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TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King’s College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several ‘omic’ technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the ‘TwinsUK’ resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.
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.
Characterisation of genetic diversity in a large number of European pig populations has been undertaken with EC support. The populations sampled included local (rare) breeds, national varieties of the major international breeds, commercial lines and the Chinese Meishan breed. A second phase of the project will sample a further 50 Chinese breeds. Neutral genetic markers (AFLP and microsatellites), with individual or bulk typing, were used and compared.
DNA from 59 European pig populations was extracted on samples of about 50 individuals per population. Individuals were typed for 50 microsatellites and for 148 AFLP bands. A subset of 25 populations was typed for 20 microsatellites on pools of DNA. Allele frequencies were estimated by direct allele counting for the co-dominant markers. Frequencies of AFLP negative alleles (absent bands) were obtained by taking the square root of absent band frequencies. Within-breed variability was summarised using standard statistics: expected and observed heterozygosity, mean observed and effective numbers of alleles, and F statistics. Between-breed diversity analysis was based on a bootstrapped Neighbor-Joining (NJ) tree derived from Reynolds distances (DR). The standard distance of Nei (DS) was also calculated.
Rapeseed meal is a common protein supplement in ruminant diets that is characterized by high rumen protein degradability (Bertilsson et al., 1994; Vanhatalo et al., 1995). Appropriate treatment can however reduce ruminal protein degradability and increase the efficiency of protein utilization. RaPass (UM Feeds Marketing, Burton on Trent, Staffs, UK) is a commercial rapeseed meal product that made using the Maillard reaction. This is the non-enzymatic browning reaction between proteins and reducing sugars that protects protein from rumen degradation. Release of the protein at abomasal pH allows the peptide chains to be digested at an efficiency similar to that of untreated rapeseed meal (Moss et al 2000). Cows fed rapeseed meal that was treated to increase the rumen undegradable protein (RUP) content have been reported to perform better than those fed untreated rapeseed meal (Bertilsson et al., 1994). This study evaluated the potential of using RaPass as a protein supplement in dairy cow rations.
To characterise and identify nationwide trends in suicide-related emergency department (ED) visits in the USA from 2006 to 2013.
We used data from the Nationwide Emergency Department Sample (NEDS) from 2006 to 2013. E-codes were used to identify ED visits related to suicide attempts and self-inflicted injury. Visits were characterised by factors such as age, sex, US census region, calendar month, as well as injury severity and mechanism. Injury severity and mechanism were compared between age groups and sex by chi-square tests and Wilcoxon rank-sum tests. Population-based rates were computed using US Census data.
Between 2006 and 2013, a total of 3 567 084 suicide attempt-related ED visits were reported. The total number of visits was stable between 2006 and 2013, with a population-based rate ranging from 163.1 to 173.8 per 100 000 annually. The frequency of these visits peaks during ages 15–19 and plateaus during ages 35–45, with a mean age at presentation of 33.2 years. More visits were by females (57.4%) than by males (42.6%); however, the age patterns for males and females were similar. Visits peaked in late spring (8.9% of all visits occurred in May), with a smaller peak in the fall. The most common mechanism of injury was poisoning (66.5%), followed by cutting and piercing (22.1%). Males were 1.6 times more likely than females to use violent methods to attempt suicide (OR = 1.64; 95% CI = 1.60–1.68; p < 0.001). The vast majority of patients (82.7%) had a concurrent mental disorder. Mood disorders were the most common (42.1%), followed by substance-related disorders (12.1%), alcohol-related disorders (8.9%) and anxiety disorders (6.4%).
The annual incidence of ED visits for attempted suicide and self-inflicted injury in the NEDS is comparable with figures previously reported from other national databases. We highlighted the value of the NEDS in allowing us to look in depth at age, sex, seasonal and mechanism patterns. Furthermore, using this large national database, we confirmed results from previous smaller studies, including a higher incidence of suicide attempts among women and individuals aged 15–19 years, a large seasonal peak in suicide attempts in the spring, a predominance of poisoning as the mechanism of injury for suicide attempts and a greater use of violent mechanisms in men, suggesting possible avenues for further research into strategies for prevention.
Background: The clinical identification of hippocampal sclerosis (HS) is important in predicting surgical outcomes in patients with temporal lobe epilepsy (TLE). In cases where gross hippocampal sclerosis is not identifiable clinically, a more detailed analysis of hippocampal subfields using ultra-high-field magnetic resonance imaging (MRI) may reveal areas of abnormality, which was the focus of our study. Methods: Patients (N=13) with drug-resistant TLE (9 no-HS, 4 HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes were studied between the two groups. In addition, radiological patient assessment at 7T was correlated with measured subfield changes. Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield losses in CA1 and CA4DG. Volumetry also uncovered subfield volume losses in 33% of no-HS patients, which had not been detected conventionally. Furthermore, 89% of no-HS patients showed abnormality (internal architecture or size) at 7T, identified by radiologists blinded to the patient’s initial classification. Conclusions: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T may be superior to conventional visual inspection by a neuroradiologist in the identification of hippocampal pathologies in TLE.
Background: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque. Methods: Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET. Results: NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04). Conclusion: NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.
This study provides a detailed description of the development of the gastrointestinal tract (GIT) of farmed red deer (Cervus elaphus) calves over the first 12 months of age. GIT development was measured using a combination of computerised tomography (CT) scanning and traditional slaughter plus dissection techniques. Red deer calves of a known birth date were randomly assigned to two treatment groups. A group of five animals were repeatedly CT scanned at 31, 63, 92, 135, 207, 275 and 351 days of age to identify GIT organs and determine their volume. From a group of 20 animals, subsets of four individuals were also scanned at corresponding ages (except 135 days of age). They were immediately euthanised and dissected after CT scanning to compare CT-scanned results with actual anatomical measurements. Individual organ weights were compared with their respective organ volumes determined by CT scanning and were found to have a strong, positive relationship. The combined rumen and reticulum (RR) CT-scanned volume was compared with its volume determined by the water-displacement technique and this also showed good correlation between the two techniques (R = 0.92). The allometric growth rates of organs, relative to animal live weight gains, in descending order, were the rumen, omasum, reticulum, abomasum, caecum blind sac, kidneys, spleen and liver. The red deer GIT was continuing to grow and develop when the last measurement was taken at 351 days of age. The greatest growth of the RR, when expressed in terms of empty weight, was between 31 and 92 days of age. Compared with sheep and cattle, it appears that the red deer have a similar or greater rate of RR development up until approximately 60 to 90 days of age; however, the final increments of GIT maturity in deer may take longer to complete, with the empty weight of the RR gaining 7.5 g/day between 275 and 351 days of age. CT scanning was validated in this study as a viable technique to follow GIT development in the same animals over time, and it provided novel information on allometric organ growth. The success of CT scanning highlights the potential future use of diagnostic imaging for GIT development studies.
Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.
Controlled incorporation of dopants into semiconductors nanowires is a critical step in tailoring their physical properties and hence for their utilization in future nano electronic devices. Recently, several studies addressing this issue revealed that dopant are inhomogeneously distributed in NWs grown by the popular CVD-VLS growth technique. The majority of those studies employed indirect characterization techniques which are sensitive to the active dopants only. In order to deepen our understanding of the incorporation mechanism a direct observation of the dopant chemical concentrations is required. In addition, the comparison between direct and indirect observations can shed some light on the dopant activation mechanisms in VLS grown NWs. In this study nanoprobe scanning Auger microscopy was employed to extract the longitudinal dopant distribution along P doped SiNWs. The effect of growth conditions and post-growth annealing on this distribution was studied and compared to previous studies which used indirect measurement techniques. In addition, dopant modulated segmented NWs were studied in order to distinguish the contribution of different mechanisms to the incorporation of dopants into VLS grown NWs.
Over the past decade, the field of nanotechnology has expanded, and the most heavily used nanoscale characterization/imaging techniques have been scanning probe microscopy (SPM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Although these high-resolution imaging techniques help visualize nanostructures, it is essential to understand the chemical nature of these materials and their growth mechanisms. Surface modifications in the first few nanometers can alter the bulk properties of these nanostructures, and conventional characterization techniques, including energy dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS) associated with SEM and TEM are not suited to detecting these surface modifications except in special, favorable specimens. A modern state-of-the-art scanning Auger electron spectroscopy (AES) instrument provides valuable elemental and chemical characterization of nanostructures with a lateral spatial resolution better than 10 nm and a depth resolution of a few nm. In this article we review the technique of scanning AES and highlight its unique analytical capabilities in the areas of nanotechnology, metallurgy, and semiconductors.
Measurements were made of the conductance of single crystal Au-doped Si and silicon-on-sapphire (SOS) during irradiation with 30 nsec ruby laser pulses. After the decay of the photoconductive response, the sample conductance is determined primarily by the thickness and conductivity of the molten layer. For the single crystal Au-doped Si, the solid-liquid interface velocity during recrystallization was determined from the current transient to be 2.5 m/sec for energy densities between 1.9 and 2.6 J/cm2, in close agreement with numerical simulations based on a thermal model of heat flow. SOS samples showed a strongly reduced photoconductive response, allowing the melt front to be observed also. For complete melting of a 0.4 μm Si layer, the regrowth velocity was 2.4 m/sec.
Members of the Ruddlesden-Popper system, La2Ni(1-x)CoxO4+δ (0.00 ≤ × ≤ 1.00), were synthesized and studied for their potential use as cathodes for solid-oxide fuel cells. An unusual structural trend has been noted across the series, which appears to correlate with the oxygen-hyperstoichiometry observed. Details of the structural variance by x-ray and neutron diffraction, as well as selected physical properties for this system will be presented.
We show that dramatically different in-plane crystallographic textures can be produced in body centered cubic (bcc) metal thin films deposited under different conditions. The orientation distribution of polycrystalline bcc thin films on amorphous substrates often has a strong (110) fiber texture, and an in-plane texture may develop when deposition takes place with an off-normal incidence flux of energetic ions or atoms. Three orientations in Nb films have been observed in which the energetic particle flux coincides with crystal channeling directions. In-plane orientations in Mo films have also been obtained in magnetron sputtering systems. The selected orientations are reviewed, and examples are given in which the in-plane orientation of Mo deposited in two similar magnetron sputtering systems differs by a 90° rotation. The origins of in-plane texture in rectangular magnetron sputtering systems are discussed.
We describe our efforts to control the grain boundary alignment in polycrystalline thin films of silicon by using a biaxially textured template layer of CaF2 for photovoltaic device applications. We have chosen CaF2 as a candidate material due to its close lattice match with silicon and its suitability as an ion beam assisted deposition (IBAD) material. We show that the CaF2 aligns biaxially at a thickness of ~10 nm and, with the addition of an epitaxial CaF2 layer, has an in-plane texture of ~15°. Deposition of a subsequent layer of Si aligns on the template layer with an in-plane texture of 10.8°. The additional improvement of in-plane texture is similar to the behavior observed in more fully characterized IBAD materials systems. A germanium buffer layer is used to assist in the epitaxial deposition of Si on CaF2 template layers and single crystal substrates. These experiments confirm that an IBAD template can be used to biaxially orient polycrystalline Si.