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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.
Although many mental health care systems provide care interventions that are not related to direct health care, little is known about the interfaces between the latter and core health care. ‘Core health care’ refers to services whose explicit aim is direct clinical treatment which is usually provided by health professionals, i.e., physicians, nurses, psychologists. ‘Other care’ is typically provided by other staff and includes accommodation, training, promotion of independence, employment support and social skills. In such a definition, ‘other care’ does not necessarily mean being funded or governed differently. The aims of the study were: (1) using a standard classification system (Description and Evaluation of Services and Directories in Europe for Long Term Care, DESDE-LTC) to identify ‘core health’ and ‘other care’ services provided to adults with mental health problems; and (2) to investigate the balance of care by analysing the types and characteristics of core health and other care services.
The study was conducted in eight selected local areas in eight European countries with different mental health systems. All publicly funded mental health services, regardless of the funding agency, for people over 18 years old were identified and coded. The availability, capacity and the workforce of the local mental health services were described using their functional main activity or ‘Main Types of Care’ (MTC) as the standard for international comparison, following the DESDE-LTC system.
In these European study areas, 822 MTCs were identified as providing core health care and 448 provided other types of care. Even though one-third of mental health services in the selected study areas provided interventions that were coded as ‘other care’, significant variation was found in the typology and characteristics of these services across the eight study areas.
The functional distinction between core health and other care overcomes the traditional division between ‘health’ and ‘social’ sectors based on governance and funding. The overall balance between core health and other care services varied significantly across the European sites. Mental health systems cannot be understood or planned without taking into account the availability and capacity of all services specifically available for this target population, including those outside the health sector.
Background: NEDA is a composite measure that may ultimately influence clinical decisions concerning switches of disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS) patients. Cohort studies from MS clinics suggest NEDA is not sustained over time in most patients despite DMT but may be limited by referral bias. We investigated NEDA in a population-based RRMS cohort. Methods: We identified all incident cases of RRMS in Olmsted County from 01/01/2000-12/31/2011. Retrospective chart review was conducted to determine persistence of NEDA -following RRMS diagnosis. NEDA failure was defined as new MRI activity, relapse, or expanded disability status scale (EDSS) -worsening. Results: There were 93 incident cases of RRMS with 82 individuals having sufficient follow-up to determine persistence of NEDA. Prior to NEDA failure 44 were not on DMT, 37 were on first-tier, injectable DMT, and 1 received mitoxantrone. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years. Disability measured by EDSS was no different at 10 years in patients maintaining NEDA versus those that failed NEDA at one year (p=0.3). Conclusions: Maintenance of NEDA beyond 2 years is infrequent among a population-based cohort of newly diagnosed RRMS patients and similar to prior clinic-based cohorts.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.
Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.
Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory Emax model we developed previously.
The inhibitory Emax model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), −5.67 (dorsal raphe nucleus)].
This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
The spectral and temporal behavior of exoplanet host stars is a critical input to models of the chemistry and evolution of planetary atmospheres. High-energy photons (X-ray to NUV) from these stars regulate the atmospheric temperature profiles and photochemistry on orbiting planets, influencing the production of potential “biomarker” gases. We report first results from the MUSCLES Treasury Survey, a study of time-resolved UV and X-ray spectroscopy of nearby M and K dwarf exoplanet host stars. This program uses contemporaneous Hubble Space Telescope and Chandra (or XMM) observations to characterize the time variability of the energetic radiation field incident on the habitable zones planetary systems at d ≲ 20 pc. We find that all exoplanet host stars observed to date exhibit significant levels of chromospheric and transition region UV emission. M dwarf exoplanet host stars display 30–7000% UV emission line amplitude variations on timescales of minutes-to-hours. The relative flare/quiescent UV flux amplitudes on weakly active planet-hosting M dwarfs are comparable to active flare stars (e.g., AD Leo), despite their weak optical activity indices (e.g., Ca II H and K equivalent widths). We also detect similar UV flare behavior on a subset of our K dwarf exoplanet host stars. We conclude that strong flares and stochastic variability are common, even on “optically inactive” M dwarfs hosting planetary systems. These results argue that the traditional assumption of weak UV fields and low flare rates on older low-mass stars needs to be revised.
We present an analysis of a sample of flares on “quiescent” (i.e. non-flare) M and K stars using temporally resolved UV spectroscopy from the growing body of MUSCLES Treasury Survey data. Specifically, our analysis quantified the response of the far-UV C II, Si III, Si IV, and N V emission lines and the far-UV continuum during the flares. Using these tracers, we examined one representative event on GJ 832. In concordance with flares recorded on the Sun and AD Leo, the MUSCLES flares are well fit by a power law relationship of similar slope in frequency versus energy. Flares can strip atmospheric mass from orbiting planets, adversely affecting their long-term habitability. To gauge the amplitude of this effect, we computed an energy-balance upper-limit on the amount of atmosphere a large flare might remove from an orbiting Earth due purely to elevated EUV flux and found this limit to be modest relative to Earth's atmospheric mass.
We report the implementation of an automated reel-to-reel fluidic self-assembly system based on surface-tension driven self-assembly for macroelectronics application. The reported system incorporates precisely controlled and automated agitation, web moving, component recycling, and dispensing system. The system enables continuous parallel assembly of semiconductor chips at a high rate (15,000 chips per hour using 2.5 cm wide web) and assembly yield (>99%) under optimal condition. In principle, scaling to any throughput should be possible considering the parallel nature of self-assembly. The process overcomes the limitations on area and throughput of prior methods. It provides a new platform for macroelectronics to enable the integration of microscopic high performance inorganic semiconductors on flexible substrates with any desired location, pitch, and integration density. As an example we demonstrate the fabrication of a solid state area lighting module.
A single-grained Pb(Zr,Ti)O3 (PZT) was successfully grown for the gate dielectric of polycrystalline-silicon (poly-Si) thin-film transistor (TFT). The total structure was MoW/PZT/HfO2/poly-Si/glass. The giant single-grained PZT was obtained by controlling the artificial nucleation formed by Pt dots in a desirable location and enlarging the nucleated seed until it covers the poly-Si channel. The single-grained diameter size was 40 μm with a (100) dominated texture. The poly-Si memory device with single-grained PZT showed an excellent ferroelectric, electrical and reliability properties comparing with poly-Si memory device with poly-grained PZT. Moreover, eliminating the grain boundary in PZT film showed the fatigue and retention characteristics with only 1.1 % after 1013 cycles and 22 % after 1 month, respectively.
We propose a framework for indexing of grain and subgrain structures in electron backscatter diffraction patterns of polycrystalline materials. We discretize the domain of a dynamical forward model onto a dense grid of orientations, producing a dictionary of patterns. For each measured pattern, we identify the most similar patterns in the dictionary, and identify boundaries, detect anomalies, and index crystal orientations. The statistical distribution of these closest matches is used in an unsupervised binary decision tree (DT) classifier to identify grain boundaries and anomalous regions. The DT classifies a pattern as an anomaly if it has an abnormally low similarity to any pattern in the dictionary. It classifies a pixel as being near a grain boundary if the highly ranked patterns in the dictionary differ significantly over the pixel’s neighborhood. Indexing is accomplished by computing the mean orientation of the closest matches to each pattern. The mean orientation is estimated using a maximum likelihood approach that models the orientation distribution as a mixture of Von Mises–Fisher distributions over the quaternionic three sphere. The proposed dictionary matching approach permits segmentation, anomaly detection, and indexing to be performed in a unified manner with the additional benefit of uncertainty quantification.
The detection of single molecular binding events has been a recent trend in sensor research introducing various sensor designs where the active sensing elements are nanoscopic in size. Currently, diffusion-only-transport is often used and it becomes increasingly unlikely for an analyte molecule to “find” and interact with sensing structures where the active area is shrunk in size, trading an increased sensitivity with a long response time. This report introduces electrodynamic nanolens based analyte concentration concepts to transport airborne analytes to nanoscopic sensing points to improve the response time of existing gas sensor designs. In all cases we find that the collection rate is several orders of magnitudes higher than in the case where the collection is driven by diffusion.
Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs.
This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer.
Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis.
Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay.
Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.
Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002–2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32–4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17–4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01–3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35–9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10–6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06–7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.
InGaN/GaN multi-quantum well (MQW) laser diodes (LDs) were grown on c-plane sapphire substrates using a multi-wafer MOCVD system. The threshold current for pulsed lasing was 1.6 A for a gain-guided laser diode with a stripe of 10 × 800 μm2. The threshold current density was 20.3 kA cm−2 and the threshold voltage was 16.5 V. The optical power ratio of transverse electric mode to transverse magnetic mode was found to be greater than 50. The characteristic temperature measured from the plot of threshold current versus measurement temperature was between 130 and 150K.
Breast cancer metastasis to bone continues to be a major clinical problem, and patient-to-patient variability in rates of disease progression and metastasis complicate treatment even further. This may be due to differences in the cancer cells, the osteoclasts, or the pre-metastatic niche, but all of these contribute to proteolytic remodeling necessary for osteolytic lesion establishment, primarily through secretion of cathepsin K, the most powerful human collagenase. There is debate about the relative contributions of breast cancer cells and osteoclasts and synergism between the two in altering the biochemical and biomechanical properties of the colonized bone, as these are difficult to parse with animal models. To quantify the relative contributions of breast cancer cells and osteoclasts in bone resorption, we have been developing engineered bone microenvironment tissue surrogates by adapting a poly(ester urethane) urea system embedded with microbone particles. Here, we report their use with MDA-MB-231 breast cancer cells and RAW264.7 derived osteoclasts, to provide temporal, multiscale reporters of bone resorption that can be measured non-destructively: 1) collagen degradation measured by C-terminal collagen fragment release, 2) mineral dissolution by measuring calcium released with the calcium arsenazo assay, and also show their beneficial effects in upregulating cathepsin K expression compared to tissue culture polystyrene controls. These more natural derived bone surrogates may be useful tools in mimicking bone metastatic niche and determining differences between proteolytic activity of different patients’ tumor and bone resident cells in a controlled manner.
The use of machine vision to guide robotic spacecraft is being considered for a wide range of missions, such as planetary approach and landing, asteroid and small body sampling operations and in-orbit rendezvous and docking. Numerical simulation plays an essential role in the development and testing of such systems, which in the context of vision-guidance means that realistic sequences of navigation images are required, together with knowledge of the ground-truth camera motion. Computer generated imagery (CGI) offers a variety of benefits over real images, such as availability, cost, flexibility and knowledge of the ground truth camera motion to high precision. However, standard CGI methods developed for terrestrial applications lack the realism, fidelity and performance required for engineering simulations.
In this paper, we present the results of our ongoing work to develop a suitable CGI-based test environment for spacecraft vision guidance systems. We focus on the various issues involved with image simulation, including the selection of standard CGI techniques and the adaptations required for use in space applications. We also describe our approach to integration with high-fidelity end-to-end mission simulators, and summarise a variety of European Space Agency research and development projects that used our test environment.
Donor-acceptor mixed-stack charge-transfer (CT) compounds can be regarded as a model system for charge carrier separation in molecular-scale donor-acceptor heterojunctions. Here we investigated fundamental photocarrier generation characteristics in single crystals of a donoracceptor mixed-stack system, phenothiazine-tetracyanoquinodimethane (PTZ-TCNQ). The laser beam-induced current (LBIC) measurement on the crystals allowed the discrimination between the exciton and the photocarrier diffusion on the basis of the observed spatial decay profiles. We found that the photocarriers are directly generated by higher-lying CT band excitation and exhibit extremely long diffusion length reaching more than 10 μm. We discuss the origin of the efficient photocarrier generation in terms of the geminate electron-hole pair formation.
The Burst Observer and Optical Transient Exploring System (BOOTES), is a global robotic
observatory network, which started in 1998 with Spanish leadership devoted to study
optical emissions from gamma ray bursts (GRBs) that occur in the Universe. We present shot
history and current status of BOOTES network. The Network philosophy, science and some
details of 117 GRBs followed-up are discussed.
In this paper we study the density of states in n-type N,N’-ditridecylperylene-3,4,9,10-tetracarboxylic diimide organic semiconductor using two different methods. The first one is based on the temperature dependence of the channel conductance in field-effect transistors. The second one is based on the subgap optical absorption coefficient measured using the Photothermal Deflection Spectroscopy technique. Both techniques allow estimating the distribution of localized states in the band gap of the semiconductor.