Book chapters will be unavailable on Saturday 24th August between 8am-12pm BST. This is for essential maintenance which will provide improved performance going forwards. Please accept our apologies for any inconvenience caused.
To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
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’.
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.
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.
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.
Objectives: The aim of this study was to evaluate the reliability and validity of three computerized neurocognitive assessment tools (CNTs; i.e., ANAM, DANA, and ImPACT) for assessing mild traumatic brain injury (mTBI) in patients recruited through a level I trauma center emergency department (ED). Methods: mTBI (n=94) and matched trauma control (n=80) subjects recruited from a level I trauma center emergency department completed symptom and neurocognitive assessments within 72 hr of injury and at 15 and 45 days post-injury. Concussion symptoms were also assessed via phone at 8 days post-injury. Results: CNTs did not differentiate between groups at any time point (e.g., M 72-hr Cohen’s d=−.16, .02, and .00 for ANAM, DANA, and ImPACT, respectively; negative values reflect greater impairment in the mTBI group). Roughly a quarter of stability coefficients were over .70 across measures and test–retest intervals in controls. In contrast, concussion symptom score differentiated mTBI vs. control groups acutely), with this effect size diminished over time (72-hr and day 8, 15, and 45 Cohen’s d=−.78, −.60, −.49, and −.35, respectively). Conclusions: The CNTs evaluated, developed and widely used to assess sport-related concussion, did not yield significant differences between patients with mTBI versus other injuries. Symptom scores better differentiated groups than CNTs, with effect sizes weaker than those reported in sport-related concussion studies. Nonspecific injury factors, and other characteristics common in ED settings, likely affect CNT performance across trauma patients as a whole and thereby diminish the validity of CNTs for assessing mTBI in this patient population. (JINS, 2017, 23, 293–303)
The Pandemic Risk Assessment Model (PRAM) is a mathematical model developed to analyse two pandemic influenza control measures available to public health: antiviral treatment and immunization. PRAM is parameterized using surveillance data from Alberta, Canada during pandemic H1N1. Age structure and risk level are incorporated in the compartmental, deterministic model through a contact matrix. The model characterizes pandemic influenza scenarios by transmissibility and severity properties. Simulating a worst-case scenario similar to the 1918 pandemic with immediate stockpile release, antiviral demand is 20·3% of the population. With concurrent, effective and timely immunization strategies, antiviral demand would be significantly less. PRAM will be useful in informing policy decisions such as the size of the Alberta antiviral stockpile and can contribute to other pandemic influenza planning activities and scenario analyses.
The SFU Archaeology Department has constructed a small radiocarbon dating facility to serve its own needs and, to the extent that time is available, the needs of other archaeologists and earth scientists. All dates reported here were processed by our laboratory from October 1979 to September 1980. The 14C measurements are made using conventional techniques for liquid scintillation counting of benzene. The samples are burned in a Phonon Mark IV combustion bomb and the resultant CO2 is purified and converted to Li2C2 using a reaction vessel based on the design of Polach, Gower, and Fraser (ms). Acetylene is formed by hydrolysis with distilled H2O which has been aged for a minimum of three months. The acetylene is trimerized to benzene with the Mobil Durabead I catalyst. The conversion efficiency of CO2 to C6H6 is typically 95%. Gas chromatographic analysis of typical samples of the synthesized benzene indicates 99.8% purity with toluene produced in trace amounts.
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.
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.
This list reports measurements made on archaeologic and geologic samples by our laboratory from June 1982 to December 1983. Results of measurements made during that period which lack review by submitters will be reported in a subsequent date list. Sample preparation techniques and benzene synthesis remain as described previously (R, 1982, v 24, p 344–351). For low organic samples, such as sediments, we now use a combustion tube assembly. These samples are burned under oxygen flow in a quartz tube. To absorb sulfur and break up nitrous compounds, we pass combustion gases through a 50% mixture of MnO2 and CuO wire heated to ca 500°C. The gas is then bubbled through a distilled water and KMnO4 solution to remove chlorides before being introduced into our standard dry ice and CO2 traps.
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.