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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.
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.
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.
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
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.
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 tested a simple method for removing a collagen-based glue preservative from bone destined for radiocarbon and stable isotope analyses. The method is sufficient for bone samples from which only stable isotope measurements are required. For 14C dating, such samples of age less than about 10 ka can be adequately dated, but for older samples, the circumstances must be carefully evaluated.
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.
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 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.
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.
Radiocarbon dates from sediment core samples are usually obtained on the whole organic carbon portion in order to use as little of the valuable sediment as possible. Such measurements may not result in an accurate chronology of the sediment because the material may include carbon from different reservoirs at the time of deposition. The development of AMS techniques for dating ultra-small (20–500μg) carbon samples permits dating various components of cored sediments. We give examples of physical and chemical fractions of sediments which illustrate the large differences in ages obtainable from materials at the same sediment depth. The dating of all or several of these fractions demands more complex interpretations than just the derivation of a sedimentation rate from whole organic carbon dates.
Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.
ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.
This paper presents the rationale for the study and presents a summary of the study design.
ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.
The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.