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Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.
We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.
The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.
The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.
In September 2015, an outbreak of Escherichia coli Phage Type 32 with an indistinguishable multi locus variable number tandem repeat analysis profile was identified in Scotland. Twelve cases were identified; nine primary cases, two secondary and one asymptomatic case. Extensive food history investigations identified venison products containing wild venison produced by a single food business operator as the most likely source of the outbreak. Of the nine primary cases, eight had consumed venison products, and one case had not eaten venison themselves but had handled and cooked raw venison in the household. This was the first reported outbreak of Shiga toxin-producing Escherichia coli (STEC) linked to venison products in the UK, and was also notable due to the implicated products being commercially produced and widely distributed. In contrast, previous venison outbreaks reported from other countries have tended to be smaller and related to individually prepared carcases. The outbreak has highlighted some important knowledge gaps in relation to STEC in venison that are currently been investigated via a number of research studies.
The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.
Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.
The Queen's University of Belfast, Northern Ireland and University of Waikato, Hamilton, New Zealand radiocarbon laboratories have undertaken a series of high-precision measurements on decadal samples of dendrochronologically dated oak (Quercus patrea) and cedar (Libocedrus bidwillii) from Great Britain and New Zealand, respectively. The results show a real atmospheric offset of 3.4 ± 0.6% (27.2 ± 4.7 14C yr) between the two locations for the interval ad 1725 to ad 1885, with the Southern Hemisphere being depleted in l4C. This result is less than the value currently used to correct Southern Hemisphere calibrations, possibly indicating a gradient in Δ14C within the Southern Hemisphere.
Leaf mass per area (MA) is a central ecological trait that is intercorrelated with leaf life span, photosynthetic rate, nutrient concentration, and palatability to herbivores. These coordinated variables form a globally convergent leaf economics spectrum, which represents a general continuum running from rapid resource acquisition to maximized resource retention. Leaf economics are little studied in ancient ecosystems because they cannot be directly measured from leaf fossils. Here we use a large extant data set (65 sites; 667 species-site pairs) to develop a new, easily measured scaling relationship between petiole width and leaf mass, normalized for leaf area; this enables MA estimation for fossil leaves from petiole width and leaf area, two variables that are commonly measurable in leaf compression floras. The calibration data are restricted to woody angiosperms exclusive of monocots, but a preliminary data set (25 species) suggests that broad-leaved gymnosperms exhibit a similar scaling. Application to two well-studied, classic Eocene floras demonstrates that MA can be quantified in fossil assemblages. First, our results are consistent with predictions from paleobotanical and paleoclimatic studies of these floras. We found exclusively low-MA species from Republic (Washington, U.S.A., 49 Ma), a humid, warm-temperate flora with a strong deciduous component among the angiosperms, and a wide MA range in a seasonally dry, warm-temperate flora from the Green River Formation at Bonanza (Utah, U.S.A., 47 Ma), presumed to comprise a mix of short and long leaf life spans. Second, reconstructed MA in the fossil species is negatively correlated with levels of insect herbivory, whether measured as the proportion of leaves with insect damage, the proportion of leaf area removed by herbivores, or the diversity of insect-damage morphotypes. These correlations are consistent with herbivory observations in extant floras and they reflect fundamental trade-offs in plant-herbivore associations. Our results indicate that several key aspects of plant and plant-animal ecology can now be quantified in the fossil record and demonstrate that herbivory has helped shape the evolution of leaf structure for millions of years.
Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31–60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs.
Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated ‘lifetime ever smokers’ of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses.
Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50–0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (rG-SNP = 1.00, s.e. = 0.09, p < 0.00001).
Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.
Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: −0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.
Human campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden.
Two complementary techniques are used to study the electrical transport properties related to the use of diamonds as materials for ionizing radiation detectors. Transient photoconductivity using soft x-rays is used to probe the first few microns of the material, while ionizing particle-excited conductivity is used to probe the entire bulk of the material (1 millimeter). Both techniques measure the mean drift distance of free carriers, or the collection distance d. In addition, transient photoconductivity is able to extract the lifetimes and mobilities of the excited carriers. The collection distance measured by the two methods are in agreement, suggesting the material is homogeneous. At an applied field of 10 kV/cm, d is 25 to 30 microns, and, up to a field of 25 kV/cm, d has not saturated. The lifetime varies between 100 and 600 ps, and the mobility varies between 1000 and 4000 cm2/V-s, the range due to natural variations from sample to sample. The primary defects limiting the lifetime are believed to be nitrogen impurities and dislocations.
Diamond is suitable for use as an ionizing particle detector for high rate, high radiation, and/or chemically harsh environments. A sampling calorimeter, a detector measuring the total energy of an incident particle, consisting of 20 alternating layers of diamond and tungsten has been constructed and tested. The diamond for the detector layers was grown by chemical vapor deposition with an averaged thickness of 500 μm. The active area of each layer was 3×3 cm2 with ohmic contacts on opposite faces forming a metal-insulator-metal structure. The calorimeter was tested with electrons of energies up to 5.0 GeV. The response of the diamond/tungsten calorimeter was found to be linear as a function of incident energy. A direct comparison of diamond/tungsten and silicon/tungsten calorimeters was made.
The electrical properties associated with diamond charged particle- and photo-detectors were studied using charged particle-induced conductivity (CPIC) and photo-induced conductivity (PIC). The collection distance d, the product of the excess carrier mobility μ excess carrier lifetime T and electric field E, was used to characterize the diamonds. X-ray diffraction, Raman spectroscopy, photoluminescence, SEM and TEM were performed on CVD diamond detectors to investigate the limitations of the electrical properties. Correlations were found between the electrical properties and the material characterizations.
Solid state bulk processing techniques were used to synthesize various transparent conducting oxides (TCO's) with In, Zn, and Sn cations. Optical and electronic properties of resultant phase-pure TCO's were compared to each other and to bulk samples of Sn-doped In2O3 (ITO). Reduction and heat treatment showed significant effects on optical and electronic performance, indicating optimization of processing conditions will be required for industrial applications.
Comparison of optical and electronic properties in the series of compounds: ZnkIn2O3+k, k = 3,4,5,7,11 revealed trends correlated with the materials’ internal structure. These layered compounds showed improvement of optical properties at higher Zn contents and improvement in conductivity at higher In contents. The trends suggest these materials may be useful for applications where tradeoffs between conductivity and transparency are acceptable.
We report the development of a new family of electron beam resists based on liquid crystalline polysubstituted derivatives of triphenylene. These new resists show excellent performance in terms of both high resolution and high durability to plasma etching. Films of the derivatives have been produced in a controlled manner via room temperature spin coating on hydrogen terminated silicon substrates. The dissolution behaviour of the derivatives in various organic solvents was altered by exposure to a 20 keV electron beam. The solubility of the derivative hexapentyloxytriphenylene, in polar solvents, was substantially increased by electron doses greater than ∼ 3 × 10-4 C/cm2 (positive tone behaviour). Doses greater than ∼ 2.5 × 10-3 C/cm2 led to negative tone behaviour in both polar and non-polar solvents. Other derivatives also demonstrated a reduction in their dissolution rate for doses between ∼ 1 × 10-3 and ∼ 7 × 10-3 C/cm2. The derivative sensitivity was found to be roughly proportional to the molecular mass. Negative tone patterns were found to have an etch durability ∼ 70 % greater than that of a conventional novolac based negative tone resist (SAL601). The performance of these new resists has been demonstrated by the definition of line and space patterns with a resolution of ∼ 14 nm, whilst structures with an aspect ratio of.∼ 50 to 1 were etched into the silicon substrate.
We report systematic studies of the response of C60 derivatives to electron beam irradiation. Films of fourteen different mono, tris and tetra adduct methanofullerene C60 derivatives were produced by spin coating on hydrogen terminated silicon substrates. Exposure of the films to a 20 keV electron beam substantially altered the dissolution rate of the derivative films in organic solvents such as monochlorobenzene. All of the derivatives exhibited negative tone resist behaviour with sensitivities between ∼ 8.5 × 10-4 and ∼ 4 × 10-3 C/cm2 107, much higher than that of C60. Features with widths of ∼ 20 nm were produced using these compounds, and the etch ratios of the compounds were found to be more than twice those of a standard novolac based resist (SAL601).
During a 15-month period in Scotland a small but important number of human Campylobacter cases (3·2%) arose from 91 putative household outbreaks. Of the 26 outbreaks with known strain composition, 89% were composed of the same MLST which supports the potential use of MLST in public health epidemiology. The number of cases associated with household outbreaks is much larger than general outbreaks and there is some evidence to indicate that there may be secondary transmission, although this is relatively rare.
A point source outbreak of haemorrhagic colitis due to Escherichia coli O 157. H7 producing verocytotoxin (VT), took place following a christening party in Birmingham in June 1987. Twenty-six people were affected, six were admitted to hospital and one developed haemolytic uraemic syndrome: there were no deaths. VT + E. coli O 157. H7 was isolated from 13 (57%) of 23 faecal specimens from affected people and from 3 (9%) of 33 specimens from asymptomatic people. Free VT was detected in the faeces of one further asymptomatic person. Illness was associated with eating turkey-roll sandwiches (P < 0·001) suggesting that cold meats might be an important source of infection.