patients were selected after a retrospective cohort of adult patients who presented to a regional trauma center with a pneumothorax diagnosed on CT. Data were extracted using a standardized data collection tool, and 20% of charts were reviewed by two reviewers. Predefined zones were used to map the areas of pneumothoraces. Theoretical sensitivity and 95% confidence intervals (CIs) are reported.
A total of 203 traumatic pneumothoraces were reviewed from 2006 to 2016. The majority of the pneumothoraces were found in an area defined by the para-sternal border and the mid-clavicular line from the inferior aspect of the clavicle to the physiologic lung point (liver on the right, heart on the left). The theoretical sensitivity for pneumothorax of scanning this area was 91.6% (95% CI, 86.9–95%).
This study suggests any POCUS scanning protocol for traumatic pneumothorax should include an area from the inferior border of the clavicle at the parasternal border down to the liver or cardiac lung points and then the mid clavicular line down to the liver or cardiac lung points.
Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3–4.5 h period.
The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke.
Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3–4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel–Haenszel method and random-effects model were also employed.
Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94).
Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk–benefit ratio in the use of IVtPA.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
New collections are reported of the monospecific genus Polypyrenula, an apparently extinct and doubtfully lichenized fungus, typically classified in the Pyrenulaceae. Anatomical studies reveal that it is facultatively lichenized. The structure of its hamathecium suggests affinities with Dothideomycetes rather than Eurotiomycetes. Molecular analysis using nuLSU and mtSSU markers demonstrates for the first time its inclusion in Trypetheliaceae, outside the core genera as part of the early diverging lineages in this family. The known distribution of Polypyrenula is extended to Mexico and South America, new information on its phorophyte associations is provided, and the name Polypyrenula sexlocularis is reinstated as the correct name for this species.
Refractory ventricular fibrillation encountered during cardiac arrest has a mortality rate of 97%.1 As per the advanced cardiac life support (ACLS) guidelines, the management algorithm of ventricular fibrillation consists of chest compressions, epinephrine, defibrillation, and anti-arrhythmics.2 There have been reports describing the use of the fast-acting selective β-blocker, esmolol, and dual-sequential defibrillation in the management of ventricular fibrillation that is refractory to standard ACLS. We present a case of a 24-year-old male who had an out-of-hospital cardiac arrest, with refractory ventricular fibrillation despite high-quality cardiopulmonary resuscitation (CPR) and ACLS management. Along with standard ACLS, triple-sequential defibrillation was used to achieve return of spontaneous circulation (ROSC) after 82 minutes of downtime. An electrocardiogram (ECG) after ROSC showed an ST-elevation myocardial infarction (MI), and the patient underwent angiography showing a 100% occlusion of his left anterior descending artery. Following management of his coronary artery disease, he was discharged from the hospital 16 days later and was neurologically intact.
Louis-Napoléon Geoffroy is usually credited as the author of the first ‘alternate history’. Karen Hellekson asserts confidently that ‘the alternate history did not exist in Western literature until 1836’, the ‘year that saw the first novel-length alternate history, Louis-Napoléon Geoffroy- Château's Napoléon et la conquête du monde 1812–32’ (Alternate History 13), and Paul K. Alkon describes Geoffroy's novel as ‘the first uchronia of alternate history’ (Origins of Futuristic Fiction 146). This belief connects with a larger thesis, to which many scholars of science fiction subscribe, that the late eighteenth-century flourish of political revolutions across Europe and America, into which we may bracket the effectively global Napoleonic wars to which they gave rise, reconfigured the logic of the genre; that, as Darko Suvin puts it, ‘around 1800, space loses its monopoly upon the location of estrangement and the alternative horizons shift from space to time’ (Positions and Suppositions in Science Fiction 89). Revolution, the argument runs, challenged the older preconceptions about history as such, undid perceived inevitabilities and opened the door to imagined alterities. Out of this rupture emerged, inter alia, alternate history as a new sub-genre, fully formed in Geoffroy's novel, as abruptly as Athena bursting from the forehead of Jove. It is an argument unlikely to be disturbed by the observation that, in fact, there were many earlierpublished novels with good claims to be alternate histories, going back to the middle of the seventeenth century.
So instead of trying to unseat Geoffroy from his position of absolute priority, this chapter will start with the observation that there is a reason why his name stands, conventionally, at the origin point of alternate history. Something about Geoffroy's particular approach proved influential in subsequent iterations of the mode, sometimes at secondhand; and this fact has had profound consequences for how history as such is portrayed in science fiction. And indeed we need not look far to see what this is: the ideological valence of his subject, the way Napoleon blasts through the obstacle of ‘actual’ history by sheer force of military, political, and persona charisma. Geoffroy was a man who hero-worshipped Napoleon (he changed his first name from Louis to Louis-Napoléon in homage, for instance), and the whole of his novel makes quite plain his investment in a ‘great man’ model of history.