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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Planning mental health carer services requires information about the number of carers, their characteristics, service use and unmet support needs. Available Australian estimates vary widely due to different definitions of mental illness and the types of carers included. This study aimed to provide a detailed profile of Australian mental health carers using a nationally representative household survey.
The number of mental health carers, characteristics of carers and their care recipients, caring hours and tasks provided, service use and unmet service needs were derived from the national 2012 Survey of Disability, Ageing and Carers. Co-resident carers of adults with a mental illness were compared with those caring for people with physical health and other cognitive/behavioural conditions (e.g., autism, intellectual disability, dementia) on measures of service use, service needs and aspects of their caring role.
In 2012, there were 225 421 co-resident carers of adults with mental illness in Australia, representing 1.0% of the population, and an estimated further 103 813 mental health carers not living with their care recipient. The majority of co-resident carers supported one person with mental illness, usually their partner or adult child. Mental health carers were more likely than physical health carers to provide emotional support (68.1% v. 19.7% of carers) and less likely to assist with practical tasks (64.1% v. 86.6%) and activities of daily living (31.9% v. 48.9%). Of co-resident mental health carers, 22.5% or 50 828 people were confirmed primary carers – the person providing the most support to their care recipient. Many primary mental health carers (37.8%) provided more than 40 h of care per week. Only 23.8% of primary mental health carers received government income support for carers and only 34.4% received formal service assistance in their caring role, while 49.0% wanted more support. Significantly more primary mental health than primary physical health carers were dissatisfied with received services (20.0% v. 3.2%), and 35.0% did not know what services were available to them.
Results reveal a sizable number of mental health carers with unmet needs in the Australian community, particularly with respect to financial assistance and respite care, and that these carers are poorly informed about available supports. The prominence of emotional support and their greater dissatisfaction with services indicate a need to better tailor carer services. If implemented carefully, recent Australian reforms including the Carer Gateway and National Disability Insurance Scheme hold promise for improving mental health carer supports.
To determine which healthcare worker (HCW) roles and patient care activities are associated with acquisition of vancomycin-resistant Enterococcus (VRE) on HCW gloves or gowns after patient care, as a surrogate for transmission to other patients.
Prospective cohort study.
Medical and surgical intensive care units at a tertiary-care academic institution.
VRE-colonized patients on Contact Precautions and their HCWs.
Overall, 94 VRE-colonized patients and 469 HCW–patient interactions were observed. Research staff recorded patient care activities and cultured HCW gloves and gowns for VRE before doffing and exiting patient room.
VRE were isolated from 71 of 469 HCWs’ gloves or gowns (15%) following patient care. Occupational/physical therapists, patient care technicians, nurses, and physicians were more likely than environmental services workers and other HCWs to have contaminated gloves or gowns. Compared to touching the environment alone, the odds ratio (OR) for VRE contamination associated with touching both the patient (or objects in the immediate vicinity of the patient) and environment was 2.78 (95% confidence interval [CI], 0.99–0.77) and the OR associated with touching only the patient (or objects in the immediate vicinity) was 3.65 (95% CI, 1.17–11.41). Independent risk factors for transmission of VRE to HCWs were touching the patient’s skin (OR, 2.18; 95% CI, 1.15–4.13) and transferring the patient into or out of bed (OR, 2.66; 95% CI, 1.15–6.43).
Patient contact is a major risk factor for HCW contamination and subsequent transmission. Interventions should prioritize contact precautions and hand hygiene for HCWs whose activities involve touching the patient.
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.
Studies have consistently shown that subthreshold depression is associated with an increased risk of developing major depression. However, no study has yet calculated a pooled estimate that quantifies the magnitude of this risk across multiple studies.
We conducted a systematic review to identify longitudinal cohort studies containing data on the association between subthreshold depression and future major depression. A baseline meta-analysis was conducted using the inverse variance heterogeneity method to calculate the incidence rate ratio (IRR) of major depression among people with subthreshold depression relative to non-depressed controls. Subgroup analyses were conducted to investigate whether IRR estimates differed between studies categorised by age group or sample type. Sensitivity analyses were also conducted to test the robustness of baseline results to several sources of study heterogeneity, such as the case definition for subthreshold depression.
Data from 16 studies (n = 67 318) revealed that people with subthreshold depression had an increased risk of developing major depression (IRR = 1.95, 95% confidence interval 1.28–2.97). Subgroup analyses estimated similar IRRs for different age groups (youth, adults and the elderly) and sample types (community-based and primary care). Sensitivity analyses demonstrated that baseline results were robust to different sources of study heterogeneity.
The results of this study support the scaling up of effective indicated prevention interventions for people with subthreshold depression, regardless of age group or setting.
Oropharyngeal squamous cell carcinoma is thought to rarely metastasise to bone. This study hypothesised that in p16-positive disease there is a significant incidence of bony metastasis.
This was an ambispective cohort review. All patients with oropharyngeal squamous cell carcinoma diagnosed and treated at one centre were included.
A total of 180 consecutive patients were identified over 5 years. Fifteen patients were excluded because of lack of p16 status, none of whom had bony metastasis. The final analysis included 165 patients: 48 (29.09 per cent) in the p16-negative group and 117 (70.91 per cent) in the p16-positive group. Ten patients (8.55 per cent) in the p16-positive group developed bony metastasis, compared with zero in the p16-negative group; this difference was statistically significant (p = 0.036).
Expression of p16 was associated with an increased incidence in bony metastasis in this cohort. This is the first study to explore this specific question.
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.
Does foreign aid enable or constrain elite capture of public revenues? Reflecting on prominent debates in the foreign aid literature, we examine whether recipient preferences are consistent with a view that foreign donors wield substantial control over the flow of aid dollars, making elite capture more difficult and mass benefits more likely. We compare elite and mass support for foreign aid versus government spending on development projects through a survey experiment with behavioral outcomes. A key innovation is a parallel experiment on members of the Ugandan national parliament and a representative sample of Ugandan citizens. For two actual aid projects, we randomly assigned different funders to the projects. Significant treatment effects reveal that members of parliament support government programs over foreign aid, whereas citizens prefer aid over government. Donor control also implies that citizens should favor foreign aid more and elites less as their perceptions of government clientelism and corruption increase. We explore this and report on other alternative mechanisms. Effects for citizens and elites are most apparent for those perceiving significant government corruption, suggesting that both sets of subjects perceive significant donor control over aid.
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
Visuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
Areas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients’ quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis.
Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis.
Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively).
Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.
Introduction/Innovation Concept: Inter-professional education (IPE) involves ‘occasions when two or more professions learn with, from and about each other to improve collaboration and the quality of care’. Current literature has found IPE to increase knowledge and skills, improve attitudes towards other professions, and to promote superior clinical outcomes. Health Canada has collaborated to form accreditation standards to support IPE in Canadian medical schools. The proposed educational innovation termed the ‘nursing shift,’ based out of Kelowna General Hospital’s Department of Emergency Medicine, in partnership with UBC’s Southern and Island Medical Programs, endeavors to enhance IPE in our institution. Methods: This nursing shift was first trialed with third year medical students as a pilot rotation beginning in March of 2016. Based on overwhelmingly positive results obtained from narrative feedback, a formal rotation with the same structure will be implemented in the form of a prospective cohort study with 48 medical students from two UBC sites. One group will attend a nursing shift, while the other group will complete the standard emergency medicine rotation without this nursing shift. Impact will be measured using a mixed-method analysis where students will be asked to provide both quantitative feedback in the form of a questionnaire, and qualitative feedback in the form of a narrative response. The primary outcome will be quantitative score differences between the groups of students, and the secondary outcome will be qualitative results for those who completed the nursing shift. Curriculum, Tool, or Material: The innovative educational concept consists of an 8-hour nursing shift where medical students spend the first 4 hours at triage with a nurse learning about patient intake. The remaining 4 hours are in the emergency department where students collaborate with a nurse on a number of tasks including preparing and administering medications, starting intravenous lines, and inserting Foley catheters. Conclusion: Healthcare systems are shifting to a more collaborative team oriented approach, and IPE has been shown to prepare students for this changing workplace. We seek to understand third year medical students’ experience of the nursing shift, and to evaluate any changes in attitudes towards inter-professional collaboration after engaging in this intervention. Evaluation of this novel implementation will enable us to assess and optimize the nursing shift, and if it is well received, encourage widespread adoption.
Color-magnitude diagrams reaching from the giant branches to Vlim ~ 27.0, or about three magnitudes fainter than the turnoff, have been obtained in V and I with WFPC2 on HST for NGC 2419, Pal 3, Pal 4 and Eridanus, whose relative ages are discussed.
HST V, I color-magnitude diagrams (CMDs) of four outer-halo clusters, NGC 2419, Pa13, Pal4 and Eridanus, provide insight into the relative ages of old star clusters throughout the 200 kpc diameter volume sampled, and thus into the formation epoch of the Milky Way galaxy.
Introduction: Point of care ultrasound (PoCUS) provides invaluable information during resuscitation efforts in cardiac arrest by determining presence/absence of cardiac activity and identifying reversible causes such as pericardial tamponade. There is no agreed guideline on how to safely and effectively incorporate PoCUS into the advanced cardiac life support (ACLS) algorithm. We consider that a consensus-based priority checklist using a “4 F’s” approach (Fluid; Form; Function; Filling), would provide a better algorithm during ACLS. Methods: The ultrasound subcommittee of the Australasian College for Emergency Medicine (ACEM) drafted a checklist incorporating PoCUS into the ACLS algorithm. This was further developed using the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. A modified Delphi tool was developed to reach an international consensus on how to integrate ultrasound into cardiac arrest algorithms for emergency department patients. Results: Consensus was reached following 3 rounds. The agreed protocol focuses on the timing of PoCUS as well as the specific clinical questions. Core cardiac windows performed during the rhythm check pause in chest compressions are the sub-xiphoid and parasternal cardiac views. Either view should be used to detect pericardial fluid, as well as examining ventricular form (e.g. right heart strain) and function, (e.g. asystole versus organized cardiac activity). Supplementary views include lung views (for absent lung sliding in pneumothorax and for pleural fluid), and IVC views for filling. Additional ultrasound applications are for endotracheal tube confirmation, proximal leg veins for DVT, or for sources of blood loss (AAA, peritoneal/pelvic fluid). Conclusion: The authors hope that this process will lead to a consensus-based SHoC-cardiac arrest guideline on incorporating PoCUS into the ACLS algorithm.
The Full-sky Astrometric Mapping Explorer (FAME) is designed to perform an all-sky, astrometric survey with unprecedented accuracy. It will create a rigid astrometric catalog of 4 × 107 stars with 5 < mV < 15. For bright stars, 5 < mV < 9, FAME will determine positions and parallaxes accurate to < 50 μas, with proper motion errors < 50 μas/yr. For fainter stars, 9 < mV < 15, FAME will determine positions and parallaxes accurate to < 500 μas, with proper motion errors < 500 μas/yr. It will also collect photometric data on these 4 × 107 stars in four Sloan Digital Sky Survey colors. NASA selected FAME to be one of five MIDEX missions funded for a concept study. In October 1999, NASA selected FAME for launch in 2004 as the MIDEX-4 mission in its Explorer program.
People with severe mental illness (SMI) have high rates of chronic disease and premature death.
To explore the strength of evidence for interventions to reduce risk of mortality in people with SMI.
In a meta-review of 16 systematic reviews of controlled studies, mortality was the primary outcome (8 reviews). Physiological health measures (body mass index, weight, glucose levels, lipid profiles and blood pressure) were secondary outcomes (14 reviews).
Antipsychotic and antidepressant medications had some protective effect on mortality, subject to treatment adherence. Integrative community care programmes may reduce physical morbidity and excess deaths, but the effective ingredients are unknown. Interventions to improve unhealthy lifestyles and risky behaviours can improve risk factor profiles, but longer follow-up is needed. Preventive interventions and improved medical care for comorbid chronic disease may reduce excess mortality, but data are lacking.
Improved adherence to pharmacological and physical health management guidelines is indicated.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.