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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.
Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the ‘peas in the pod’ questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.
Background: Advances in surgical leads have been thought to potentially enable improved low-back pain relief using SCS. A recently introduced 32-contact surgical lead, which couples multiple independent current control and anatomically-based neural targeting stimulation algorithms, allows for patient-specific programming optimization. We present a real world study of this surgical lead. Methods: A multi-center, consecutive, observational study of a new 32-contact surgical lead was carried out, using the Precision Spectra SCS System (Boston Scientific) in 100 subjects out to 12 months post-implant. We examined procedural information, programming parameters, and clinical outcomes including pain reduction (NRS), activities of daily living, and change in pain medications. Results: Surgical lead placement distribution was between T7 and L2, with most at top of T9 (26%). A mean reduction of 5.1 points (SD 2.15, p<0.001) from 7.8 (baseline) to 2.6 in overall pain was observed. A subset of subjects reporting low-back pain only exhibited a mean decrease of 6.0 points (SD 2.12, p<0.001) from 8.3 (baseline) to 2.2. Of these, 83.1% of subjects showed ≥50% back pain reduction. Increases in activities of daily living and reduction in pain medication usage were also observed in majority of subjects. Conclusions: Subjects implanted with a 32-contact surgical lead using a neural targeting algorithm demonstrated significant low-back pain reduction.
Little is known about the extent to which aging trajectories of different body systems share common sources of variance. We here present a large twin study investigating the trajectories of change in five systems: cardiovascular, respiratory, skeletal, morphometric, and metabolic. Longitudinal clinical data were collected on 3,508 female twins in the TwinsUK registry (complete pairs:740 monozygotic (MZ), 986 dizygotic (DZ), mean age at entry 48.9 ± 10.4, range 18–75 years; mean follow-up 10.2 ± 2.8 years, range 4–17.8 years). Panel data on multiple age-related variables were used to estimate biological ages for each individual at each time point, in linear mixed effects models. A weighted average approach was used to combine variables within predefined body system groups. Aging trajectories for each system in each individual were then constructed using linear modeling. Multivariate structural equation modeling of these aging trajectories showed low genetic effects (heritability), ranging from 2% in metabolic aging to 22% in cardiovascular aging. However, we found a significant effect of shared environmental factors on the variations in aging trajectories in cardiovascular (54%), skeletal (34%), morphometric (53%), and metabolic systems (53%). The remainder was due to environmental factors unique to each individual plus error. Multivariate Cholesky decomposition showed that among aging trajectories for various body systems there were significant and substantial correlations between the unique environmental latent factors as well as shared environmental factors. However, there was no evidence for a single common factor for aging. This study, the first of its kind in aging, suggests that diverse organ systems share non-genetic sources of variance for aging trajectories. Confirmatory studies are needed using population-based twin cohorts and alternative methods of handling missing data.
Objectives: We describe a new evidence-based method for screening and evaluating emerging medical technologies. Washington State agencies, under legislative direction, have granted authority to its agency Medical Directors and policy leaders to make coverage decisions on medical technologies using a “dossier” process. The dossier process is employed when technology advocates or manufacturers request Washington State healthcare purchasers to pay for new and emerging technologies. This offers the advocate an opportunity to submit scientific evidence and information classically associated with a more formal health technology assessment.
Methods: The submitted information is independently reviewed and summarized for Washington State's public healthcare purchasers allowing a more standardized coverage decision for all public purchasers in Washington State.
Results: This process has allowed Washington State to make twelve evidence-based coverage decisions at a fraction of the cost of classic technology assessment. To date, of twelve reviews over 6 years, one health technology was approved for coverage, ten were not covered and one did not require a coverage decision.
Conclusions: This evidence-based dossier process has yielded high-value coverage decisions of new and emerging medical technologies for public healthcare purchasers in Washington State.
Sudden release of accreted ice in fuel systems could pose a serious challenge in aircraft operation. The resultant snowshower may reach the filter and fuel-oil heat exchanger, causing a restriction in fuel flow to the engine. It is fundamental to have an appreciation of the character and the interface shear strength of the accreted ice in aircraft fuel systems. This helps to recognise factors for the sudden release of the accreted ice and the intensity of the consequential snowshower. An experimental study was carried out to quantify the character and the interface shear strength of accreted ice on subcooled surfaces submerged in jet fuel. Ice was accreted on naked aluminium, painted aluminium and carbon fibre composite surfaces at various subcooled temperatures. The accreted ice was akin to fresh snow and exhibited soft and fluffy attributes. The character may be expressed quantitatively in terms of the porosity and was found to be c. 0·95. The ice weakly adhered to the substrate surfaces, and the interface shear strength was found to be c. 0·36Pa and c. 2·19Pa at the top surface and at the vertical surface of a specimen block, respectively. It was not possible to detect any variation in the porosity and the interface shear strength for different types of surface finishes and differences in water affnity in fuels due to the crude approach in the estimation of these parameters.
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.
TwinsUK is a nation-wide registry of volunteer twins in the United Kingdom, with about 12,000 registered twins (83% female, equal number of monozygotic and dizygotic twins, predominantly middle-aged and older). Over the last 20 years, questionnaire and blood/urine/tissue samples have been collected on over 7,000 subjects, as well as three comprehensive phenotyping assessments in the clinical facilities of the Department of Twin Research and Genetic Epidemiology, King's College London. The primary focus of study has been the genetic basis of healthy aging process and complex diseases, including cardiovascular, metabolic, musculoskeletal, and ophthalmologic disorders. Alongside the detailed clinical, biochemical, behavioral, and socio-economic characterization of the study population, the major strength of TwinsUK is availability of several ‘omics’ technologies for the participants. These include genome-wide scans of single nucleotide variants, next-generation sequencing, exome sequencing, epigenetic markers (MeDIP sequencing), gene expression arrays and RNA sequencing, telomere length measures, metabolomic profiles, and gut flora microbiomics. The scientific community now can freely access parts of the phenotype data from the ‘TwinsUK’, and interested researchers are encouraged to contact us via our Web site (www.twinsuk.ac.uk) for future collaborations.
Energy is essential for human development and energy systems are a crucial entry point for addressing the most pressing global challenges of the 21st century, including sustainable economic, and social development, poverty eradication, adequate food production and food security, health for all, climate protection, conservation of ecosystems, peace, and security. Yet, more than a decade into the 21st century, current energy systems do not meet these challenges.
In this context, two considerations are important. The first is the capacity and agility of the players within the energy system to seize opportunities in response to these challenges. The second is the response capacity of the energy system itself, as the investments are long-term and tend to follow standard financial patterns, mainly avoiding risks and price instabilities. This traditional approach does not embrace the transformation needed to respond properly to the economic, environmental, and social sustainability challenges of the 21st century.
A major transformation is required to address these challenges and to avoid potentially catastrophic consequences for human and planetary systems. The GEA identifies strategies that could help resolve the multiple challenges simultaneously and bring multiple benefits. Their successful implementation requires determined, sustained, and immediate action.
The industrial revolution catapulted humanity onto an explosive development path, whereby reliance on muscle power and traditional biomass was replaced mostly by fossil fuels. In 2005, approximately 78% of global energy was based on fossil energy sources that provided abundant and ever cheaper energy services to more than half the world's population.
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.
This paper proposes a new method for estimating Automatic Identification System (AIS) coverage empirically from received transmissions. The method is appropriate for stationary coverage assets, as distinct from aircraft and satellites. The key idea behind the method is to interpolate probabilistically between AIS reports in order to reconstruct where the missed transmissions might have occurred. These hypothetical missed transmissions then supplement the received ones in a coverage estimate based on a Bayesian treatment of a binomial model of reception. The final estimate of the coverage is implemented over a spatial grid. The method is demonstrated on simulated AIS data and was found to have lower mean squared error than a previously published method. Assumptions and potential weaknesses of the new method are discussed.
We present a method for addressing probabilistic queries about the location of a vessel in the time interval between two position reports, such as from the Automatic Identification System (AIS). The heart of the method is the random generation of physically feasible paths connecting the two reports. The method empowers operators to answer probabilistic questions about any characteristic of the unknown true path. For illustrative purposes, we demonstrate the use of the method to identify which of several vessels is the most likely perpetrator, in a fictitious scenario in which illegal dumping of waste matter has taken place.
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.
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.