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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.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
The Icelandic crust is characterized by low δ18O values that originate from pervasive high-temperature hydrothermal alteration by 18O-depleted meteoric waters. Igneous rocks in Iceland with δ18O values significantly higher than unaltered oceanic crust (~5.7‰) are therefore rare. Here we report on rhyolitic intra-caldera samples from a cluster of Neogene central volcanoes in Borgarfjörður Eystri, Northeast Iceland, that show whole-rock δ18O values between +2.9 and +17.6‰ (n = 6), placing them among the highest δ18O values thus far recorded for Iceland. Extra-caldera rhyolite samples from the region, in turn, show δ18O whole-rock values between +3.7 and +7.8‰ (n = 6), consistent with the range of previously reported Icelandic rhyolites. Feldspar in the intra-caldera samples (n = 4) show δ18O values between +4.9 and +18.7‰, whereas pyroxene (n = 4) shows overall low δ18O values of +4.0 to +4.2‰, consistent with regional rhyolite values. In combination with the evidence from mineralogy and rock H2O contents, the high whole-rock δ18O values of the intra-caldera rhyolites appear to be the result of pervasive isotopic exchange during subsolidus hydrothermal alteration with 18O-enriched water. This alteration conceivably occurred in a near-surface hot spring environment at the distal end of an intra-caldera hydrothermal system, and was probably fed by waters that had already undergone significant isotope exchange with the country rock. Alternatively, 18O-enriched alteration fluids may have been produced during evaporation and boiling of standing water in former caldera lakes, which then interacted with the intra-caldera rock suites. Irrespective of the exact exchange processes involved, a previously unrecognized and highly localized δ18O-enriched rock composition exists on Iceland and thus probably within the Icelandic crust too.
To determine the impact of recurrent Clostridium difficile infection (RCDI) on patient behaviors following illness.
Using a computer algorithm, we searched the electronic medical records of 7 Chicago-area hospitals to identify patients with RCDI (2 episodes of CDI within 15 to 56 days of each other). RCDI was validated by medical record review. Patients were asked to complete a telephone survey. The survey included questions regarding general health, social isolation, symptom severity, emotional distress, and prevention behaviors.
In total, 119 patients completed the survey (32%). On average, respondents were 57.4 years old (standard deviation, 16.8); 57% were white, and ~50% reported hospitalization for CDI. At the time of their most recent illness, patients rated their diarrhea as high severity (58.5%) and their exhaustion as extreme (30.7%). Respondents indicated that they were very worried about getting sick again (41.5%) and about infecting others (31%). Almost 50% said that they have washed their hands more frequently (47%) and have increased their use of soap and water (45%) since their illness. Some of these patients (22%–32%) reported eating out less, avoiding certain medications and public areas, and increasing probiotic use. Most behavioral changes were unrelated to disease severity.
Having had RCDI appears to increase prevention-related behaviors in some patients. While some behaviors are appropriate (eg, handwashing), others are not supported by evidence of decreased risk and may negatively impact patient quality of life. Providers should discuss appropriate prevention behaviors with their patients and should clarify that other behaviors (eg, eating out less) will not affect their risk of future illness.
Academic health systems and their investigators are challenged to systematically assure clinical research regulatory compliance. This challenge is heightened in the emerging era of centralized single Institutional Review Boards for multicenter studies, which rely on monitoring programs at each participating site.
To describe the development, implementation, and outcome measurement of an institution-wide paired training curriculum and internal monitoring program for clinical research regulatory compliance.
Standard operating procedures (SOPs) were developed to facilitate investigator and research professional adherence to institutional policies, federal guidelines, and international standards. An SOP training curriculum was developed and implemented institution-wide. An internal monitoring program was launched, utilizing risk-based monitoring plans of pre-specified frequency and intensity, assessed upon Institutional Review Boards approval of each prospective study. Monitoring plans were executed according to an additional SOP on internal monitoring, with monitoring findings captured in a REDCap database.
We observed few major violations across 3 key domains of clinical research conduct and demonstrated a meaningful decrease in the rates of nonmajor violations in each, over the course of 2 years.
The paired training curriculum and monitoring program is a successful institution-wide clinical research regulatory compliance model that will continue to be refined.
Multijunction solar cells have proven to be capable of extremely high efficiencies by combining multiple semiconductor materials with bandgaps tuned to the solar spectrum. Reaching the optimum set of semiconductors often requires combining high-quality materials with different lattice constants into a single device, a challenge particularly suited for metamorphic epitaxy. In this article, we describe different approaches to metamorphic multijunction solar cells, including traditional upright metamorphic, state-of-the-art inverted metamorphic, and forward-looking multijunction designs on silicon. We also describe the underlying materials science of graded buffers that enables metamorphic subcells with low dislocation densities. Following nearly two decades of research, recent efforts have demonstrated high-quality lattice-mismatched multijunction solar cells with very little performance loss related to the mismatch, enabling solar-to-electric conversion efficiencies over 45%.
A mechanistic model (COWPOLL) was used to estimate enteric methane (CH4) emissions from beef production systems in Chile. The results expressed as a proportion of gross energy intake (GEI) were compared with enteric fermentation data reported in the last Chilean greenhouse gases inventory, which utilized an earlier the Intergovernmental Panel on Climate Change Tier 2 approach. The simulation analysis was based on information from feedstuffs, dry matter intake (DMI), body weight (BW) and average daily gain (ADG) of steers raised and finished at two research facilities located in Central and Southern Chile, as well as three simulated scenarios for grass-based finishing systems in Southern Chile. Data for feedlot production systems in the central region were assessed by considering steers fed a forage : concentrate ratio of 23 : 77 using maize silage and wheat straw as roughage sources during the stages of backgrounding and fattening. Average DMI were 7·3±0·62 and 9·2±0·55 kg/day per steer for backgrounding and fattening, respectively, whereas ADG were 1·1±0·22 and 1·3±0·37 kg/day for backgrounding and fattening. For the Southern Chilean fattening production systems, the forage : concentrate ratio was 56 : 44 with ryegrass pasture as the sole forage source. In this case, average DMI was 9·97±0·51 and ADG was 1·1±0·24 kg/day per steer. Two of the grass-based scenarios used the same initial BW information as that used for the Central and Southern Chilean systems, but feedlot diets were replaced by ryegrass pasture. The third grass-based scenario used an initial BW of 390 kg. In all the grass-based scenarios an ADG of 0·90 kg/day, with maximum DMI estimated as a proportion of BW (0·01 of NDF, kg/kg BW), was assumed. The results of the simulation analysis showed that emission factors (Ym; fraction of GEI) ranged from 0·062 to 0·079 of GEI. Smaller values were associated with finishing systems that included a lower proportion of forage in the diet due to higher propionate production, which serves as a sink for hydrogen in the rumen. Cattle finished in feedlot systems had an average of 0·062 of GEI lost as CH4, whereas grass-based cattle had losses of 0·079 of GEI. Enteric CH4 emissions for the systems using grass-based and concentrate diets were 261 and 159 g/kg weight gain, respectively. The Chilean CH4 inventory employs a fixed Ym of 0·060 to estimate enteric fermentation for all cattle. This value is lower than the average Ym obtained in the current simulation analysis (0·071 of GEI), which results in underestimation of enteric CH4 emissions from beef cattle. However, these results need to be checked against field measurements of CH4 emissions. Implementation of mechanistic models in the preparation of national greenhouse gas inventories is feasible if appropriate information is provided, allowing dietary characteristics and regional particularities to be taken into consideration.
The objective of the current study was to evaluate the utilization of calcium (Ca) and phosphorus (P) in growing sheep consuming increasing amounts of dicalcium phosphate. Eighteen growing sheep, aged 8 months, were fed a basal diet supplemented with 0, 12·5 and 25 g of dicalcium phosphate/day. During the experiment, animals were injected intravenously with 7·4 MBq of 45Ca and 32P and samples of plasma, faeces and urine were subsequently taken daily for 1 week after injection. Rumen fluid was sampled on days 4–7 after injection. Specific radioactivity in plasma and in faeces were used to determine true absorption of Ca and P, whereas plasmatic and ruminal specific radio-activities were used to determine endogenous P flow into the rumen and turnover time of rumen P. Increasing dicalcium phosphate intake led to linear increases in faecal excretion of endogenous Ca and P (P<0·05), suggesting that surpluses of ingested Ca and P were voided through secretion to the gut. True absorption coefficients for 0, 12·5 and 25 g of dicalcium phosphate ingested daily were 0·54, 0·41 and 0·38 for Ca, and 0·66, 0·62 and 0·64 for P, respectively. Flows of endogenous P into the rumen increased linearly and ruminal turnover time of P decreased linearly (P<0·01) as P intake was increased. Concentrations of Ca and P in bone were not affected by the increased amounts of these minerals ingested (P<0·05). In conclusion, increasing ingestion of dicalcium phosphate increases faecal excretion of Ca and P, thus decreasing the efficiency of utilization of both minerals. Moreover, increasing levels of dietary P increased endogenous P excretion, contributing to the amount of P disposed of in the environment.