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To examine prenatal APAP exposure in relation to language development in offspring at 30 months of age.
A population-based pregnancy cohort study including 754 women who enrolled in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8–13. Two exposure measures were used: (1) maternally reported number of APAP tablets taken between conception and enrollment; (2) APAP urinary concentration at enrollment. Language development at 30 months was assessed by nurse's evaluation and parental questionnaire, including the number of words the child used (<25, 25–50 and >50). Main study outcome; parental report of use of fewer than 50 words, termed language delay (LD).
59.2% of women enrolled in weeks 8–13 reported taking APAP between conception and enrollment. APAP was measurable in all urine samples and urinary APAP was correlated with the number of APAP taken during pregnancy (P<0.01). Language delay was more prevalent in boys (12.6%) than girls (4.1%) (8.5% in total). Both the number of APAP tablets and urinary APAP concentration were associated with greater LD in girls but not in boys. The adjusted odds ratio (OR) for LD among girls whose mothers reported >6 vs. 0 APAP tablets was 5.92 (95% confidence interval (CI) 1.10–31.94). The OR for LD in girls whose mothers’ urinary APAP was in the highest compared to the lowest quartile was 10.34 (95% CI 1.37–77.86). While it cannot be ruled out, our available data do not support confounding by indication.
Given the prevalence of prenatal APAP use and the importance of language development, these findings, if replicated, would suggest that pregnant women should limit their use of this analgesic during pregnancy.
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.
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.
Cannabis varies considerably in levels of its two major constituent cannabinoids – (delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Recently, we found evidence that those who smoked cannabis containing detectable levels of CBD had fewer psychotic-like symptoms than those whose cannabis had no CBD. The present study aimed, first, to replicate those findings and, second, to determine whether protective effects of CBD may extend to other harms of cannabis, such as memory impairment and reduced psychological well-being.
A total of 120 current cannabis smokers, 66 daily users and 54 recreational users were classified into groups according to whether analysis of their hair revealed the presence or absence of CBD and high versus low levels of THC. All were assessed on measures of psychosis-like symptoms, memory (prose recall; source memory) and depression/anxiety.
Lower psychosis-like symptoms were found in those whose hair had CBD compared with those without. However, this was seen only in recreational users, who had higher levels of THC in their hair. Higher THC levels in hair were associated with increased depression and anxiety. Prose recall and source memory were poorer in daily users with high THC levels in hair while recognition memory was better in individuals with CBD present in hair.
CBD attenuates the psychotic-like effects of cannabis over time in recreational users. Higher THC negatively impacts on memory and psychological well-being. These findings raise concerns for the harms stemming from use of varieties such as ‘skunk’ (sensimillia), which lack any CBD but currently dominate the supply of cannabis in many countries.
Opioids are the cornerstone medication for the treatment of moderate to severe pain. However, analgesic opioid requirements and the propensity to suffer from aversive opioid effects, including fatal respiratory depression and addiction, vary widely among patients. The factors underlying the substantial response variance remain largely unknown and need clarification for using opioids more effectively in appropriately selected patients. This ongoing study takes advantage of the twin paradigm to estimate the genetic and environmental contributions to inter-individual differences in opioid responses. Evidence of significant heritability will justify more detailed and extensive genomic studies. The enrollment target is 80 monozygotic and 45 dizygotic twin pairs who undergo a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory-type setting, well-defined pharmacodynamic endpoints are measured to quantify pain sensitivity, analgesic opioid effects, and aversive opioid effects including respiratory depression, sedation and reinforcing affective responses. First results obtained in 159 participants provide evidence for the feasibility and utility of this interventional study paradigm to estimate familial aggregation and heritability components of relevant drug effects. Areas highlighted in this report include recruitment strategies, required infrastructure and personnel, selection of relevant outcome measures, drug infusion algorithm minimizing pharmacokinetic variability, and considerations for optimizing data quality and quantity without hampering feasibility. Applying the twin paradigm to complex and potentially harmful studies comprehensively characterizing pharmacological response profiles is without much precedent. Methods and first results including heritability estimates for heat and cold pain sensitivity should be of interest to investigators considering similar studies.
The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of 1989–90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21–92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups.
Gyps vulture populations across the Indian subcontinent collapsed in the 1990s and continue to decline. Repeated population surveys showed that the rate of decline was so rapid that elevated mortality of adult birds must be a key demographic mechanism. Post mortem examination showed that the majority of dead vultures had visceral gout, due to kidney damage. The realisation that diclofenac, a non-steroidal anti-inflammatory drug potentially nephrotoxic to birds, had become a widely used veterinary medicine led to the identification of diclofenac poisoning as the cause of the decline. Surveys of diclofenac contamination of domestic ungulate carcasses, combined with vulture population modelling, show that the level of contamination is sufficient for it to be the sole cause of the decline. Testing on vultures of meloxicam, an alternative NSAID for livestock treatment, showed that it did not harm them at concentrations likely to be encountered by wild birds and would be a safe replacement for diclofenac. The manufacture of diclofenac for veterinary use has been banned, but its sale has not. Consequently, it may be some years before diclofenac is removed from the vultures' food supply. In the meantime, captive populations of three vulture species have been established to provide sources of birds for future reintroduction programmes.
Double-walled carbon nanotubes (DWNTs), synthesized by the catalytic decomposition of methane, were explored by resonance Raman spectroscopy using different energies for laser excitation. Based on the radial breathing mode frequencies, the indices of the two layers of a DWNT were approximately assigned, depending on the interlayer separation of the two coaxial layers of the DWNT, which ranged from 0.34 to 0.40 nm. From the tentatively assigned results, it was found that the two walls of the DWNT are not strongly selected by chirality and diameter. The results, however, suggest that, for the tubes that are resonant with the available laser excitation energies, most of the outer layers of the observed DWNTs in our samples are semiconducting, while the inner layers of the observed DWNTs are either semiconducting or metallic based on the assembled DWNTs. The characteristics of the G, D, and G′ band of the DWNTs are discussed, and a double peak feature in the D and G′ band, originating from the inner and outer layers of the DWNTs, is reported.
Three different types of carbon nanotubes being considered for bio-recognition experiments were studied using resonance Raman spectroscopy. Raman spectroscopy, taken using several laser excitation energies, has been shown to provide an effective characterization tool for these carbon nanotubes. The technique yields structural information that both complements and corroborates structural information obtained using electron microscopy techniques, such as TEM, SEM, and AFM.
We analyze the dependence of the second-order G'-band profile in terms of their (n,m) indices by measuring the resonance Raman spectra of several semiconducting and metalic isolated single wal carbon nanotubes. We show that this profile is very sensitive to the electronic structure, thus making it possible to get structural (n,m) information and to probe the splitting of the van Hove singularities in the electronic density of states due to the trigona warping effect.
We present results from resonant Raman spectroscopy on the graphite-like G band by measuring Raman spectra on isolated single wal carbon nanotubes (SWNTs). We discuss the G-band lineshape dependence on nanotube diameter and chirality, as well as polarization studies related to the antenna effect. Symmetry selection rules, dipolar and multipolar antenna behaviors are discussed. Spectra at the single nanotube level are related to spectra observed from SWNT bundles.
In 1993 excavations were undertaken at Ochre Brook, Tarbock, about 13 km east of Liverpool, in advance of the construction of the M57–A562 link-road, by R.W. Cowell and R.A. Philpott of the Field Archaeology Section of Liverpool Museum. The work located fragments of two enclosure ditches, a western entrance, and part of the interior of one enclosure, features generally similar to the boundary ditches often associated with rural settlements. However, inside the enclosure was a more or less rectangular building, 11.2 by 5.85–6.9 m in dimensions, its post-holes packed with stone and tile. From pits to the north of the building and from the fills of the enclosure ditches were recovered over 320 kg of apparently unused tile, including many underfired fragments and distorted over-fired waste, as well as burnt clay debris, mostly oxidised. There was, in addition, a relatively small amount of rather crudely made pottery (about 7.5 kg), some underfired. Petrological analyses by David Williams (University of Southampton) suggested that both the pottery and the tile had probably utilised the same basic clay source. Among the mostly orange fired clay debris examined by V.S., were several oxidised fragments of obvious kiln structure, the largest piece comprising the probable junction of the lining-wall of a kiln chamber and its protruding pier or pilaster. Though no actual kiln structure was found in situ in the area excavated, the evidence in toto strongly suggests that tile manufacture had taken place somewhere in the immediate vicinity, with perhaps a small amount of pottery being made simultaneously, in non-commercial quantities.
Results from statutory testing of private water supplies in nine Public Health Laboratories in
England were compiled, and the effects of supply class, source, treatment and location on
water quality were examined. A total of 6551 samples from 2911 supplies was examined, over a
2-year period, of which 1342 (21%) samples, and 949 (33%) supplies on at least one occasion,
failed current regulations for Escherichia coli. Total coliforms, including E. coli, were detected
in 1751 (27%) samples from 1215 (42%) supplies. The percentage of samples positive for E.
coli was highest in summer and autumn, and lowest in winter. Samples taken from larger
supplies and from boreholes were less frequently contaminated than those from other sources.
Chlorination, filtration or UV light treatment improved the bacteriological quality of supplies,
but still resulted in a low level of compliance with the regulations. The public health
implications of the study are discussed.
It has been suggested that a proportion of individuals with a hearing impairment can be fitted with a hearing aid without being otolaryngologically assessed. Such assessments are deemed advisable: (a) to identify otological pathology that might require management and (b) because surgery can be a viable alternative in those with a conductive impairment.
The aim of this study was to prospectively study individuals referred to an Otolaryngology Department in a teaching hospital to assess how technicians, at a direct referral clinic for the provision of a hearing aid, could screen to identify those meriting an otolaryngological opinion. Two hundred and forty-eight patients were evaluated by technicians using strict audiometric and tympanometric criteria. One hundred and twenty-five patients (50 per cent) failed these criteria and were referred to an otologist. The remaining 123 (50 per cent) were managed by technicians but were subsequently reviewed for the purpose of this study by an otologist and their management assessed. In only two patients (one per cent) was it thought that the initial management would have been different if seen by an otologist. Alternative criteria for deciding suitability for management by technicians were applied. The inclusion of tympanometry was essential to avoid missing middle ear pathology.