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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.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
In this article I press four different objections on Forst’s theory of the ‘Right to Justification’. These are (i) that the principle of justification is not well-formulated; (ii) that ‘reasonableness and reciprocity’, as these notions are used by Rawls, are not apt to support a Kantian conception of morality; (iii) that the principle of justification, as Forst understands it, gives an inadequate account of what makes actions wrong; and (iv) that, in spite of his protestations to the contrary, Forst’s account veers towards a version of moral realism that is prima facie incompatible with Kantian constructivism. I then evaluate Forst’s theory in the light of a distinction made by Sharon Street between restricted and unrestricted constructivism. I show that Forst has reason to deny that it is either the one or the other, but he is not able to show that it is both or neither. I conclude that the arguments Forst advances in support of his constructivist theory of the right to justification entail that it is a metaphysical and comprehensive conception in the relevant, Rawlsian sense. Forst’s theory of the right to justification therefore fails to fulfil one of the main stated aims.
How neighbourhood characteristics affect the physical safety of people with mental illness is unclear.
To examine neighbourhood effects on physical victimisation towards people using mental health services.
We developed and evaluated a machine-learning-derived free-text-based natural language processing (NLP) algorithm to ascertain clinical text referring to physical victimisation. This was applied to records on all patients attending National Health Service mental health services in Southeast London. Sociodemographic and clinical data, and diagnostic information on use of acute hospital care (from Hospital Episode Statistics, linked to Clinical Record Interactive Search), were collected in this group, defined as ‘cases’ and concurrently sampled controls. Multilevel logistic regression models estimated associations (odds ratios, ORs) between neighbourhood-level fragmentation, crime, income deprivation, and population density and physical victimisation.
Based on a human-rated gold standard, the NLP algorithm had a positive predictive value of 0.92 and sensitivity of 0.98 for (clinically recorded) physical victimisation. A 1 s.d. increase in neighbourhood crime was accompanied by a 7% increase in odds of physical victimisation in women and an 13% increase in men (adjusted OR (aOR) for women: 1.07, 95% CI 1.01–1.14, aOR for men: 1.13, 95% CI 1.06–1.21, P for gender interaction, 0.218). Although small, adjusted associations for neighbourhood fragmentation appeared greater in magnitude for women (aOR = 1.05, 95% CI 1.01–1.11) than men, where this association was not statistically significant (aOR = 1.00, 95% CI 0.95–1.04, P for gender interaction, 0.096). Neighbourhood income deprivation was associated with victimisation in men and women with similar magnitudes of association.
Neighbourhood factors influencing safety, as well as individual characteristics including gender, may be relevant to understanding pathways to physical victimisation towards people with mental illness.
Cardiac surgical interventions for children with trisomy 18 and trisomy 13 remain controversial, despite growing evidence that definitive cardiac repair prolongs survival. Understanding quality of life for survivors and their families therefore becomes crucial. Study objective was to generate a descriptive summary of parental perspectives on quality of life, family impact, functional status, and hopes for children with trisomy 18 and trisomy 13 who have undergone heart surgery.
A concurrent mixed method approach utilising PedsQL™ 4.0 Generic Core Parent Report for Toddlers or the PedsQL™ Infant Scale, PedsQL™ 2.0 Family Impact Module, Functional Status Scale, quality of life visual analogue scale, and narrative responses for 10 children whose families travelled out of state to access cardiac surgery denied to them in their home state due to genetic diagnoses.
Parents rated their child’s quality of life as 80/100, and their own quality of life as 78/100 using validated scales. Functional status was rated 11 by parents and 11.6 by providers (correlation 0.89). On quality of life visual analogue scale, all parents rated their child’s quality of life as “high” with mean response 92.7/100. Parental hopes were informed by realistic perspective on prognosis while striving to ensure their children had access to reaching their full potential. Qualitative analysis revealed a profound sense of the child’s relationality and valued life meaning.
Understanding parental motivations and perceptions on the child’s quality of life has potential to inform care teams in considering cardiac interventions for children with trisomy 18 and trisomy 13.
Peter Hill, one of the leading British pianists and musicologists of his generation.,
Thalia Myers, association with the music of Howard Skempton dates from 1995, when she commissioned Cantilena for the first Spectrum (for the ABRSM, the Associated Board of the Royal Schools of Music).,
John Tilbury, Polish government scholarship where he studied with Zbigniew Drzewiecki and co-founded the Warsaw Music Workshop group with Zygmunt Krause.,
James Weeks, published by University of York Music Press.,
Howard Skempton, none
This chapter captures the voices of some leading performers of Howard Skempton's music: Peter Hill (PH), Thalia Myers (TM), John Tilbury (JT), James Weeks (JW), interviewed by Cavett (EC) and collated by Head. The chapter concludes with a few words from Skempton (HS). For details of Skempton pieces see the Authorized Worklist (Appendix One). For information about recordings, see the Discography (Appendix Two). Author-date references in the transcripts below are to items in the select bibliography, unless they are further annotated ‘Discography’.
“SIMPLICITY ABOUT HIM”: FIRST ENCOUNTERS WITH SKEMPTON
PH: I got to know Howard in the early 1970s through my sister who worked at Faber Music, as did Howard. The first time we met was at a supper party for my sister's colleagues and for composers associated with Faber. Howard at once impressed me as a person of complete artistic integrity, and when he talked about his music he had a sincerity that made a refreshing change from the relentlessly competitive and over-professionalized ambience of the Royal College of Music where I was then a student. He was engaged in writing miniatures, many of them for piano, each of which was a distillation of weeks or even months of thought. Indeed, Howard told me he liked the mundane office work he did at Faber since it left his mind free to concentrate on his music. I had the impression of someone who thought very deeply about very simple things, and he explained that for him composition involved paring his ideas down to their essentials. The appeal of his music to me was that it embodied the principle of “less is more,” in which every sound mattered, instead of being lost in a maze of complexity. Although his manner was serious, Howard was not solemn. I can still recall from that evening that he amused us all with a lengthy saga of the accumulated mishaps that had befallen him on a trip to the launderette – making us laugh through his ability to look at the everyday in a quirky way that brought out the unexpected in things we take for granted.
What Howard was writing at that time was so at odds with the world of contemporary music, as it then was, that one didn't think of him as a “career” composer.
Jaswal & Akhtar provide several quotes ostensibly from people with autism but obtained via the discredited techniques of Facilitated Communication and the Rapid Prompting Method, and they do not acknowledge the use of these techniques. As a result, their argument is substantially less convincing than they assert, and the article lacks transparency.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
This chapter covers past and present research on romantic love, with an emphasis on recent scholarship in this area. We begin with an overview of definitions and theories of romantic love, continue with a focus on the biological basis of love (including several recent fMRI studies), and finish with an emphasis on maintaining long-term romantic love. We consider research on romantic love from a variety of theoretical perspectives including cross-cultural models, attachment theoretical approaches, evolutionary models, and in light of the self-expansion model. In addition, we consider the dark side of love, which can result in a variety of emotional responses and can potentially lead to loss of self. We also suggest fruitful areas for future research, including the effects of falling in love on the self, the processes and motivations associated with unrequited love, and the course of passionate love over time including potential moderators of that course. All work in this area converges on the idea that romantic love is an essential human experience that is worthy of future study. Though much progress has been made, there is still much to be done.
A substantial subset of people with psychotic disorders are first diagnosed in old age, yet little is known about the epidemiology of very late-onset schizophrenia-like psychosis. We investigated the incidence of affective and non-affective psychotic disorders in those aged 65 and above, and examined variation related to potential risk factors via systematic literature review. We searched PubMed, PsychInfo, Web of Science and bibliographies and directly contacted authors to obtain citations published between 1960 and 2016 containing (derivable) incidence data. Cases were those diagnosed with non-organic psychotic disorders after age 65. Findings were presented narratively, and random-effects meta-analyses were used to obtain pooled incidence rates. From 5687 citations, 41 met inclusion criteria. The pooled incidence of: affective psychoses was 30.9 per 100 000 person-years at risk (100 kpy) [95% confidence interval (CI) 11.5–83.4; I2 = 0.99], and schizophrenia was 7.5 per 100 kpy (95% CI 6.2–9.1; I2 = 0.99), with some evidence of higher schizophrenia rates in women [odds ratio (OR) = 1.6; 95% CI 1.0–2.5, p = 0.05]. We found narrative evidence of increasing incidence rates of non-affective psychoses with age, and higher rates amongst migrants than baseline populations, but no evidence that incidence varied by study quality or case ascertainment period (quality OR = 1.04; 95% CI 0.74–1.48; time period OR = 1.00; 95% CI 0.95–1.05). Substantial heterogeneity in the incidence of very late-onset schizophrenia-like psychoses was observed. No identified studies examined possible risk factors which may account for such variation, including socio-economic status, sensory impairment, traumatic life events, or social isolation.
The effects of long-distance maritime trade on the economic and political development of the hinterlands of port-cities are as evident on either side of the Red Sea as in South-East Asia. Both great powers of the west profited from the India trade in the fifth century, but with the deterioration in their relations after the 502–5 war, the Persians imposed an embargo on Roman trade with India, which Justinian tried and failed to break. Hence it was mainly through Persia that the products of the south and the east, including garnets from south India and Sri Lanka, reached Europe. The gold received in tribute from the Romans was probably destined for India. Close attention should be paid to references to trade in contemporary writings by members of elites which were largely indifferent to economic matters. They reveal inter alia the existence of a powerful business lobby in the Sasanian Empire.
While the early Roman centuries marked the high point of Mediterranean economic activity before the early modern period, it was in late antiquity that the growth of commerce gathered way in the wider world. There was increased traffic across Eurasia, from the late fourth century, when the city-states of Sogdia took control of the overland routes between China and the west, as well as those running south across the mountains to the subcontinent. This development in the north was dwarfed by the growth of longdistance trade by sea and of a series of interconnected maritime markets, itself facilitated by the extension of the Indian cultural zone over South-East Asia, as nascent states on the mainland and islands adopted Indian modes of rule and Buddhist beliefs. To the west of the subcontinent, in the Indian Ocean, there was increasing activity. Manufactured goods and natural products were exchanged between the Roman Empire, south Arabia, East Africa, the Persian Gulf, India and Sri Lanka. Growth continued in late antiquity, boosted, in the fifth century, by the opening of a direct sea route, through the Straits of Malacca, between the southern and eastern oceans. This facilitated trade between the Indian Ocean world and south China, and opened up the Java Sea as an active zone of exchange.