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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.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
Less than half of stool samples from people symptomatic with infectious intestinal disease (IID) will identify a causative organism. A secondary data analysis was undertaken to explore whether symptomology alone could be used to make inferences about causative organisms. Data were utilised from the Second Study of Infectious Intestinal Disease in the Community. A total of 844 cases were analysed. Few symptoms differentiated individual pathogens, but grouping pathogens together showed that viral IID was more likely when symptom onset was in winter (odds ratio (OR) 2.08, 95% confidence interval (CI) 1.16–3.75) or spring (OR 1.92, 95% CI 1.11–3.33), the patient was aged under 5 years (OR 3.63, 95% CI 2.24–6.03) and there was loss of appetite (OR 2.19, 95% CI 1.29–3.72). The odds of bacterial IID were higher with diarrhoea in the absence of vomiting (OR 3.54, 95% CI 2.37–5.32), diarrhoea which persisted for >3 days (OR 2.69, 95% CI 1.82–3.99), bloody diarrhoea (OR 4.17, 95% CI 1.63–11.83) and fever (OR 1.67, 95% CI 1.11–2.53). Symptom profiles could be of value to help guide clinicians and public health professionals in the management of IID, in the absence of microbiological confirmation.
The incidence of deep neck space abscesses, which can result in significant morbidity and mortality, is rising. The aetiology is thought to be dental. However, this study suggests a reduction in tonsillectomies may be associated with the rise.
In a retrospective cohort study, patients were identified by a clinical code within one hospital over 10 years. Evidence of preceding infection source, management, lifestyle risks, comorbidities and demographics were extracted.
Fifty-two patients were included: 23 (44 per cent) had concurrent or recent tonsillitis; 11 (21 per cent) had poor dental hygiene; 22 (42 per cent) were smokers; and 9 (17 per cent) had diabetes. The incidence of deep neck space abscess cases increased from 1 in 2006, to 15 in 2015 (correlation value 0.9; p = 0.00019).
The incidence of deep neck space abscess cases is increasing. Risk factors include tonsillitis, smoking and dental infection. This paper adds to the growing evidence that deep neck space abscesses are increasingly related to tonsillitis, and questions whether the threshold for tonsillectomy has been raised too high.
Household surveys are one of the most commonly used tools for generating insight into rural communities. Despite their prevalence, few studies comprehensively evaluate the quality of data derived from farm household surveys. We critically evaluated a series of standard reported values and indicators that are captured in multiple farm household surveys, and then quantified their credibility, consistency and, thus, their reliability. Surprisingly, even variables which might be considered ‘easy to estimate’ had instances of non-credible observations. In addition, measurements of maize yields and land owned were found to be less reliable than other stationary variables. This lack of reliability has implications for monitoring food security status, poverty status and the land productivity of households. Despite this rather bleak picture, our analysis also shows that if the same farm households are followed over time, the sample sizes needed to detect substantial changes are in the order of hundreds of surveys, and not in the thousands. Our research highlights the value of targeted and systematised household surveys and the importance of ongoing efforts to improve data quality. Improvements must be based on the foundations of robust survey design, transparency of experimental design and effective training. The quality and usability of such data can be further enhanced by improving coordination between agencies, incorporating mixed modes of data collection and continuing systematic validation programmes.
In low- and middle-income countries (LMIC) in general and sub-Sahara African (SSA) countries in particular, there is both a large treatment gap for mental disorders and a relative paucity of empirical evidence about how to fill this gap. This is more so for severe mental disorders, such as psychosis, which impose an additional vulnerability for human rights abuse on its sufferers. A major factor for the lack of evidence is the few numbers of active mental health (MH) researchers on the continent and the distance between the little evidence generated and the policy-making process.
The Partnership for Mental Health Development in Africa (PaM-D) aimed to bring together diverse MH stakeholders in SSA, working collaboratively with colleagues from the global north, to create an infrastructure to develop MH research capacity in SSA, advance global MH science by conducting innovative public health-relevant MH research in the region and work to link research to policy development. Participating SSA countries were Ghana, Kenya, Liberia, Nigeria and South Africa. The research component of PaM-D focused on the development and assessment of a collaborative shared care (CSC) program between traditional and faith healers (T&FHs) and biomedical providers for the treatment of psychotic disorders, as a way of improving the outcome of persons suffering from these conditions. The capacity building component aimed to develop research capacity and appreciation of the value of research in a broad range of stakeholders through bespoke workshops and fellowships targeting specific skill-sets as well as mentoring for early career researchers.
In the research component of PaM-D, a series of formative studies were implemented to inform the development of an intervention package consisting of the essential features of a CSC for psychosis implemented by primary care providers and T&FHs. A cluster randomised controlled trial was next designed to test the effectiveness of this package on the outcome of psychosis. In the capacity-building component, 35 early and mid-career researchers participated in the training workshops and several established mentor-mentee relationships with senior PaM-D members. At the end of the funding period, 60 papers have been published and 21 successful grant applications made.
The success of PaM-D in energising young researchers and implementing a cutting-edge research program attests to the importance of partnership among researchers in the global south working with those from the north in developing MH research and service in LMIC.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
Grommet insertion is a common surgical procedure in children. Long waiting times for grommet insertion are not unusual. This project aimed to streamline the process by introducing a pathway for audiologists to directly schedule children meeting National Institute for Health and Care Excellence Clinical Guideline 60 (‘CG60’) for grommet insertion.
Method and results
A period from June to November 2014 was retrospectively audited. Mean duration between the first audiology appointment and grommet insertion was 294.5 days (median = 310 days). Implementing the direct-listing pathway reduced the duration between first audiology appointment and grommet insertion (mean = 232 days; median = 231 days). There has been a reduction in the time between the first audiology appointment and surgery (mean difference of 62.5 days; p = 0.024), and a reduction in the time between second audiology appointment and surgery (28 days; p = 0.009).
Direct-listing pathways for grommet insertion can reduce waiting times and expedite surgery. Implementation involves a simple alteration of current practice, adhering to National Institute for Health and Care Excellence Clinical Guideline 60. The ultimate decision regarding surgery still rests with ENT specialists.
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.
Twenty-seven species and two subspecies of Ficus are reported from one study site in central Africa. Characters for identification are explained. An identification key, illustrations, descriptions and habitats are provided. The species-level diversity of Ficus in tropical forests is discussed.
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.
To analyze whether electronically available comorbid conditions are risk factors for Centers for Disease Control and Prevention (CDC)-defined, hospital-onset Clostridium difficile infection (CDI) after controlling for antibiotic and gastric acid suppression therapy use.
Patients aged ≥18 years admitted to the University of Maryland Medical Center between November 7, 2015, and May 31, 2017.
Comorbid conditions were assessed using the Elixhauser comorbidity index. The Elixhauser comorbidity index and the comorbid condition components were calculated using the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes extracted from electronic medical records. Bivariate associations between CDI and potential covariates for multivariable regression, including antibiotic use, gastric acid suppression therapy use, as well as comorbid conditions, were estimated using log binomial multivariable regression.
After controlling for antibiotic use, age, proton-pump inhibitor use, and histamine-blocker use, the Elixhauser comorbidity index was a significant risk factor for predicting CDI. There was an increased risk of 1.26 (95% CI, 1.19–1.32) of having CDI for each additional Elixhauser point added to the total Elixhauser score.
An increase in Elixhauser score is associated with CDI. Our study and other studies have shown that comorbid conditions are important risk factors for CDI. Electronically available comorbid conditions and scores like the Elixhauser index should be considered for risk-adjustment of CDC CDI rates.
We assessed various locations and frequency of environmental sampling to maximize information and maintain efficiency when sampling for Acinetobacter baumannii. Although sampling sites in closer proximity to the patient were more likely positive, to fully capture environmental contamination, we found value in sampling all sites and across multiple days.
We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events.
Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events.
There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19–2.1) and indirect (OR 1.51, 95% CI: 1.32–1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%.
The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.
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.