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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.
In this study, we examine how the Guri catfish Genidens genidens uses estuarine and freshwater habitats along the largest South American coastal lagoon, through the chemical analysis of otoliths and microscopic analysis of gonads. Chemical composition (Sr:Ca) of otolith edges allowed distinguishing between individuals who used the estuarine or freshwater compartments of the lagoon. The analysis of core-to-edge chemical profiles of each individual otolith revealed that the population may present two different patterns of habitat use along the lagoon. The ‘type 1’ pattern (89.5%) includes fish who appear to have been born in estuarine waters, whereas ‘type 2’ (9.5%) includes those fish born in fresh water. Nevertheless, juveniles from both patterns appear to migrate to estuarine waters. The gonad analysis shows G. genidens may reproduce in fresh water, as nearly 57% of all sampled fish were found to spawn in the freshwater portion of the lagoon. Also, the otolith core of many adult fish presented freshwater signatures, thus suggesting consistent fresh water use during early life. Our findings based on otolith and gonadal analyses challenge the previous classification of G. genidens as an estuarine resident. Rather, our results allow the suggestion that this species should be placed in the ‘estuarine and fresh water’ guild, which includes both fish completing their life cycles within the estuary and fish who consistently use freshwater habitats.
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.
The St. Louis aerosol was sampled during the period 16-22 August 1973 simultaneously at two locations using cascade impactors for sequential 12-hour samples. The six particle size fractions of each sampling were individually analyzed using PIXE for elements from S to Br and beyond and for heavy elements including Pb which permitted time variations of concentrations and particle size distributions to be followed and related to meteorological changes during the sampling period. In addition, the data were compared with average levels of the elements in coastal north Florida and maritime Bermuda as well as at a third St. Louis site. From this it appeared that some of the concentrations in St. Louis were at natural levels whereas others appeared to be higher and linked to air pollution sources. These relationships and others in this study may lead to criteria for distinguishing between pollutants and natural background in urban aerosols.
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.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The photometric phase curves of Saturn's A and B rings exhibit a sharp peak in reflectance when the phase angle approaches zero, commonly known as the opposition effect. Recent work has suggested that the width and amplitude of the opposition effect may be consistent with coherent backscattering from wavelength-sized grains which cover the surfaces of macroscopic ring particles.
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.
An adolescent male with a recent history of streptococcal pharyngitis presented with severe substernal chest pain, troponin leak, and ST-segment elevation, which are suggestive of acute inferolateral myocardial infarction. The coronary angiogram was normal. The patient was subsequently diagnosed with non-rheumatic streptococcal myocarditis. He was treated with amoxicillin and had excellent recovery. Non-rheumatic streptococcal myocarditis is an important mimic of acute myocardial infarction in young adults.
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.
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 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 effects of environmental factors such as water stress, elevated CO2, or temperature on carbon assimilation and allocation in plants have been studied extensively (Gifford and Evans, 1981; Loomis, Rabbinge, and Ng, 1979; Neales and Incoll, 1968). However, the interactions of these processes are not well understood and cannot be predicted with any degree of confidence. Continuous and simultaneous measurements of photosynthesis, transport, and sink activity have never been made during the short- and long-term responses of live, intact plants to step changes in environmental factors. Thus, direct environmental effects and adaptive responses of plants are generally not distinguished. This results in part from limitation in experimental techniques and protocol used in past studies and the lack of experimental validation of hypotheses and models (eg, Goeschl et al, 1976; Magnuson et al, 1979; Smith et al, 1970) dealing with these problems. This paper describes in detail the components of an integrated technique for studying carbon assimilation, transportation and allocation in intact live plants under any set of environmental conditions, using continuously produced 11CO2.
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.
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.