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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.
X-ray computed tomography (CT) measurements of live sheep have been used to predict carcass composition very accurately (Macfarlane et al., 2006). The utilisation of spiral CT scans (SCTS) for quantifying muscle volumes and weights, using automatic image analysis procedures has also been shown to be very accurate in sheep (Navajas et al., 2006). Although the limiting size of the CT gantry prevents CT scanning of live beef cattle, beef primal joints are small enough to be scanned. Hence, SCTS could be used to quantify beef carcass composition, and provide valuable information for breeding programmes including composition faster than by anatomical dissection. The objective of this study was to develop a CT image analysis procedure to assess fat, muscle and bone weights of beef carcasses and to evaluate its accuracy.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Clinical disaster medicine requires providers working collaboratively to care for multiple patients, yet many clinicians lack competency-based training. A 5-hour emergency preparedness training (EPT) curriculum was created using didactics, small group discussion, and scenario-based learning. The goal was to evaluate the effect of a short course on improving clinical-provider knowledge, confidence and skill.
Participants were enrolled in a medical university between 2011 and 2014. The course consisted of didactic lectures, small group exercises, and live mass-casualty training scenarios. Core competencies and performance objectives were developed by a task force and assessed via facilitator observation, pre- and posttesting, and a course evaluation.
A total of 708 participants were trained, including 49.9% physicians, 31.9% medical students, 7.2% nurses, and 11% allied health personnel. The average percentage of correct answers increased from 39% to 60% (P<0.01). Following didactics, trainees met 73% and 96% of small group performance objectives. Trainees also met 68.5% and 61.1% of the mass-casualty performance objectives. Average trainee self-assessment of disaster-preparedness skill improved from 36 to 73 points out of 100.
A brief, intensive EPT course can improve the disaster knowledge and comfort level of a diverse group of clinical providers as well as foster disaster-performance skills. (Disaster Med Public Health Preparedness. 2018;12:121–126)
We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Methods Eighty seven people with 1-3 brain metastases were enrolled on this Phase II trial of WBRT (30Gy/10)+simultaneous FSRT, (60Gy/10). Results Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to<27) ranged from 26-38% for KPS, 32-59% for FACT-Br and 0-16%for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (<6months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. Conclusions The effects on function and quality of life of this integrated treatment of WBRT+simultaneous FSRT were similar to other published series combining WBRT+SRS.
Data on the depth distribution of the major atmospheric gases and the abundance of gaseous 12CO2, 13CO2, and 14CO2 in the subsoil unsaturated zone have been obtained from several sites in the western Great Plains of the United States. Sample profiles range from land surface to depths of 50m. Although each site must be considered on an individual basis, several general statements can be made regarding the profiles. 1) Diffusion of these gaseous molecules through the unsaturated zone is an important transport mechanism. 2) As predicted by diffusion theory, depth profiles of the various isotopic species of CO2 differ substantially from one another, depending on individual sources and sinks such as root respiration and oxidation of organic carbon at depth. 3) In general, post-bomb (> 100% modern) 14C activities are not observed in the deep unsaturated zone, in contrast to diffusion model predictions. 4) In spite of generally decreasing 14C activities with depth, absolute partial pressures of 14CO2 in the subsoil unsaturated zone are 1–2 orders of magnitude higher than the partial pressure of 14CO2 in the atmosphere.
Soil gas samples were obtained from the unsaturated zone at eight sites in the Great Plains. Three of these sites were sampled extensively for gas composition and carbon isotopes. Sampling equipment consisted of a nest of gas probes vertically spaced by roughly 3m at most sites, generally approaching the water table. Water wells, 10cm in diameter, were screened in the topmost layer groundwater. Inverted cattle tanks were used to collect CO2 samples from the soil surface. The major gas components were analyzed with emphasis on CO2, δ 13C, and 14C measurements. The same components were studied in groundwater samples. Higher than atmospheric CO2 concentrations were found in all soil samples. Root respiration and oxidation of organic matter were sources for the additional CO2. When lignite was present in the unsaturated zone, gaseous oxygen reacted almost completely, and CO2 levels rose to 19%. Near the surface, annual cycles in total CO2, δ 13C, and 14C were observed. 14C activities were close to present post-bomb levels at the surface and generally declined with depth. At some sites, oxidation of lignite caused decline of 14C levels to 1 or 2% of their surface value at 8m depth. Without lignite, the 14C activity remained above 50% at all depths. Concentrations of total carbon and its isotopes in ground water remained very stable throughout the study. This implies that geochemical processes in the aquifer vary on time scales longer than the seasonal effects observed in the near-surface unsaturated zone.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Adverse uterine environments caused by maternal stress (such as bacterial endotoxin) can alter programming of the fetal hypothalamic–pituitary–adrenal axis (HPAA) rendering offspring susceptible to various adulthood diseases. Thus, protection against this type of stress may be critical for ensuring offspring health. The present study was designed to determine if maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to protect against stress-induced fetal programming. Briefly, 53 ewes were fed a diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of gestation (gd100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin, or saline as the control. The offspring’s cortisol response to weaning stress was assessed 50 days postpartum by measuring serum cortisol concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 μg/kg) and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post challenge. Interestingly, female offspring born to FM+LPS mothers had a greater cortisol response to weaning and endotoxin challenge compared with the other treatments, while female offspring born to SM+LPS mothers had a faster cortisol response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a greater cortisol response to the ACTH challenge than the other treatments. Overall, FM supplementation during gestation combined with LPS challenge alters HPAA responsiveness of the offspring into adulthood.
Biogenic nitrogen (N2) and nitrous oxide (N2O) accumulations were measured in groundwater, streams and the vadose zone of small agricultural watersheds in the Mid-Atlantic USA. In general, N2 and N2O in excess of atmospheric equilibrium were found in groundwater virtually everywhere that was sampled. Excess N2 in groundwater ranged from undetectable to 616 μmol N2-N/l, the latter representing c. 50% of background N2. The N2O-N concentrations varied from undetectable to 75 μm, and usually greatly exceeded values at atmospheric equilibrium (25–30 nM); however, N2O was generally 1–10% of excess N2. Intermediate levels of deficit and excess N2 in flowing streams (−65 to +250 μmol N2-N/L) resulting from both abiotic and biotic processes were also measured. In vadose zone gases, multiple N2/Ar gas profiles were measured which exhibited seasonal variations with below atmospheric values when the soil was warming in spring/summer and above atmospheric values when groundwater was cooling in fall/winter. Both abiotic and biotic processes contributed to the excess N2 and N2O that was observed. The current data indicate that large concentrations of excess N gases can accumulate within soil, groundwater, and streams of agriculturally dominated watersheds. When excess N gases are exchanged with the atmosphere, the net fluxes to the atmosphere may represent an important loss term for watershed N budgets.
Multiple birth remains prevalent, with prematurity and subsequent disability being common complications. However, little is known of the experiences of mothers living with the combined circumstances of multiple birth, prematurity, and special needs. This paper reports an exploratory study using the qualitative technique of thematic analysis, to describe and interpret the experiences of 10 mothers of prematurely born multiple birth children with diverse special needs. Mothers were shocked to learn they were carrying multiple fetuses, including those who underwent in vitro fertilization with dual embryo transfer. Most experienced protracted concern over one or more babies’ survival during pregnancy, and prescribed bed rest was frequently associated with increased anxiety and other adverse psychological effects. Some experienced disenfranchised grief, such as those grieving the opportunity to bear a single child. The contrast with experiences of mothers of healthy, term singletons caused considerable distress. Feelings of detachment and unreality were common in the immediate postpartum period, possibly due to transient depersonalization. Having more than one newborn created practical and psychological problems during the neonatal period, particularly when infants were separated due to differences in medical status. The extent to which hospitals accommodated the multiple birth relationship varied and significantly affected mothers’ postnatal experiences. Mothers often felt guilty, particularly regarding inequality of care and attention they were able to provide to each child. This was especially problematic for multiples discordant for special needs status. The presence of one normally developing child complicated adjustment to the other's difficulties, and several experienced chronic sorrow. Serious maternal mental health difficulties were common but not universal. Available formal supports were generally perceived as inadequate, addressing some, but not all, of the mothers’ needs. Further work is needed to advance understanding of the relationships between mothers and their multiples, and to explore the implications of special needs within multiple birth families.
The present study aimed to determine the in vitro biological efficacy and selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular amastigotes of Trypanosoma cruzi. The biological activity of these aromatic compounds was assayed for 48 and 24 h against intracellular parasites and bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were also performed to determine their potential use in blood banks by treating the bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4°C. Toxicity against mammalian cells was evaluated using primary cultures of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death rates were determined by MTT colorimetric assays. Our data demonstrated the outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853, DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar against both parasite forms. All AIAs presented superior efficacy to benznidazole and some, such as DB1868, also demonstrated promising activity as a candidate agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these novel AIAs against T. cruzi stimulates further in vivo studies and justifies the screening of new analogues with the goal of establishing a useful alternative therapy for Chagas disease.
High quality ZnSe:Cl has been grown on GaAs by gas source molecular beam epitaxy (GSMBE); elemental Zn and H2Se are used as source materials, with ZnCl2 as a dopant source for donors. Atomic Cl concentrations ([Cl]) approaching 1020 cm−3 have been incorporated into the lattice as indicated by secondary ion mass spectrometry (SIMS). At incorporation levels greater than 1020 cm−3, an appreciable decrease in the growth rate has been observed. The sharp transition to a negligible growth rate is attributed to the occurrence of a surface chemical reaction originating from Cl and H which are present in the GSMBE environment. For [Cl] as high as 4 x 1018 cm−3, the films exhibited high crystalline quality, as indicated by photoluminescence originating from a single intense donor-bound excitonic transition. Hydrogenation of semiconductors can potentially result in the electrical passivation of incorporated acceptor and donor species. In the case of ZnSe:Cl, H was present in the ZnSe layers, but did not appear to adversely affect the electrical properties of the n-type films. In contrast, for the growth of ZnSe:N, where a nitrogen plasma cell was employed as a source of nitrogen, the H concentration (as determined by SIMS) was observed to track the N concentration. The ZnSe:N films were highly resistive for various amounts of N incorporation, which suggests that H incorporation is an issue of primary importance in the p-type doping of ZnSe grown by GSMBE.