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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.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Increasing attention is currently focused on the generation of characteristic x-ray by proton irradiation. This has the advantage of yielding “clean” x-ray- i. e. free from background brerasstrahlung radiation, from even the lightest elements. The disadvantage is that the yields are naturally much lower than those produced by electrons of the same energy. A recent study has extended characteristic x-ray production to a variety of heavy ions and has shown that the cross- sections for the production of clean x-rays are often higher , by as much as several orders of magnitude, than those produced by protons of the same energy. In addition, there has emerged a further advantage, viz. the ability of specially chosen heavy ions to excite characteristic x-ray from a particular element in a selective manner. Since heavy ions penetrate only a few hundred Angstroms in to most solids, the phenomenon can be used as the basis of a technique for the examination of surface deposits, or to measure depth distributions of impurities. For example, Kr ions can be used t o determine the range distribution of antimony which had been implanted in to silicon at 100 keV. The antimony concentration was determined as a function of ∼ 150 Å steps, and was found to exhibit a maximum concentration of ∼ 1 part in 103 of silicon at 450 Å below the surface, falling to zero concentration at ∼2000 Å a depth. In the past, in order to obtain the required degree of sensitivity, such range determinations have relied on radio active tracer techniques.
An entirely new type of proportional counter has been developed during the course of these studies. This instrument, because of its special construction, can be positioned very close to targets in non-dispersive studies, so as to collect the highest possible fraction of emitted x-ray. It incorporates a replaceable anode unit, together with a built- in miniature head amplifier, and exhibits extremely good performance, particularly for ultra-soft x-ray. In addition, rotation of a dial on the end of the counter body allows alteration of the active gas volume during operation, and so permits tuning into x-rays of a particular energy.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
J. E. Colwell, University of Central Florida Orlando, Florida, USA,
J. Blum, Technische Universität Braunschweig Braunschweig, GERMANY,
R. N. Clark, Planetary Science Institute Tucson, Arizona, USA,
S. Kempf, University of Colorado Boulder, Colorado, USA,
R. M. Nelson, Planetary Science Institute Tucson, Arizona, USA
The surface area of Saturn's rings is greater than that of any of the planets in the solar system, yet, aside from dust, we have never observed or sampled an individual ring particle. Rings are unique in the solar system in that they are a complex dynamical system whose individual constituents interact not only with the light that we use to sense them remotely, but also with each other through gravitational and contact forces. These dynamical interactions play as large a role in determining the appearance of the ring system as do the optical properties of the individual ring particles. In this chapter we review the experimental work that has been done to help us understand both aspects of planetary rings: their collective dynamical behavior and their optical properties.
We have a wealth of data on the behavior of ensembles of particles, both dynamically and their optical properties. Laboratory measurements of the behavior of various likely ring particle analogs are a critical link in connecting these bulk observations with the nature of individual ring particles, and understanding the properties of individual ring particles should provide clues to the outstanding unanswered questions about the age and origin of rings.
Images of Saturn's rings and optical depth profiles from occultations show features at a variety of spatial scales, from the resolution limit of tens of meters for occultations up to thousands of kilometers, and including most scales in between (Colwell et al., 2009; Chapter 3). A frustratingly small fraction of these structures is well understood. Many that remain puzzling, such as the large optical depth fluctuations in Saturn's central B ring, the complex structure in the B ring and the inner A ring, the long-wavelength low-amplitude undulations in optical depth in the C ring, and the plateaus in the C ring, are likely linked to either the collective behavior of the ring particles governed in part by their collisional properties (see e.g. Schmidt et al., 2009, for a review) or by ballistic transport of material due to extrinsic micrometeoroid bombardment (Chapter 9). The mechanical properties of individual ring particles are critical in both types of process.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Methane formation in the rumen represents a substantial loss of energy to the animal and is also a major source of greenhouse gas emissions from agriculture. Methanogenesis is the main means of disposal of hydrogen during rumen fermentation. The formation of propionate represents an alternative route of hydrogen disposal, providing sufficient propionate precursors are available. Theoretically, adding propionate precursors should stimulate propionate production and decrease methane production. In the present experiment, the effects of two potential precursors of propionate, fumarate and acrylate, on rumen fermentation and methane production were investigated in a rumen simulating fermentor.
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.
Patient-reported outcomes and epidemiological studies in adults with tetralogy of Fallot are lacking. Recruitment and longitudinal follow-up investigation across institutions is particularly challenging. Objectives of this study were to assess the feasibility of recruiting adult patients with tetralogy of Fallot for a patient-reported outcomes study, describe challenges for recruitment, and create an interactive, online tetralogy of Fallot registry.
Adult patients living with tetralogy of Fallot, aged 18–58 years, at the University of North Carolina were identified using diagnosis code query. A survey was designed to collect demographics, symptoms, history, and birth mother information. Recruitment was attempted by phone (Part I, n=20) or by email (Part II, n=20). Data analysis included thematic grouping of recruitment challenges and descriptive statistics. Feasibility threshold was 75% for recruitment and for data fields completed per patient.
In Part I, 60% (12/20) were successfully contacted and eight (40%) were enrolled. Demographics and birth mother information were obtained for all enrolled patients. In Part II, 70% (14/20) were successfully contacted; 30% (6/20) enrolled and completed all data fields linked to REDCap database; the median time for survey completion was 8 minutes. Half of the patients had cardiac operations/procedures performed at more than one hospital. Automatic electronic data entry from the online survey was uncomplicated.
Although recruitment (54%) fell below our feasibility threshold, enrolled individuals were willing to complete phone or online surveys. Incorrect contact information, privacy concerns, and patient-reported time constraints were challenges for recruitment. Creating an online survey and linked database is technically feasible and efficient for patient-reported outcomes research.
Population-based registries report 95% 5-year survival for children undergoing surgery for CHD. This study investigated paediatric cardiac surgical outcomes in the Australian indigenous population.
All children who underwent cardiac surgery between May, 2008 and August, 2014 were studied. Demographic information including socio-economic status, diagnoses and co-morbidities, and treatment and outcome data were collected at time of surgery and at last follow-up.
A total of 1528 children with a mean age 3.4±4.6 years were studied. Among them, 123 (8.1%) children were identified as indigenous, and 52.7% (62) of indigenous patients were in the lowest third of the socio-economic index compared with 28.2% (456) of non-indigenous patients (p⩽0.001). The indigenous sample had a significantly higher Comprehensive Aristotle Complexity score (indigenous 9.4±4.2 versus non-indigenous 8.7±3.9, p=0.04). The probability of having long-term follow-up did not differ between groups (indigenous 93.8% versus non-indigenous 95.6%, p=0.17). No difference was noted in 30-day mortality (indigenous 3.2% versus non-indigenous 1.4%, p=0.13). The 6-year survival for the entire cohort was 95.9%. The Cox survival analysis demonstrated higher 6-year mortality in the indigenous group – indigenous 8.1% versus non-indigenous 5.0%; hazard ratio (HR)=2.1; 95% confidence intervals (CI): 1.1, 4.2; p=0.03. Freedom from surgical re-intervention was 79%, and was not significantly associated with the indigenous status (HR=1.4; 95% CI: 0.9, 1.9; p=0.11). When long-term survival was adjusted for the Comprehensive Aristotle Complexity score, no difference in outcomes between the populations was demonstrated (HR=1.6; 95% CI: 0.8, 3.2; p=0.19).
The indigenous population experienced higher late mortality. This apparent relationship is explained by increased patient complexity, which may reflect negative social and environmental factors.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
It is well known that the cosmic ray intensity observed at the Earth's surface presents an 11 and 22-yr variations associated with the solar activity cycle. However, the observation and analysis of this modulation through ground muon detectors datahave been difficult due to the temperature effect. Furthermore, instrumental changes or temporary problems may difficult the analysis of these variations. In this work, we analyze the cosmic ray intensity observed since October 1970 until December 2012 by the Nagoya muon detector. We show the results obtained after analyzing all discontinuities and gaps present in this data and removing changes not related to natural phenomena. We also show the results found using the mass weighted method for eliminate the influence of atmospheric temperature changes on muon intensity observed at ground. As a preliminary result of our analyses, we show the solar cycle modulation in the muon intensity observed for more than 40 years.
We aim to discover the accuracy of photometric mass ratios (qph) determined for eclipsing binary stars, in the case of the system having at least one ‘flat bottom’ as a minimum profile, as well as the accuracy of data used in that sense. Within this context, we present the results of two-dimensional grid search (q – i) for some W UMa-type eclipsing binaries showing total eclipses, based on the high precision photometric data provided by the KEPLER Mission. The radial velocity data obtained for KIC10618253 in this study, enables us to compare both qph and the corresponding spectroscopic mass ratio (qsp) values. The results indicate that the high precision photometric data for overcontact eclipsing binaries showing total eclipses allow us to obtain the photometric mass ratios as accurate as the spectroscopic values.
The accuracy of AMS radiocarbon determinations on very small samples has been tested by measuring a suite of microgram-sized samples of a known-age material. The total measurement precision for the smallest sample (50μg) was found to be ± 3% and the precision improved with larger sample size. The accuracies of the measurements were found to be within the measurement precisions.
We report here the first radiocarbon dating of blood residues on prehistoric stone tools. The residues found on two stone artifacts were subjected to various exploratory biochemical techniques to identify the species from which they were derived and to separate a suitable sample for dating by accelerator mass spectrometry. Although these techniques need much further development and detailed testing, the ages obtained in this first study were consistent with other data, indicating that the concept is viable. For the first time, the time of use of stone tools has been found directly, rather than by stratigraphic or other archaeologic inferential techniques.
A re-evaluation of the Longin collagen-extraction method shows that a lower reflux temperature reduces degradation of protein (“collagen”) remnants. This allows additional purification through ultrafiltration to isolate the >30kDalton fraction of the reflux product.
We present a survey of carbon beam yields from 20 simple carbon compounds using a caesium sputter source and the McMaster University tandem accelerator. The carbon yield was measured as a 35MeV 12C4+ beam. We found that the beam intensities could be related to a grouping of the carbides according to the chemical bonding of the compounds. The usefulness of the compounds for accelerator 14C dating was further related to their preparation chemistries. Strontium carbide was the equal of graphite in negative carbon ion beam production and aluminum carbide was found to be a good candidate for further tests because of its good sputter yield and preparation chemistry. Charcoal was also tested with varying amounts of silver added as a heat conduction aid.
The levels and sources of the measurement background in an AMS 14C dating system have been studied in detail. The relative contributions to the total background from combustion, graphitization, storage, handling, and from the accelerator were determined by measuring the C concentrations in samples of anthracite coal ranging in size from 15μg to 20mg. The results show that, for the present system, the uncertainty in the background is greater than that due to measurement precision alone for very old or for very small samples. While samples containing 100μg of carbon can yield useful 14C dates throughout the Holocene, 200 to 500μg are required for dating late Pleistocene materials. With the identification of the procedures that introduce contamination, the level and uncertainty of the total system background should both be reducible to the point that 100μg of carbon would be sufficient for dating most materials.
A sample with a 14C concentration estimated to be greater than 30,000 Modern was inadvertently graphitized and measured in an AMS system. No measurable contamination of the cesium sputter ion source was observed. Simple cleaning procedures removed the contamination from the sample preparation system, with the exception of the reaction vessel in which the sample was graphitized. Sample cross-contamination factors were estimated for all of the preparation and measurement procedures.