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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.
To explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.
Retrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.
The study included 27 transplant centers in freestanding children’s hospitals.
The primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital antibiotic utilization rates were reported as days of therapy (DOTs) per 1,000 neutropenic days. Negative binomial regression was used to estimate hospital utilization rates, adjusting for patient covariates including demographics, transplant characteristics, and severity of illness. To better quantify the magnitude of hospital variation and to explore hospital-level drivers in addition to patient-level drivers of variation, mixed-effects negative binomial models were also constructed.
Adjusted hospital rates of antipseudomonal antibiotic use varied from 436 to 1121 DOTs per 1,000 neutropenic days, and rates of broad-spectrum, gram-positive antibiotic use varied from 153 to 728 DOTs per 1,000 neutropenic days. We detected variability by hospital in choice of antipseudomonal agent (ie, cephalosporins, penicillins, and carbapenems), but gram-positive coverage was primarily driven by vancomycin use. Considerable center-level variability remained even after controlling for additional hospital-level factors. Antibiotic use was not strongly associated with days of significant illness or mortality.
Among a homogenous population of children undergoing HCT for acute leukemia, both the quantity and spectrum of antibiotic exposure in the immediate posttransplant period varied widely. Antimicrobial stewardship initiatives can apply these data to optimize the use of antibiotics in transplant patients.
Muscularity of lamb carcasses, which is defined as the depth of muscle relative to dimensions of the skeleton (De Boer et al., 1974), is a commercially important trait in many countries. An objective index of muscularity was defined by Purchas et al. (1991) based on the weights of the muscles around a bone and the bone length. Jones et al. (2002) proposed an objective index to assess in vivo the shape of the muscle in the hind leg using X-ray Computed Tomography (CT), which had a phenotypic correlation of 0.63 with dissection measures of muscularity, as described by Purchas et al. (1991).
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.
Recent analysis pointed towards visual imaging analysis (VIA), which yields pig body size measures and shape indices from two-dimensional visual images of living pigs, as a potential technique for estimating fat and lean content in pig carcasses (Doeschl et al., 2004). The present analysis further explored the potential of using VIA body size and shape indices as indicators of the proportion of lean and fat in various carcass joints, either alone or in combination with ultrasonic backfat depth of the live animal. Due to increasing interest in the shape of retail cuts in the meat industry, the association between VIA size measures and the dimensions of the longissimus dorsi and gluteobiceps muscles is also assessed.
Visual imaging systems provide daily plan (overhead) measurements of pigs. These allow monitoring and control of pig growth, as is essential to production efficiency. Schofield et al., 1999 suggest that size measurements can provide accurate estimates of live weight, but a description of growth in terms of size and shape may also give a direct quantification of body form and value. This report presents analyses of the growth of pigs of two commercial breed types in terms of live weight, body plan area and ham width, and examines the relationship between observed body shapes of living pigs and their dissected body composition.
Modern retailing of venison through supermarkets requires that the product be on the shelf for an extended period compared with the traditional short season in autumn/early winter. However, deer are highly seasonal animals and a range of strategies is needed to increase marketing opportunities for venison. One strategy utilizes extended winter daylength and high levels of nutrition to advance the slaughter season (Davies, 1995; Fisher et al., 1995). Another strategy is to adopt more natural, low input systems with reduced production costs, in which deer reach slaughter condition during their third summer at 22-26 months of age, but this needs full investigation. This study involved sequential slaughtering of deer to ascertain how rapidly carcass composition and meat quality changes over this period.
Psychotic symptoms are common in children and adolescents and may be early manifestations of liability to severe mental illness (SMI), including schizophrenia. SMI and psychotic symptoms are associated with impairment in executive functions. However, previous studies have not differentiated between ‘cold’ and ‘hot’ executive functions. We hypothesized that the propensity for psychotic symptoms is specifically associated with impairment in ‘hot’ executive functions, such as decision-making in the context of uncertain rewards and losses.
In a cohort of 156 youth (mean age 12.5, range 7–24 years) enriched for familial risk of SMI, we measured cold and hot executive functions with the spatial working memory (SWM) task (total errors) and the Cambridge Gambling Task (decision-making), respectively. We assessed psychotic symptoms using the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia interview, Structured Interview for Prodromal Syndromes, Funny Feelings, and Schizophrenia Proneness Instrument – Child and Youth version.
In total 69 (44.23%) youth reported psychotic symptoms on one or more assessments. Cold executive functioning, indexed with SWM errors, was not significantly related to psychotic symptoms [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.85–2.17, p = 0.204). Poor hot executive functioning, indexed as decision-making score, was associated with psychotic symptoms after adjustment for age, sex and familial clustering (OR 2.37, 95% CI 1.25–4.50, p = 0.008). The association between worse hot executive functions and psychotic symptoms remained significant in sensitivity analyses controlling for general cognitive ability and cold executive functions.
Impaired hot executive functions may be an indicator of risk and a target for pre-emptive early interventions in youth.
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.
The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients.
This study involved 236 FEP cases aged 18–65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire.
Childhood sexual abuse [β = 0.96, 95% confidence interval (CI) 0.40–1.52], childhood physical abuse (β = 0.48, 95% CI 0.03–0.93) and parental separation (β = 0.60, 95% CI 0.10–1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (β = 0.36, 95% CI 0.08–0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions.
A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA–psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.
First-order modeling suggests that a low-water phase in late-glacial Lake Agassiz can be explained through changes in the balance between evaporation, precipitation, and runoff, rather than drainage. The low-water Moorhead Phase is often attributed to drainage through outlets opened by isostatic depression and retreat of the Laurentide ice margin. However, new data indicate that the proposed outlets were ice-covered during the Moorhead Phase. Instead, the lake water levels dropped to the Moorhead Phase before the start of the Younger Dryas chronozone and remained there until 11.3 ka. Thus, drainage seems to be an implausible explanation for Younger Dryas-aged low water levels in Lake Agassiz. An alternative explanation is that evaporation equaled or exceeded water inputs from the adjacent ice margin and the deglaciated parts of the drainage basin. To evaluate whether this hypothesis is plausible, we constructed a simple model that considers the paleo-basin geometry, hydrology, and meltwater production from the adjacent ice margin. Modest hydrologic changes (within the range of present-day variability), coupled with low meltwater production, produce a closed basin. Shifts in the location of the polar jet, driven by increased Arctic albedo, may explain our inferred hydrologic changes.
Four traditionally recognized strandline complexes in the southern basin of glacial Lake Agassiz are the Herman, Norcross, Tintah and Campbell, whose names correspond to towns in west-central Minnesota that lie on a linear transect defined by the Great Northern railroad grade; the active corridor for commerce at the time when Warren Upham was mapping and naming the shorelines of Lake Agassiz (ca.1880–1895). Because shorelines represent static water planes, their extension around the lake margin establishes time-synchronous lake levels. Transitions between shoreline positions represent significant water-level fluctuations. However, geologic ages have never been obtained from sites near the namesake towns in the vicinity of the southern outlet. Here we report the first geologic ages for Lake Agassiz shorelines obtained at field sites along the namesake transect, and evaluate the emerging chronology in light of other paleoclimate records. Our current work from 11 sampling sites has yielded 16 independent ages. These results combined with a growing OSL age data set for Lake Agassiz's southern basin provide robust age constraints for the Herman, Norcross and Campbell strandlines with averages and standard deviations of 14.1 ± 0.3 ka, 13.6 ± 0.2 ka, and 10.5 ± 0.3 ka, respectively.
Inflammation is associated with preterm premature rupture of membranes (PPROM) and adverse neonatal outcomes. Subchorionic thrombi, with or without inflammation, may also be a significant pathological finding in PPROM. Patterns of inflammation and thrombosis may give insight into mechanisms of adverse neonatal outcomes associated with PPROM. To characterize histologic findings of placentas from pregnancies complicated by PPROM at altitude, 44 placentas were evaluated for gross and histological indicators of inflammation and thrombosis. Student's t-test (or Mann–Whitney U-test), χ2 analysis (or Fisher's exact test), mean square contingency and logistic regression were used when appropriate. The prevalence of histologic acute chorioamnionitis (HCA) was 59%. Fetal-derived inflammation (funisitis and chorionic plate vasculitis) was seen at lower frequency (30% and 45%, respectively) and not always in association with HCA. There was a trend for Hispanic women to have higher odds of funisitis (OR = 5.9; P = 0.05). Subchorionic thrombi were seen in 34% of all placentas. The odds of subchorionic thrombi without HCA was 6.3 times greater that the odds of subchorionic thrombi with HCA (P = 0.02). There was no difference in gestational age or rupture-to-delivery interval, with the presence or absence of inflammatory or thrombotic lesions. These findings suggest that PPROM is caused by or can result in fetal inflammation, placental malperfusion, or both, independent of gestational age or rupture-to-delivery interval; maternal ethnicity and altitude may contribute to these findings. Future studies focused on this constellation of PPROM placental findings, genetic polymorphisms and neonatal outcomes are needed.
We use spectroscopic imaging to investigate the enhancement of infra-red to visible upconversion in rare-earth doped nano-particles (NaYF4:Yb:Er) supported on nano-fabricated plasmonic substrates consisting of square lattices of Au nano-pillars fabricated by electron beam lithography and designed to support a surface plasmon polariton at frequencies which are nearresonant with the rare-earth ion (Yb3+) absorption. We observe a systematic enhancement in the efficiency of upconversion associated with the interaction of the co-doped nano-particles with the plasmonic substrate. Spectrally-resolved imaging provides a massively parallel means of assessing the range of achievable enhancement and its relation to the specific configuration of the substrate / upconverting nano-particle system. Spectrally-resolved reflectivity of the plasmonic substrates confirms the role of the surface plasmon polariton in the upconversion enhancement. Experimental results are compared to Finite Difference Time Domain simulations of the frequency-dependent reflectivity of these metallic nanostructures.
The ability to strongly attach biomolecules such as enzymes and antibodies to surfaces underpins a host of technologies that are rapidly growing in utility and importance. Such technologies include biosensors for medical and environmental applications and protein or antibody diagnostic arrays for early disease detection. Emerging new applications include continuous flow reactors for enzymatic chemical, textile or biofuels processing and implantable biomaterials that interact with their host via an interfacial layer of active biomolecules. In many of these applications it is desirable to maintain physical properties of an underlying material whilst engineering a surface suitable for attachment of proteins or peptide constructs. Nanoscale polymeric interlayers are attractive for this purpose.
We have developed interlayers that form the basis of a new biomolecule binding technology with significant advantages over other currently available methods. The interlayers, created by the ion implantation of polymer like surfaces, achieve covalent immobilization on immersion of the surface in protein solution. The interlayers can be created on any underlying material and ion stitched into its surface. The covalent immobilization of biomolecules from solution is achieved through the action of highly reactive free radicals in the interlayer.
In this paper, we present characterisation of the structure and properties of the interlayers and describe a detailed kinetic model for the covalent attachment of protein molecules directly from solution.
Ba0.6Sr0.4TiO3 films were grown by molecular beam epitaxy on MgO(001) and LaAlO3(001) substrates. The growth mode was determined to be two-dimensional by in-situ reflection high-energy electron diffraction. The films were structurally and dielectrically characterized ex-situ using X-ray diffraction, Rutherford backscattering spectrometry, and split cavity resonance mode dielectrometry. The structural and dielectric properties of the Ba0.6Sr0.4TiO3 film grown on MgO were determined to be inferior to the film grown on LaAlO3, as was indicated by the broader rocking curve (0.59 deg. vs. 0.17 deg.) and higher dielectric loss (0.29 vs. 0.12).
The measurement of single-crystal elastic properties is an important method of materials characterization. Elastic properties define intrinsically bulk behavior, but they also provide a microscopic insight into the dynamical behavior of the crystal lattice in relation to crystal structure and bonding. Moreover, they are particularly informative probes into the onset and the nature of a lattice instability and its role in inducing a phase transformation. On a macroscopic scale, stress-strain relationships, particularly those of an anisotropic kind, can be better understood and described in terms of the single-crystal elastic constants.
Failure of ceramic-metal interfaces induced by residual or applied stress is often brittle in nature although plastic strain in one or more bonding layers may add to the fracture energy for decohesion. Thus, the fracture toughness depends on chemical bonding across the interface, the plasticity and flow stress of the metal as well as other factors, arising from local internal stresses and the microstructure of the ceramic-metal couple, that cause crack tip branching, deflection, bridging, blunting or shielding. Electron microscopy and DCB testing of metal-glass systems provide insights into the relative importance of factors that determine the decohesion resistance.