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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.
Modelling a normal–superconducting interface, we consider a semi-infinite wire whose edge is adjacent to a normal magnetic metal, assuming asymptotic convergence, away from the boundary, to the purely superconducting state. We obtain that the maximal current which can be carried by the interface diminishes in the small normal conductivity limit.
In recent years, a number of experimental X-ray diffraction techniques have been developed by which a topographical display of the microscopical defects in a crystal can be obtained. This brief review of the most useful of these techniques is intended to summarize the elements of the various methods and to compare their respective features and limitations. Contrary to microradiographic methods, in which image contrast is due entirely to variations in X-ray absorption from point to point in the specimen, X-ray diffraction topography is concerned with point-topoint variations in the directions or the intensities of X-rays that have been diffracted by crystals. From these variations the defect structure of the crystal may be examined. Methods that mainly measure local variations in the direction of the diffracted beam are useful for the detection of gross misorientations such as subgrains or grains (methods of Gui nier and Tennevin, Schulz, Weissmann). Intensity mapping methods are chiefly concerned with individual defects such as dislocations, stacking faults, etc. In both groups there are experimental arrangements with both Laue-case (transmission) and Bragg-case (back reflection) geometry.
Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.
Introduction: The ECG diagnosis of acute coronary occlusion (ACO) in the setting of ventricular paced rhythm (VPR) is purported to be impossible. However, VPR has a similar ECG morphology to LBBB. The validated Smith-modified Sgarbossa criteria (MSC) have high sensitivity (Sens) and specificity (Spec) for ACO in LBBB. MSC consist of 1 of the following in 1 lead: concordant ST Elevation (STE) 1 mm, concordant ST depression 1 mm in V1-V3, or ST/S ratio <−0.25 (in leads with 1 mm STE). We hypothesized that the MSC will have higher Sens for diagnosis of ACO in VPR when compared to the original Sgarbossa criteria. We report preliminary findings of the Paced Electrocardiogram Requiring Fast Emergency Coronary Therapy (PERFECT) study Methods: The PERFECT study is a retrospective, multicenter, international investigation of ED patients from 1/2008 - 12/2016 with VPR on the ECG and symptoms suggestive of acute coronary syndrome (e.g. chest pain or shortness of breath). Data from four sites are presented. Acute myocardial infarction (AMI) was defined by the Third Universal Definition of AMI. A blinded cardiologist adjudicated ACO, defined as thrombolysis in myocardial infarction score 0 or 1 on coronary angiography; a pre-defined subgroup of ACO patients with peak cardiac troponin (cTn) >100 times the 99% upper reference limit (URL) of the cTn assay was also analyzed. Another blinded physician measured all ECGs. Statistics were by Mann Whitney U, Chi-square, and McNemars test. Results: The ACO and No-AMI groups consisted of 15 and 79 encounters, respectively. For the ACO and No-AMI groups, median age was 78 [IQR 72-82] vs. 70 [61-75] and 13 (86%) vs. 48 (61%) patients were male. The median peak cTn ratio (cTn/URL) was 260 [33-663] and 0.5 [0-1.3] for ACO vs. no-AMI. The Sens and Spec for the MSC and the original Sgarbossa criteria were 67% (95%CI 39-87) vs. 46% (22-72; p=0.25) and 99% (92-100) vs. 99% (92-100; p=0.5). In pre-defined subgroup analysis of ACO patients with peak cTn >100 times the URL (n=10), the Sens was 90% (54-100) for the MSC vs. 60% (27- 86) for original Sgarbossa criteria (p=0.25). Conclusion: ACO in VPR is an uncommon condition. The MSC showed good Sens for diagnosis of ACO in the presence of VPR, especially among patients with high peak cTn, and Spec was excellent. These methods and results are consistent with studies that have used the MSC to diagnose ACO in LBBB.
Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse.
Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions.
Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls.
The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.
Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions.
Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13–20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted.
For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA.
Childhood abuse is associated with widespread structural abnormalities in OFC–insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.
A technique proposed by Hooke and Iverson (1995) to identify deformed subglacial sediments is reviewed and tested, based on two main objectives. First, an investigation of whether the fractal dimension can distinguish between non-deformed and deformed facies; for which we compare supraglacial and subglacial facies explicitly. Second, an evaluation of whether the fractal dimension can be used as a diagnostic criteria to discriminate between different styles and degrees of basal deformation. This is tested using a range of sediments from the deformation continuum suggested by Hart and Boulton (1991b). Sixteen subglacial samples were selected from Quaternary sites in England and three supraglacial samples from the modern Haut Glacier d’Arolla, Switzerland. The mean fractal dimension for the subglacial diamicton matrix facies was 2.92, similar to findings of 2.90 by Hooke and Iverson (1995) for their basal tills. The supraglacial facies displayed a mean fractal dimension of 2.83, which is unusually high for facies which are assumed to be undeformed. A Mann—Whitney U test showed that fractal dimensions of supraglacial and subglacial diamicton matrix facies were not significantly different. No significant difference was found between the fractal dimensions of the different tectonic facies within the subglacial group. It may be impossible to separate the subglacial and supraglacial facies because of complex debris paths within the glacier. Grain fracture or parent lithology may affect the particle-size distribution of subglacial facies.
Different types of fast ice flow (both spatial and temporal) in valley glaciers (surging glaciers, tidewater glaciers and deforming-bed glaciers) and ice sheets (ice streams and deforming-bed ice-sheet flow) are discussed briefly. Although there are unlikely to be any specific individual landforms associated with fast ice flow, there may be landform assemblages.
At valley glacier scale, it is suggested that there are two landform assemblages: (1) an ice-thrust type, dominated by bulldozed push moraines and hummocky moraines (associated with glaciers with a high supraglacial sediment supply, a coarse-grained substrate and a coarse-grained proglacial sediment wedge); and (2) a bed-flow type dominated by “squeeze” push moraines, flutes and drumlins (associated with glaciers with a low supra- glacial sediment supply and fine-grained substrate). The ice-thrust type alone is only associated with discontinuous fast flow (on both rigid and deforming beds); whilst the bed-flow type is associated with both continuous and discontinuous fast flow.
It is suggested that these two landform assemblages may also be indicative of fast ice flow at ice-sheet scale, in particular the bed-flow style. If that is the case, then discontinuous fast ice flow may be indicated by the ice-thrust landform assemblage and the bed-flow style where drumlins are present.
It is also suggested that specific evidence for ice streams includes the distinctive land-form assemblages within valley or fan-like locations, and a predictable pattern of velocity reflected by drumlin elongation ratios.
The upper 20—30 m of ice-rich permafrost at three sites overridden by the northwest margin of the Laurentide ice sheet in the Tuktoyaktuk Coastlands, western Arctic Canada, comprise massive ice beneath ice-rich diamicton or sandy silt. The diamicton and silt contain (1) truncated ice blocks up to 15 m long, (2) sand lenses and layers, (3) ice veins dipping at 20—30°, (4) ice lenses adjacent and parallel to sedimentary contacts, and (5) ice wedges. The massive ice is interpreted as intrasedimental or buried basal glacier ice, and the diamicton and silt as glacitectonite that has never thawed. Deformation of frozen ground was mainly ductile in character. Deformation was accompanied by sub-marginal erosion of permafrost, which formed an angular unconformity along the top of the massive ice and supplied ice clasts and sand bodies to the overlying glacitectonite. After deformation and erosion ceased, postglacial segregated ice and ice- wedge ice developed within the deformed permafrost.
This paper introduces a new way to investigate in situ processes, the wireless multi-sensor probe, as part of an environmental sensor network. Instruments are housed within a ‘probe’ which can move freely and so behave like a clast. These were deployed in the ice and till at Briksdalsbreen, Norway. The sensors measure temperature, resistivity, case stress, tilt angle and water pressure and send their data to a base station on the glacier surface via radio links. These data are then forwarded by radio to a reference station with mains power 2.5 km away, from where they are sent to a web server in the UK. The system deployed during 2004/05 was very successful and a total of 859 probe days worth of data from the ice and till were collected, along with GPS, weather and diagnostic data about the system.
A legionellosis outbreak at an industrial site was investigated to identify and control the source. Cases were identified from disease notifications, workplace illness records, and from clinicians. Cases were interviewed for symptoms and risk factors and tested for legionellosis. Implicated environmental sources were sampled and tested for legionella. We identified six cases with Legionnaires’ disease and seven with Pontiac fever; all had been exposed to aerosols from the cooling towers on the site. Nine cases had evidence of infection with either Legionella pneumophila serogroup (sg) 1 or Legionella longbeachae sg1; these organisms were also isolated from the cooling towers. There was 100% DNA sequence homology between cooling tower and clinical isolates of L. pneumophila sg1 using sequence-based typing analysis; no clinical L. longbeachae isolates were available to compare with environmental isolates. Routine monitoring of the towers prior to the outbreak failed to detect any legionella. Data from this outbreak indicate that L. pneumophila sg1 transmission occurred from the cooling towers; in addition, L. longbeachae transmission was suggested but remains unproven. L. longbeachae detection in cooling towers has not been previously reported in association with legionellosis outbreaks. Waterborne transmission should not be discounted in investigations for the source of L. longbeachae infection.
In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; P<0.01; day 11: calm 1.83; nervous 1.57; P<0.05). Ovulation rate on day 11 in nervous ewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; P<0.01). Reproductive loss between days 30 and 74 represented 7.3% of the overall loss. Temperament did not affect concentrations of progesterone, but nervous ewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect differences in energy utilisation.