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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.
Quantitative X-ray powder diffraction using the complete digitized diffraction pattern has proved to be an effective approach to improving the accuracy of the analysis of complex mineral mixtures, provided representative reference patterns and accurate Reference Intensity Ratio (RIR) factors arc available for each component phase. However, chemical and structural variability of common rock-forming minerals may complicate the pattern fitting approach. A method has been developed which utilizes X-ray fluorescence chemistry of an unknown and realistic compositional ranges for component phases as constraints on the quantitative XRD analysis without significant compromise of the pattern fit. This unique approach no only yields accurate weight fractions, but also provides indications of the specific compositions of each phase present in the mixture.
Maternal exposures to fever and infections in pregnancy have been linked to subsequent psychiatric morbidity in the child. This study examined whether fever and common infections in pregnancy were associated with psychosis-like experiences (PLEs) in the child.
A longitudinal study of 46 184 children who participated in the 11-year follow-up of the Danish National Birth Cohort was conducted. Pregnant women were enrolled between 1996 and 2002 and information on fever, genitourinary infections, respiratory tract infection, and influenza-like illness during pregnancy was prospectively collected in two interviews during pregnancy. PLEs were assessed using the seven-item Adolescent Psychotic-Like Symptom Screener in a web-based questionnaire completed by the children themselves at age 11.
PLEs were reported among 11% of the children. Multinomial logistic regression models with probability weights to adjust for potential selection bias due to attrition suggested that maternal fever, genitourinary infections and influenza-like illness were associated with a weak to moderate increased risk of subclinical psychosis-like symptoms in the offspring, whereas respiratory tract infections were not. No clear pattern was observed between the strengths of the associations and the timing of exposure, or the type of psychosis-like symptom.
In this study, maternal exposures to fevers and common infections in pregnancy were generally associated with a subtle excess risk of PLEs in the child. A more pronounced association was found for influenza-like illness under an a priori definition, leaving open the possibility that certain kinds of infections may constitute important risk factors.
Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.
The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25–70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was −9 and −11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.
Several new AMS 14C dates on shells from the Fossvogur sea sediments in southern Iceland are reported. Up till now, researchers have assumed that the Fossvogur sediments formed during the last interglacial period (Eem), some 100,000 years ago. However, a recent 14C determination from this location yielded an age of ca 11,000 yr. Because of the importance of these sediments for the Quaternary chronology of Iceland, further sampling for 14C dating was subsequently initiated. The present results on several shell samples collected from the Fossvogur layers strongly indicate that these sediments were formed during the warm Allerød period toward the end of the last glaciation.
First results from the 4-6 months observations of the VIRGO experiment (Variability of solar IRradiance and Gravity Oscillations) on the ESA/NASA Mission SOHO (Solar and Heliospheric Observatory) are reported. The time series are evaluated in terms of solar irradiance variability, solar background noise characteristics and p-mode oscillations. The solar irradiance is modulated by the passage of active regions across the disk, but not all of the modulation is straightforwardly explained in terms of sunspot flux blocking and facular enhancement. The observed p-mode frequencies are more-or-less in agreement with earlier measurements, but it is interesting to note that systematic differences seem to exist between the observations in different colours. There is also evidence that magnetic activity plays a significant role in the dynamics of the oscillations beyond its modulation of the resonant frequencies. Moreover, by comparing the amplitudes of different components of p-mode multiplets, each of which are influenced differently by spatial inhomogeneity, we have found that activity enhances excitation.
Research on close binary systems has continued at a high level during the past triennium, although the rate of growth is noticeably slower – probably reflecting the cutbacks in funds to which many of us are subject. There have also been changes of emphasis within the field, which are commented on in the pages that follow. These reflect both changing opportunities for observation and the natural development of the subject. In many areas, the time is ripe for a more critical look at ideas that previously seemed adequate.
This report covers the period June 1981 to June 1984. and includes some material from IAU Colloquium No. 88, October, 1984.). The field of radial velocities has undergone a renaissance in the last few years as the new radial velocity machines have come into use. Not only can stars of much fainter magnitudes be reached, but the precision of the measured radial velocity has been increased by orders of magnitude. Instead of speaking of velocities accurate to kilometers per second it is now possible to measure velocities to tens of meters per second. Research programs, involving these new techniques are now underway involving the study of hundreds, and in some cases, thousands of faint stars.
We have obtained new optical spectra of the radio galaxy 3C 129 and the giant galaxy close to it. From these spectra we deduce a relative radial velocity of 710 km s−1 between the two galaxies. Using the orbit calculations of Byrd & Valtonen (1978) and the new observations we obtain a new value, 3.3 × 1014M⊙, for the mass of the system.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
We assessed the role of tuberculosis (TB) disease and HIV infection on the level of physical activity. A combined heart rate and movement sensor was used to assess habitual physical activity in TB patients and non-TB controls. The association between sputum-negative TB, sputum-positive TB, HIV and physical activity estimates were assessed in multivariable linear regression models adjusted for age, sex, haemoglobin and alpha-1-acid glycoprotein (AGP). Sputum-positive [eB 0·43, 95% confidence interval (CI) 0·29–0·64] and sputum-negative (eB 0·67, 95% CI 0·47–0·94) TB as well as HIV infection (eB 0·59, 95% CI 0·46–0·75) were associated with reduced activity compared to controls. Anaemia accounted for a substantial part of the effects of HIV, while elevated AGP primarily mediated the TB effect. The level of physical activity is highly influenced by TB and HIV, and mainly mediated through anaemia of infection and associated with elevated acute phase response.
This study aims to assess current practices of Canadian physicians providing botulinum toxin-A (BoNT-A) treatments for children with hypertonia and to contrast these with international “best practice” recommendations, in order to identify practice variability and opportunities for knowledge translation.
Thirteen Canadian physicians assembled to develop and analyze results of a cross-sectional electronic survey, sent to 50 physicians across Canada.
Seventy-eight percent (39/50) of physicians completed the survey. The most frequently identified assessment tools were Gross Motor Function Classification System, Modified Tardieu Scale and neurological examination. Goal-setting tools were infrequently utilized. Common indications for BoNT-A injections and the muscles injected were identified. Significant variability was identified in using BoNT-A for hip displacement associated with hypertonia. The most frequent adverse event reported was localized weakness; 54% reporting this “occasionally“ and 15% “frequently”. Generalized weakness, fatigue, ptosis, diplopia, dysphagia, aspiration, respiratory distress, dysphonia and urinary incontinence were reported rarely or never. For dosage, 52% identified 16 Units/kg body weight of Botox® as maximum. A majority (64%) reported a maximum 400 Units for injection at one time. For localization, electrical stimulation and ultrasound were used infrequently (38% and 19% respectively). Distraction was the most frequently used pain-management technique (64%).
Canadian physicians generally adhere to international best practices when using BoNT-A to treat paediatric hypertonia. Two knowledge-translation opportunities were identified: use of individualized goal setting prior to BoNT-A and enhancing localization techniques. Physicians reported a good safety profile of BoNT-A in children.
Weight regain after weight loss is common. In the Diogenes dietary intervention study, a high-protein and low-glycaemic index (GI) diet improved weight maintenance. The objective of the present study was to identify (1) blood profiles associated with continued weight loss and weight regain (2) blood biomarkers of dietary protein and GI levels during the weight-maintenance phase. Blood samples were collected at baseline, after 8 weeks of low-energy diet-induced weight loss and after a 6-month dietary intervention period from female continued weight losers (n 48) and weight regainers (n 48), evenly selected from four dietary groups that varied in protein and GI levels. The blood concentrations of twenty-nine proteins and three steroid hormones were measured. The changes in analytes during weight maintenance largely correlated negatively with the changes during weight loss, with some differences between continued weight losers and weight regainers. Increases in leptin (LEP) and C-reactive protein (CRP) were significantly associated with weight regain (P < 0·001 and P = 0·005, respectively), and these relationships were influenced by the diet. Consuming a high-protein and high-GI diet dissociated the positive relationship between the change in LEP concentration and weight regain. CRP increased during the weight-maintenance period only in weight regainers with a high-protein diet (P < 0·001). In addition, testosterone, luteinising hormone, angiotensinogen, plasminogen activator inhibitor-1, resistin, retinol-binding protein 4, insulin, glucagon, haptoglobin and growth hormone were also affected by the dietary intervention. The blood profile reflects not only the weight change during the maintenance period, but also the macronutrient composition of the dietary intervention, especially the protein level.
The Al-Mg-Si (6xxx-series) alloy system is a precipitation hardened alloy gaining much of its strength from precipitate phases acting as pinning centers for dislocation movement. Five years ago, Zandbergen, Andersen and coworkers identified the crystallography of the so-called β″ phase, one of the main hardening phases, using solely electron microscopy techniques . Later, several other phases have been identified using high resolution microscopy. To solve the crystallography of these phases and to get an increased understanding of the electronic structure and bonding, ab initio modeling has proven to be a valuable tool. We present results from calculations on two recently discovered phases and show how ab initio modeling can give insight into the bonding trends and electronic structure of the phases in this alloy system.