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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.
Longitudinal evaluation of allograft diastolic function in paediatric heart transplant recipients is important for early detection of acute rejection, cardiac allograft vasculopathy, and graft dysfunction. Mean diastolic right atrial and pulmonary capillary wedge pressures obtained at catheterisation are the reference standards for assessment. Echocardiography is non-invasive and more suitable for serial surveillance, but individual parameters have lacked accuracy. This study aimed to identify covariates of post-transplant mean right atrial and pulmonary capillary wedge pressures, including B-type natriuretic peptide and certain echocardiographic parameters.
A retrospective review of 143 scheduled cardiac catheterisations and echocardiograms from 56 paediatric recipients transplanted from 2007 to 2011 was performed. Samples with rejection were excluded. Univariate and multivariate linear regression models using backward selection were applied to a database consisting of B-type natriuretic peptide, haemodynamic, and echocardiographic data.
Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, mitral E/e’, and percent interventricular septal thickening in systole were independently associated with mean right atrial pressure. Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, left ventricular mass (observed/predicted), and mitral E/e’ were independently associated with mean pulmonary capillary wedge pressure. Covariates of B-type natriuretic peptide included mean pulmonary artery and pulmonary capillary wedge pressures, height, haemoglobin, fractional shortening, percent interventricular septal thickening in systole, and pulmonary vascular resistance index.
B-type natriuretic peptide and echocardiographic indices of diastolic function were independently related to post-transplant mean right atrial and pulmonary capillary wedge pressures in paediatric heart transplant recipients without rejection.
Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.
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.
Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.
Design, setting, participants, and measurements:
We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.
Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.
These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
In its 1930 Convention on Forced Labour, the International Labour Organization defined ‘forced or compulsory labour’ as ‘all work or service which is exacted from any person under the menace of any penalty and for which the said person has not offered himself voluntarily’. Representatives at the Geneva Convention further clarified forced labour as a particular ‘practice of compulsory labour exacted by a state or by agencies of a state, other than as a punishment for a criminal offence or for the purpose of the military defence’. Colonial powers faced enormous pressure to sign up to the 1930 ILO Convention, and several states delayed ratifying it. Despite this general agreement on the abolition of forced labour, despite increased pressure from non-governmental humanitarian groups and despite efforts by colonial reformers – including Jules Marcel de Coppet, the Governor General of French West Africa (1936–38), and Henrique Galvão, inspector of the Portuguese colonies and former governor of Huila Province in southern Angola – forced labour in colonial Africa persisted in many regions through the period of decolonization and into the present. Forced labour in twentieth-century Africa was a widespread means of building and maintaining infrastructure, supporting the mining sector and developing and servicing the export-oriented agricultural sector in French, German, Belgian, Portuguese, Italian and Spanish colonies, and, to a lesser degree, in the British colonies, where public labour ordinances, compulsory labour ordinances and communal labour ordinances served similar goals. Decolonization did not, however, end forced labour. Several postcolonial states have continued this practice, often under thinly disguised forms of military recruitment.
This chapter examines the variety of practices of forced labour during the colonial period on the African continent and its persistence into the postcolonial period. It provides a framework for understanding the context in which Western colonial powers engaged in forced labour and describes the major forms of forced labour used by both the colonial powers and the newly independent African nations. Forced labour was part of a wider set of practices using coerced labour. This chapter focuses on forced labour as a practice of state mobilization of labour in Africa during the twentieth century. As Frederick Cooper reminds us, during ‘the five hundred years in which Europeans and Africans have known each other rather well, no element has been more central in their relationship than work’. Forced labour was a central part of that relationship.
The traditional living donor was very healthy. However, as the supply-demand gap continues to expand, transplant programs have become more accepting of less healthy donors. This paper focuses on the other extreme, asking whether and when individuals who have life-limiting conditions (LLC) should be considered for living organ donation. We discuss ethical issues raised by 1) donation by individuals with progressive severe debilitating disease for whom there is no ameliorative therapy; and 2) donation by individuals who are imminently dying or would die by the donation process itself.
The United States relies on uncompensated family caregivers to provide most of the long-term care required by older adults as they age. But such care comes at a significant financial cost to these caregivers in the form of lower lifetime earnings and diminished (or even no) Social Security retirement benefits, ineligibility for Medicare coverage of their healthcare costs, and minimal retirement savings. To reduce the impact of uncompensated caregiving on the intergenerational transmission of poverty, this paper discusses three possible mechanisms of compensating family caregivers: public payments, deemed wage credits under Social Security, and income tax incentives.
OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.
The ‘Landscapes of Production and Punishment’ project aims to examine how convict labour from 1830–1877 affected the built and natural landscapes of the Tasman Peninsula, as well as the lives of the convicts themselves.
Earlier reports have summarized crop yield losses throughout various North American regions if weeds were left uncontrolled. Offered here is a report from the current WSSA Weed Loss Committee on potential yield losses due to weeds based on data collected from various regions of the United States and Canada. Dry bean yield loss estimates were made by comparing dry bean yield in the weedy control with plots that had >95% weed control from research studies conducted in dry bean growing regions of the United States and Canada over a 10-year period (2007 to 2016). Results from these field studies showed that dry bean growers in Idaho, Michigan, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Ontario, and Manitoba would potentially lose an average of 50%, 31%, 36%, 59%, 94%, 31%, 71%, 56%, and 71% of their dry bean yield, respectively. This equates to a monetary loss of US $36, 40, 6, 56, 421, 2, 18, 44, and 44 million, respectively, if the best agronomic practices are used without any weed management tactics. Based on 2016 census data, at an average yield loss of 71.4% for North America due to uncontrolled weeds, dry bean production in the United States and Canada would be reduced by 941,000,000 and 184,000,000 kg, valued at approximately US $622 and US $100 million, respectively. This study documents the dramatic yield and monetary losses in dry beans due to weed interference and the importance of continued funding for weed management research to minimize dry bean yield losses.
The Yellow Chat Epthianura crocea is comprised of three disjunct subspecies. Subspecies E. c. macgregori (Capricorn Yellow Chat) is listed as Critically Endangered under the EPBC Act and has a distribution that also appears to be disjunct, with a limited geographic area of less than 7,000 ha. Some populations are threatened by rapid industrial development, and it is important for conservation of the subspecies to determine the extent to which the putative populations are connected. We used 14 microsatellite markers to measure genetic diversity and to determine the extent of gene flow between two disjunct populations at the northern and southern extremes of the subspecies’ range. No significant differences in genetic diversity (number of alleles and heterozygosity) were observed, but clear population structuring was apparent, with obvious differentiation between the northern and southern populations. The most likely explanation for reduced gene flow between the two populations is either the development of a geographic barrier as a consequence of shrinkage of the marine plains associated with the rise in sea levels following the last glacial maxima, or reduced connectivity across the largely unsuitable pasture and forest habitat that now separates the two populations, exacerbated by declining population size and fewer potential emigrants. Regardless of the mechanism, restricted gene flow between these two populations has important consequences for their ongoing conservation. The relative isolation of the smaller southern groups (the Fitzroy River delta and Curtis Island) from the much larger northern group (both sides of the Broad Sound) makes the southern population more vulnerable to local extinction. Conservation efforts should focus on nature refuge agreements with land owners agreeing to maintain favourable grazing management practices in perpetuity, particularly in the northern area where most chats occur. Supplemental exchanges of individuals from northern and southern populations should be explored as a way of increasing genetic diversity and reducing inbreeding.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
To determine the impact of an environmental disinfection intervention on the incidence of healthcare-associated Clostridium difficile infection (CDI).
A multicenter randomized trial.
In total,16 acute-care hospitals in northeastern Ohio participated in the study.
We conducted a 12-month randomized trial to compare standard cleaning to enhanced cleaning that included monitoring of environmental services (EVS) personnel performance with feedback to EVS and infection control staff. We assessed the thoroughness of cleaning based on fluorescent marker removal from high-touch surfaces and the effectiveness of disinfection based on environmental cultures for C. difficile. A linear mixed model was used to compare CDI rates in the intervention and postintervention periods for control and intervention hospitals. The primary outcome was the incidence of healthcare-associated CDI.
Overall, 7 intervention hospitals and 8 control hospitals completed the study. The intervention resulted in significantly increased fluorescent marker removal in CDI and non-CDI rooms and decreased recovery of C. difficile from high-touch surfaces in CDI rooms. However, no reduction was observed in the incidence of healthcare-associated CDI in the intervention hospitals during the intervention and postintervention periods. Moreover, there was no correlation between the percentage of positive cultures after cleaning of CDI or non-CDI rooms and the incidence of healthcare-associated CDI.
An environmental disinfection intervention improved the thoroughness and effectiveness of cleaning but did not reduce the incidence of healthcare-associated CDI. Thus, interventions that focus only on improving cleaning may not be sufficient to control healthcare-associated CDI.