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.
Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26–28 weeks’ gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother–infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child’s cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148–220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI −0·70, −0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI −0·69, −0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.
To determine the relationship between falls and deficits in specific cognitive domains in older adults.
An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.
United Kingdom community-based.
5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.
Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.
Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65–0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96–1.00; p = 0.05) remained significant for predicting recurrent falls.
The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.
While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.
In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.
Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.
Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The correlation between objective and subjective nasal obstruction is poor, and dissatisfaction rates after surgery for nasal obstruction are high. Accordingly, novel assessment techniques may be required. This survey aimed to determine patient experience and preferences for the measurement of nasal obstruction.
Prospective survey of rhinology patients.
Of 72 questionnaires distributed, 60 were completed (response rate of 83 per cent). Obstruction duration (more than one year) (χ2 = 13.5, p = 0.00024), but not obstruction severity, affected willingness to spend more time being assessed. Questionnaires (48 per cent) and nasal inspiratory peak flow measurement (53 per cent) are the most commonly used assessment techniques. Forty-nine per cent of participants found their assessment unhelpful in understanding their obstruction. Eighty-two per cent agreed or strongly agreed that a visual and numerical aid would help them understand their blockage.
Many patients are dissatisfied with current assessment techniques; a novel device with visual or numerical results may help. Obstruction duration determines willingness to undergo longer assessment.
Struggles managing conflict and hostility in adolescent social relationships were examined as long-term predictors of immune-mediated inflammation in adulthood that has been linked to long-term health outcomes. Circulating levels of interleukin-6 (IL-6), a marker of immune system dysfunction when chronically elevated, were assessed at age 28 in a community sample of 127 individuals followed via multiple methods and reporters from ages 13 to 28. Adult serum IL-6 levels were predicted across periods as long as 15 years by adolescents’ inability to defuse peer aggression and poor peer-rated conflict resolution skills, and by independently observed romantic partner hostility in late adolescence. Adult relationship difficulties also predicted higher IL-6 levels but did not mediate predictions from adolescent-era conflict struggles. Predictions were also not mediated by adult trait hostility or aggressive behavior, suggesting the unique role of struggles with conflict and hostility from others during adolescence. The implications for understanding the import of adolescent peer relationships for life span physical health outcomes are considered.
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 LOFAR Tied Array All-Sky Survey (LOTAAS) is an ongoing all northern sky survey for pulsars and transients. It is one of the first large scale pulsar surveys conducted at an observing frequency below 200 MHz. The unique set-up of the survey is the simultaneous formation of 222 beams for each survey pointing by coherently adding signals from the central 6 LOFAR stations. This represents the first SKA-like pulsar survey. As of 12 September 2017, the survey has completed 1456 pointings, more than two-thirds of the total. The survey has discovered 61 new pulsars via Fourier-based periodicity searches and a further 5 via single pulse searches. I present the survey approach and distinctive features including a discussion of an improved machine learning classifier used to identify the best candidates produced by the pipeline for further investigation. I present a summary of the discoveries so far including the first binary pulsar and the pulsar with the longest spin period of 23.5 s.
Faster eating rates are associated with increased energy intake, but little is known about the relationship between children’s eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children’s BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.
Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987–1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3·79%; 3·47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8·41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBs-positive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55·13 mIU/ml and this declined after immunization. Fewer than 2·0% of participants had anti-HB levels ⩾1000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.
Dilute magnetic semiconductors are attractive due to their potential in spintronic devices. In this work, vanadium doped ZnO system has been studied to see its future as a dilute magnetic semiconductor. Vanadium doped ZnO thin films where vanadium percentage is 2, 3, and 5% are deposited by pulsed laser technique (PLD). The lattice parameter c derived from the (002) diffraction peak increases as vanadium content increases, suggesting vanadium substitution for Zn in ZnO lattice. Photoluminescence (PL) measurements at low temperature shows the emission peak at 3.30 eV which hint toward p-type doping in ZnO. X-ray photoelectron spectroscopy (XPS) results show that vanadium exists in V2+ and V4+ valence state, which is in agreement with the XRD and PL results and support the vanadium doped ZnO phase. The ferromagnetic behavior also supports the formation of vanadium doped ZnO phase in thin film samples.
Neurological soft signs (NSS) have long been considered potential endophenotypes for schizophrenia. However, few studies have investigated the heritability and familiality of NSS. The present study examined the heritability and familiality of NSS in healthy twins and patient–relative pairs.
The abridged version of the Cambridge Neurological Inventory was administered to 267 pairs of monozygotic twins, 124 pairs of dizygotic twins, and 75 pairs of patients with schizophrenia and their non-psychotic first-degree relatives.
NSS were found to have moderate but significant heritability in the healthy twin sample. Moreover, patients with schizophrenia correlated closely with their first-degree relatives on NSS.
Taken together, the findings provide evidence on the heritability and familiality of NSS in the Han Chinese population.
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.
Mn-doped CeO2 electrolytes formulated as Ce1-xMnxO2-x (0.05 ≤ x ≤ 0.25) were prepared via soft chemical technique which involved co-precipitation of Mn2+ and Ce4+ using oxalic acid as the precipitant. The optimized pH for a stable incorporation of Mn dopant into ceria was found to be pH = 10. The solubility limit of MnO in the CeO2 fluorite lattice structure was suggested to be x = 0.20. The phase composition, morphology properties and elemental analysis of the oxalate and derived-powder was characterized using X-ray diffraction, SEM and X-ray fluorescence (XRF) respectively. The electrical conductivity of sintered samples of Mn-doped CeO2 ceramics were investigated in air using AC impedance spectroscopy. The bulk conductivities of the Mn-doped CeO2 ceramics sintered at 1200 °C at a test temperature of 800 °C were determined to be 4.223 x 10-4 ohm-1 cm-1 for Mn content x = 0.10 with activation energy, Ea = 0.88 eV.