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The aim of the Avera Twin Register (ATR) is to establish a prospective longitudinal repository of twins, multiples, siblings and family members’ biological samples to study environmental and genetic influences on health and disease. Also, it is our intention to contribute to international genome-wide association study (GWAS) twin consortia when appropriate sample size is achieved within the ATR. The ATR is young compared with existing registers and continues to collect a longitudinal repository of biological specimens, survey data and health information. Data and biological specimens were originally collected via face-to-face appointments or the postal department and consisted of paper-informed consents and questionnaires. Enrollment of the ATR began on May 18, 2016 and is located in Sioux Falls, South Dakota, a rural and frontier area in the Central United States with a regional population of approximately 880,000. The original target area for the ATR was South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota and Nebraska. The ATR has found a need to expand that area based on twin and multiple siblings who live in various areas surrounding these states. A description of the state of the ATR today and its transition to online data collection and informed consent will be presented. The ATR collects longitudinal data on lifestyle, including diet and activity levels, aging, plus complex traits and diseases. All twins and multiples participating in the ATR are genotyped on the Illumina Global Screening Array and receive zygosity results.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
The Avera Twin Register (ATR) aims to study environmental and genetic influences on health and disease using a longitudinal repository of biological specimens, survey data, and health information provided by multiples and their family members. The ATR is located in Sioux Falls, South Dakota, which is a rural and frontier area in the Midwestern United States with a density of four people per square kilometer. The target area of the ATR is South Dakota and the four surrounding states: Minnesota, Iowa, North Dakota, and Nebraska. Enrollment of twins and higher-order multiples of all ages and their family members started on May 18, 2016. A description of the first 13 months of enrollment in this longitudinal register will be provided. The ATR will collect longitudinal data on lifestyle, including diet and activity levels, aging, complex traits, and diseases. Upon registration, all participants are genotyped on the Illumina Global Screening Array (GSA) and twins and higher order multiples receive information on their zygosity. The ATR aims to contribute to large international GWAS consortia and collaborates closely with the Netherlands Twin Register, allowing for the comparison of collected data and analyses of results. In addition, the ATR will address twin-specific questions.
We assess the runoff and surface mass balance (SMB) of the Greenland ice sheet in the Nuuk region (southwest) using output of two regional climate models (RCMs) evaluated by observations. The region encompasses six glaciers that drain into Godthåbsfjord. RCM data (1960–2012) are resampled to a high spatial resolution to include the narrow (relative to the native grid spacing) glacier trunks in the ice mask. Comparing RCM gridded results with automatic weather station (AWS) point measurements reveals that locally models can underestimate ablation and overestimate accumulation by up to tens of per cent. However, comparison with lake discharge indicates that modelled regional runoff totals are more accurate. Model results show that melt and runoff in the Nuuk region have doubled over the past two decades. Regional SMB attained negative values in recent high-melt years. Taking into account frontal ablation of the marine-terminating glaciers, the region lost 10–20 km3 w.e. a–1 in 2010–12. If 2010 melting prevails during the remainder of this century, a low-end estimate of sea-level rise of 5 mm is expected by 2100 from this relatively small section (2.6%) of the ice sheet alone.
Individuals with anxiety disorders exhibit a ‘vigilance-avoidance’ pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as ‘threat bias’. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces.
Subjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging.
Adolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset.
Threat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.
Clinical and population-based studies report increased prevalence of autism spectrum disorders (ASD) in individuals with anorexia nervosa and in their relatives. No nationwide study has yet been published on co-occurrence of these disorders.
To investigate comorbidity of ASD in individuals with anorexia nervosa, and aggregation of ASD and anorexia nervosa in their relatives.
In Danish registers we identified all individuals born in 1981–2008, their parents, and full and half siblings, and linked them to data on hospital admissions for psychiatric disorders.
Risk of comorbidity of ASD in probands with anorexia nervosa and aggregation of ASD in families of anorexia nervosa probands were increased. However, the risk of comorbid and familial ASD did not differ significantly from comorbid and familial major depression or any psychiatric disorder in anorexia nervosa probands.
We confirm aggregation of ASD in probands with anorexia nervosa and in their relatives; however, the relationship between anorexia nervosa and ASD appears to be non-specific.
There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.
Individual lifestyle factors have been associated with lifestyle diseases and premature mortality by an accumulating body of evidence. The impact of a combination of lifestyle factors on mortality has been investigated in several studies, but few have applied a simple index taking national guidelines into account. The objective of the present prospective cohort study was to investigate the combined impact of adherence to five lifestyle factors (smoking, alcohol intake, physical activity, waist circumference and diet) on all-cause, cancer and cardiovascular mortality based on international and national health recommendations. A Cox proportional hazards model was used to estimate hazard ratios (HR) with 95 % CI. During a median follow-up of 14 years, 3941 men and 2827 women died. Among men, adherence to one additional health recommendation was associated with an adjusted HR of 0·73 (95 % CI 0·71, 0·75) for all-cause mortality, 0·74 (95 % CI 0·71, 0·78) for cancer mortality and 0·70 (95 % CI 0·65, 0·75) for cardiovascular mortality. Among women, the corresponding HR was 0·72 (95 % CI 0·70, 0·75) for all-cause mortality, 0·76 (95 % CI 0·73, 0·80) for cancer mortality and 0·63 (95 % CI 0·57, 0·70) for cardiovascular mortality. In the present study, adherence to merely one additional health recommendation had a protective effect on mortality risk, indicating a huge potential in enhancing healthy lifestyle behaviours of the population.
This longitudinal study considers externalizing behavior problems from ages 5 to 27 (N = 585). Externalizing problem ratings by mothers, fathers, teachers, peers, and self-report were modeled with growth curves. Risk and protective factors across many different domains and time frames were included as predictors of the trajectories. A major contribution of the study is in demonstrating how heterotypic continuity and changing measures can be handled in modeling changes in externalizing behavior over long developmental periods. On average, externalizing problems decreased from early childhood to preadolescence, increased during adolescence, and decreased from late adolescence to adulthood. There was strong nonlinear continuity in externalizing problems over time. Family process, peer process, stress, and individual characteristics predicted externalizing problems beyond the strong continuity of externalizing problems. The model accounted for 70% of the variability in the development of externalizing problems. The model's predicted values showed moderate sensitivity and specificity in prediction of arrests, illegal drug use, and drunk driving. Overall, the study showed that by using changing, developmentally relevant measures and simultaneously taking into account numerous characteristics of children and their living situations, research can model lengthy spans of development and improve predictions of the development of later, severe externalizing problems.
Previous research has found associations but not established mechanisms of developmental linkage between language ability and inattentive–hyperactive (I-H) behavior problems. The present study examined whether self-regulation mediates the effect of language ability on later I-H behavior problems among young children (N = 120) assessed at 30, 36, and 42 months of age. Cross-lagged panel models tested the direction of effect between language ability and self-regulation and longitudinal effects of language ability on later I-H problems mediated by self-regulation. Language ability was measured by children's scores on the receptive and expressive language subtests of the Differential Ability Scales. Self-regulation was measured by three behavioral tasks requiring inhibitory control. I-H problems were reported by parents and secondary caregivers. Language ability predicted later self-regulation as measured by all three tasks. There was no association, however, between self-regulation and later language ability, suggesting that the direction of effect was stronger from language ability to later self-regulation. Moreover, the effect of language ability on later I-H behavior problems was mediated by children's self-regulation in one of the tasks (for secondary caregivers' but not parents' ratings). Findings suggest that language deficits may explain later I-H behavior problems via their prediction of poorer self-regulatory skills.
Ventricular septal defects are normally closed in early childhood, and post-surgically the patients are considered as healthy and fit as their peers. However, data are inconsistent. We exercise-tested a cohort of ventricular septal defect-operated patients and a group of matched controls to evaluate long-term physical fitness.
Cardiopulmonary exercise capacity was tested on an ergometer cycle in 30 patients and 30 healthy age and gender-matched controls. Pulmonary ventilation and gas exchange were simultaneously measured breath-by-breath with Jaeger MasterScreen CPX® (CareFusion, San Diego, United States of America). During the test session, respiratory gas exchange was measured along with heart rate, blood pressure, and electrocardiogram. The endpoints were peak oxygen uptake, maximal workload, and ventilatory anaerobic threshold. The International Physical Activity Questionnaire and the SF-36 were applied for Health-Related Quality-of-Life assessment.
Ventricular septal defect-operated adults had a markedly lower peak oxygen uptake: mean 38.0(±8.2 ml O2/kg/minute) versus 47.9(±6.5 ml O2/kg/minute) in controls, p<0.01. Furthermore, ventilatory anaerobic threshold was impaired in ventricular septal defect patients: mean 25.3(±7.8 ml O2/kg/minute) versus 35.2(±7.7 ml O2/kg/minute) in controls, p<0.01. Maximal workload was reduced: mean 3.3(±0.7 W/kg) versus 4.0(±0.5 W/kg) in the control group, p<0.01. Lastly, ventricular septal defect patients had a significantly lower peak heart rate: mean 182(±8.8 beats/minute) versus 188(±9.0 beats/minute) in controls, p=0.03. Regarding Health-Related Quality of Life, the ventricular septal defect group had significantly lower scores in physical functioning, role physical, and social functioning.
Young adults with a surgically closed ventricular septal defect had a markedly reduced cardiopulmonary exercise capacity and a lower peak heart rate compared with controls.
To describe the frequency of use of all types of urinary catheters, including but not limited to indwelling catheters, as well as positive cultures associated with the various types. We also determined the accuracy of catheter-days reporting at our institution.
Prospective, observational trial based on patient-level review of the electronic medical record. Chart review was compared with standard methods of catheter surveillance and reporting by infection control personnel.
Ten internal medicine and 5 long-term care wards in 2 tertiary care Veterans Affairs hospitals in Texas from July 2010 through June 2011.
The study included 7,866 inpatients.
Measurements included patient bed-days; days of use of indwelling, external, suprapubic, and intermittent urinary catheters; number of urine cultures obtained and culture results; and infection control reports of indwelling catheter-days.
We observed 7,866 inpatients with 128,267 bed-days on acute medicine and extended care wards during the study. A urinary catheter was used on 36.9% of the total bed-days observed. Acute medicine wards collected more urine cultures per 1,000 bed-days than did the extended care wards (75.9 and 10.4 cultures per 1,000 bed-days, respectively; P < .0001 ). Catheter-days were divided among indwelling-catheter-days (47.8%), external-catheter-days (48.4%), and other (intermittent- and suprapubic-catheter-days, 3.8%). External catheters contributed to 376 (37.3%) of the 1,009 catheter-associated positive urine cultures. Urinary-catheter-days reported to the infection control department missed 20.1% of the actual days of indwelling catheter use, whereas 12.0% of their reported catheter-days were false.
Urinary catheter use was extremely common. External catheters accounted for a large portion of catheter-associated bacteriuria, and standard practices for tracking urinary-catheter-days were unreliable.
The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life.
The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2·04 (95% confidence interval 1·43–2·91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.
The gettering behavior of Cu and Fe was investigated in CZ silicon containing both internal-gettering sites in the bulk due to SiO2 precipitation and a device-side layer of cavities formed by He ion implantation and annealing. The objective was to quantify the effectiveness of impurity gettering at cavities relative to the widely used internal-gettering process. Both rapid thermal anneals and furnace anneals were used during the gettering sequences to reveal transient effects as well as the final, thermodynamically-equilibrated condition. For temperatures of 700, 800 and 850°C, the cavity gettering was observed to dominate the internal gettering as indicated both by the number of gettered atoms in the cavities and the residual solution concentration in the device region. The results are interpreted in detail by numerically solving the diffusion equation with sink-related source terms based on earlier, fundamental studies of the underlying mechanisms of internal and cavity gettering.
Serial assessments are commonplace in neuropsychological practice and used to document cognitive trajectory for many clinical conditions. However, true change scores may be distorted by measurement error, repeated exposure to the assessment instrument, or person variables. The present study provides reliable change indices (RCI) for the Boston Naming Test, derived from a sample of 844 cognitively normal adults aged 56 years and older. All participants were retested between 9 and 24 months after their baseline exam. Results showed that a 4-point decline during a 9–15 month retest period or a 6-point decline during a 16–24 month retest period represents reliable change. These cutoff values were further characterized as a function of a person's age and family history of dementia. These findings may help clinicians and researchers to characterize with greater precision the temporal changes in confrontation naming ability. (JINS, 2012, 18, 375–378)
Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73–94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection – even under continuous within-partnership exposure – appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.