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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.
We present an indentation-scope that interfaces with confocal microscopy, enabling direct observation of the three-dimensional (3D) microstructural response of coatings on substrates. Using this method, we compared microns-thick polymer coatings on glass with and without silica nanoparticle filler. Bulk force data confirmed the >30% modulus difference, while microstructural data further revealed slip at the glass-coating interface. Filled coatings slipped more and about two times faster, as reflected in 3D displacement and von Mises strain fields. Overall, these data indicate that silica-doping of coatings can dramatically alter adhesion. Moreover, this method compliments existing theoretical and modeling approaches for studying indentation in layered systems.
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.
The study aim was to establish and quantify suicide risk following acute admissions for all major physical illnesses, for confirmatory purposes, from two independent information sources from different countries.
Record linkage of inpatient and death certificate data for 11 004 389 acute admissions for physical illnesses in England and 713 496 in Wales. The main outcome measure was standardised mortality ratios (SMRs) for suicide at 1 year following discharge from hospital.
There were 1781 suicides within 1 year of discharge in England (SMR = 1.7; 95% = 1.6–1.8) and 131 in Wales (SMR = 2.0; 1.7–2.3). Of 48 major physical illnesses that were associated with at least eight suicides in either country, there was high consistent suicide mortality (significant SMR >3) in both countries for constipation (SMR = 4.1 in England, 7.5 in Wales), gastritis (4.4 and 4.9) and upper gastrointestinal bleeding (3.4 and 4.5). There was high suicide mortality in one country for alcoholic liver disease, other liver disease and chronic pancreatitis; for epilepsy and Parkinson's disease; for diabetes, hypoglycaemia and hypo-osmolality & hyponatraemia; and for pneumonia, back pain and urinary tract infections.
There is little or no increased suicide mortality following acute admissions for most physical illnesses. Much of the increased suicide mortality relates to gastrointestinal disorders that are often alcohol related or specific chronic conditions, which may be linked to side effects from certain therapeutic medications. Acute hospital admissions for physical illnesses may therefore provide an opportunity for targeted suicide prevention among people with certain conditions, particularly alcohol related disorders.
The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.
OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.
EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).
Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The Australian dairy herd size has doubled over the last 20 years substantially increasing the time that farmers require for individual animal attention to monitor and intervene with events such as calving. Technology will help focus this limited labour resource on individual cows that require assistance. The objective of this experiment was to first determine the profiles of rumination duration and level of activity as determined by sensors between, and within, days around calving and second to use these data to predict the day of calving for pasture-based dairy cows. After 2 weeks from the expected calving date, 27 cows were fitted with SCR HR LD Tags, located in 40×90 m2 paddock and offered ad libitum oaten hay and 2 kg grain-based concentrate/cow per day until calving. Hourly activity and rumination data for each cow, as determined by the SCR tags, were fitted with linear mixed models and all parameters were estimated using restricted maximum likelihood. Rumination duration decreased by 33% over the day prior and the day of calving, with the decline in rumination duration starting the day prepartum. Activity levels were maintained prepartum but increased in the days postpartum. The day of calving was recorded and used to determine the gold standard positive (the day before calving) and negative (all other) dates. A threshold rumination level of 0.9 (decline in rumination duration of 10%) gave the optimal combination of 70% sensitivity and 70% specificity. This experiment shows the potential to use rumination duration to predict the day of calving and the opportunity to use sensor data to monitor animal health.
Caregivers of patients with advanced cancer experience physical and emotional strain that can raise their own risk for morbidity and mortality. This analysis was performed to determine whether ENABLE II, a patient-focused palliative care intervention that increased patients' quality of life, reduced symptom intensity, and lowered depressed mood compared to usual care, would affect caregiver burden.
Caregivers of patients with advanced cancer from the parent study completed a caregiver burden scale and patients completed quality of life, symptom intensity, and depressed mood measures. Data were collected at baseline, 1 month, and every 3 months thereafter until patient death or the study ended. Decedents' caregivers were asked to complete an after-death interview regarding the quality of care that the patient received.
There were no significant differences in caregiver burden between intervention and usual care conditions. Follow-up analyses showed that higher caregiver objective burden and stress burden were related to lower patient quality of life, higher symptom intensity, and higher depressed mood. Caregivers who perceived that patients had unmet needs at end of life reported higher objective burden, and those who perceived that patients were not treated with respect reported higher demand burden.
Significance of results:
The results indicate that a successful patient-focused intervention did not have a similar beneficial effect on caregiver burden. Future interventions should focus on caregivers as well as patients, with particular attention to caregivers' perceptions of patient care, and seek to change both negative and positive effects of informal caregiving.
Detection and tracking of stem cell state are difficult due to insufficient means for rapidly screening cell state in a noninvasive manner. This challenge is compounded when stem cells are cultured in aggregates or three-dimensional (3D) constructs because living cells in this form are difficult to analyze without disrupting cellular contacts. Multiphoton laser scanning microscopy is uniquely suited to analyze 3D structures due to the broad tunability of excitation sources, deep sectioning capacity, and minimal phototoxicity but is throughput limited. A novel multiphoton fluorescence excitation flow cytometry (MPFC) instrument could be used to accurately probe cells in the interior of multicell aggregates or tissue constructs in an enhanced-throughput manner and measure corresponding fluorescent properties. By exciting endogenous fluorophores as intrinsic biomarkers or exciting extrinsic reporter molecules, the properties of cells in aggregates can be understood while the viable cellular aggregates are maintained. Here we introduce a first generation MPFC system and show appropriate speed and accuracy of image capture and measured fluorescence intensity, including intrinsic fluorescence intensity. Thus, this novel instrument enables rapid characterization of stem cells and corresponding aggregates in a noninvasive manner and could dramatically transform how stem cells are studied in the laboratory and utilized in the clinic.
During 2003, a cluster of initially unexplained pneumonia cases (two fatal) occurred in patients aged <50 years in a British city. Routine culture tests were inconclusive, however, pneumococcal infection was suspected and the putative outbreak was investigated using non-culture methods. Clinical samples from ten patients were tested by pneumococcal polymerase chain reaction (PCR) and multi-locus sequence typing (MLST), or Binax NOW® pneumococcal urine antigen test and serotype-specific enzyme-linked immunosorbent assay (ELISA). Lung samples from the deceased patients were PCR positive and yielded different MLST types. Two patients in one family group were serotype 1 pneumococcal antigen positive. Two further patients were serotype 1 antigen positive, and one serotype 4 positive. Two antigen-positive cases were also serum PCR positive. Non-culture methods confirmed the disease aetiology in six cases. Serotype and MLST results showed no single outbreak, but a family cluster of cases in a high background of pneumococcal pneumonia, providing important epidemiological data that would not otherwise have been available.
The 2001/02 austral summer was the warmest summer on record in Taylor Valley, Antarctica, (∼78° S) since continuous records of temperature began in 1985. The highest stream-flows ever recorded in the Onyx River, Wright Valley, were also recorded that year (the record goes back to the 1969/70 austral summer). In early January 2002, a groundwater seep was observed flowing in the southwest portion of Taylor Valley. This flow has been named ‘Wormherder Creek’ (WHC) and represents an unusual event, probably occurring on a decadal time-scale. The physical characteristics of this feature suggest that it may have flowed at other times in the past. Other groundwater seeps, emanating from the north-facing slope of Taylor Valley, were also observed. Little work has been done previously on these very ephemeral seeps, and the source of water is unknown. These features, resembling recently described features on Mars, represent the melting of subsurface ice. The Martian features have been interpreted as groundwater seeps. In this paper we compare the chemistry of the WHC groundwater seep to that of the surrounding streams that flow every austral summer. The total dissolved solids content of WHC was ∼6 times greater than that of some nearby streams. The Na : Cl and SO4 : Cl ratios of the seep waters are higher than those of the streams, but the Mg : Cl and HCO3 : Cl ratios are lower, indicating different sources of solutes to the seeps compared to the streams. The enrichment of Na and SO4 relative to Cl may suggest significant dissolution of mirabilite within the previously unwetted soil. The proposed occurrence of abundant mirabilite in higher-elevation soils of the dry valley region agrees with geochemical models developed, but not tested, in the late 1970s. The geochemical data demonstrate that these seeps could be important in ‘rinsing’ the soils by dissolving and redistributing the long-term accumulation of salts, and perhaps improving habitat suitability for soil biota. The H4SiO4 concentration is 2–3 times greater in WHC than in the surrounding streams, indicating a large silicate-weathering component in the seep waters.
Porous SiLK resin is an ultra-low-k interlayer dielectric (ILD) material designed to meet the needs of the 65 nm technology node and beyond. In early 2002, the porous SiLK resin formulation was defined and scaled up, facilitating the tight monitoring and control of key properties, including pore size distribution, over several lots of material. The film processing kinetics are now well understood and a wide process window exists which ensures optimum pore morphology and pore size distribution. Thermal cycling of films demonstrates no effect on pore morphology or dielectric constant. The material has been designed to minimize the impact of CTE mismatch at high temperature, which challenged the integration of some previous generations of SiLK and porous SiLK dielectric resins. The discrete, closed-cell pore geometry is well characterized and enables the extendibility of process module development from SiLK resin technology to porous SiLK resin. Concurrent with the scale up efforts, advancements in minimizing both cure time and temperature simultaneously, as well as significant improvements in pore size and pore size distribution, have been achieved. The cure and porogen burn out time has been reduced by 50% or greater, and the temperature has been reduced to 370°C. The pore size has been reduced by ∼35%, and the pore size distribution has been narrowed by ∼40%. These advancements have resulted in the introduction of porous SiLK T resin, with a dielectric constant of k = 2.4 and a recommended cure temperature of 370°C, and the introduction of porous SiLK U resin, with a mean pore diameter of ∼5 nm and a dielectric constant of k = 2.2.