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 firstname.lastname@example.org
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.
We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
There are no estimates of the heritability of phenotypic udder traits in suckler sheep, which produce meat lambs, and whether these are associated with resilience to mastitis. Mastitis is a common disease which damages the mammary gland and reduces productivity. The aims of this study were to investigate the feasibility of collecting udder phenotypes, their heritability and their association with mastitis in suckler ewes. Udder and teat conformation, teat lesions, intramammary masses (IMM) and litter size were recorded from 10 Texel flocks in Great Britain between 2012 and 2014; 968 records were collected. Pedigree data were obtained from an online pedigree recording system. Univariate quantitative genetic parameters were estimated using animal and sire models. Linear mixed models were used to analyse continuous traits and generalised linear mixed models were used to analyse binary traits. Continuous traits had higher heritabilities than binary with teat placement and teat length heritability (h2) highest at 0.35 (SD 0.04) and 0.42 (SD 0.04), respectively. Udder width, drop and separation heritabilities were lower and varied with udder volume. The heritabilities of IMM and teat lesions (sire model) were 0.18 (SD 0.12) and 0.17 (SD 0.11), respectively. All heritabilities were sufficiently high to be in a selection programme to increase resilience to mastitis in the population of Texel sheep. Further studies are required to investigate genetic relationships between traits and to determine whether udder traits predict IMM, and the potential benefits from including traits in a selection programme to increase resilience to chronic mastitis.
Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.
We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.
Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.
Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.
Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
The depletion of neutral helium atoms has been studied in an unmagnetised spherical plasma created by DC discharge in a multidipole confinement field. Knowing the neutral density profile is critical to predicting the equilibrium flow of such plasmas. A model of the emissivity due to electron-impact excitation of neutral atoms in the plasma has been derived and used to fit radiance measurements of several neutral transitions to extract the radial profile of neutral density for plasmas of varying temperature and density. We report a depletion of the core neutral density varying between negligible levels to 80 % of the edge neutral density depending on the input power and fuelling. The corresponding ionisation fraction varies between 30–80 % in the plasma core. A simple neutral diffusion model is sufficient to describe the shape of neutral density profile implied by the radiance measurements. We have used the measurements to include a drag force due to neutral charge-exchange collisions in simulations of driven plasma flow. The simulation predicts a better fit to Mach probe flow measurements when this neutral drag is accounted for. This work shows that accounting for a realistic neutral profile is important to predict the plasma flow geometry and its magnetohydrodynamics (MHD) stability.
Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.
Introduction: Telephone quitlines are an easily accessible and effective means for delivering cessation services including nicotine replacement therapy (NRT). Varenicline (VAR) may show superior quit rates to NRT, but has not been routinely evaluated in the context of quitlines.
Aims: To assess the feasibility of distributing VAR through a quitline, and preliminarily compare cessation rates between participants receiving VAR and NRT.
Methods: Participants were recruited through the New York State Smokers’ Quitline. Those randomised to VAR (n = 200) were instructed to obtain a prescription from their primary care physician (PCP) to be filled by mail through the research pharmacy. Those randomised to NRT (n = 100) were mailed NRT using an existing protocol. Outcome measures were number of submitted prescriptions and dispensed medication kits, and self-reported 7-day point prevalence abstinence at follow-up.
Results: The research pharmacy filled 100% of prescriptions through the quitline. However, only 27% of the VAR Arm submitted a prescription. An intent-to-treat analysis revealed that those receiving NRT were more likely to be abstinent at follow-up than the VAR Arm (OR, 2.42; 95% CI, 1.27–4.60; p < 0.01). The per-protocol analysis, which only included those in the VAR Arm who submitted a prescription, showed no difference in quit rates.
Conclusions: The present protocol resulted in successful delivery of VAR through the quitline, but a sizable proportion of the VAR Arm did not submit a prescription. Self-reported barriers included being unable to obtain a prescription from a PCP. Future studies should explore alternative methods for delivering VAR through quitlines.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
Treatment of medical patients with the inflammatory cytokine, interferon-α (IFN-α), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN-α on mood have been described, but the neuropsychological changes associated with IFN-α treatment are largely unexplored. The aim of the present preliminary study was to assess the effect of IFN-α on measures of emotional processing.
We measured changes in emotional processing over 6–8 weeks in 17 patients receiving IFN-α as part of their treatment for hepatitis C virus infection. Emotional processing tasks included those which have previously been shown to be sensitive to the effects of depression and antidepressant treatment, namely facial expression recognition, emotional categorisation and the dot probe attentional task.
Following IFN-α, patients were more accurate at detecting facial expressions of disgust; they also showed diminished attentional vigilance to happy faces. IFN-α produced the expected increases in scores on depression rating scales, but there was no correlation between these scores and the changes in emotional processing.
Our preliminary findings suggest that IFN-α treatment produces negative biases in emotional processing, and this effect is not simply a consequence of depression. It is possible that increased recognition of disgust may represent a neuropsychological marker of depressive disorders related to inflammation.
The Square Kilometre Array will be an amazing instrument for pulsar astronomy. While the full SKA will be sensitive enough to detect all pulsars in the Galaxy visible from Earth, already with SKA1, pulsar searches will discover enough pulsars to increase the currently known population by a factor of four, no doubt including a range of amazing unknown sources. Real time processing is needed to deal with the 60 PB of pulsar search data collected per day, using a signal processing pipeline required to perform more than 10 POps. Here we present the suggested design of the pulsar search engine for the SKA and discuss challenges and solutions to the pulsar search venture.
Knowledge regarding association of dietary branched-chain amino acid (BCAA) and type 2 diabetes (T2D), and the contribution of BCAA from meat to the risk of T2D are scarce. We evaluated associations between dietary BCAA intake, meat intake, interaction between BCAA and meat intake and risk of T2D. Data analyses were performed for 74 155 participants aged 50−79 years at baseline from the Women’s Health Initiative for up to 15 years of follow-up. We excluded from analysis participants with treated T2D, and factors potentially associated with T2D or missing covariate data. The BCAA and total meat intake was estimated from FFQ. Using Cox proportional hazards models, we assessed the relationship between BCAA intake, meat intake, and T2D, adjusting for confounders. A 20 % increment in total BCAA intake (g/d and %energy) was associated with a 7 % higher risk for T2D (hazard ratio (HR) 1·07; 95 % CI 1·05, 1·09). For total meat intake, a 20 % increment was associated with a 4 % higher risk of T2D (HR 1·04; 95 % CI 1·03, 1·05). The associations between BCAA intake and T2D were attenuated but remained significant after adjustment for total meat intake. These relations did not materially differ with or without adjustment for BMI. Our results suggest that dietary BCAA and meat intake are positively associated with T2D among postmenopausal women. The association of BCAA and diabetes risk was attenuated but remained positive after adjustment for meat intake suggesting that BCAA intake in part but not in full is contributing to the association of meat with T2D risk.
Background: Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. Methods: We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Key Findings: Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Conclusions: Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956–967)
There is a known high prevalence of genetic and clinical syndrome diagnoses in the paediatric cardiac population. These disorders often have multisystem effects, which may have an important impact on neurodevelopmental outcomes. Taken together, these facts suggest that patients and families may benefit from consultation by genetic specialists in a cardiac neurodevelopmental clinic.
This study assessed the burden of genetic disorders and utility of genetics evaluation in a cardiac neurodevelopmental clinic.
A retrospective chart review was conducted of patients evaluated in a cardiac neurodevelopmental clinic from 6 December, 2011 to 16 April, 2013. All patients were seen by a cardiovascular geneticist with genetic counselling support.
A total of 214 patients were included in this study; 64 of these patients had a pre-existing genetic or syndromic diagnosis. Following genetics evaluation, an additional 19 were given a new clinical or laboratory-confirmed genetic diagnosis including environmental such as teratogenic exposures, malformation associations, chromosomal disorders, and single-gene disorders. Genetic testing was recommended for 112 patients; radiological imaging to screen for congenital anomalies for 17 patients; subspecialist medical referrals for 73 patients; and non-genetic clinical laboratory testing for 14 patients. Syndrome-specific guidelines were available and followed for 25 patients with known diagnosis. American Academy of Pediatrics Red Book asplenia guideline recommendations were given for five heterotaxy patients, and family-based cardiac screening was recommended for 23 families affected by left ventricular outflow tract obstruction.
Genetics involvement in a cardiac neurodevelopmental clinic is helpful in identifying new unifying diagnoses and providing syndrome-specific care, which may impact the patient’s overall health status and neurodevelopmental outcome.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
A stochastic risk model was developed to estimate the time elapsed before overcrowding (TOC) or feed interruption (TFI) emerged on the swine premises under movement restrictions during a classical swine fever (CSF) outbreak in Indiana, USA. Nursery (19 to 65 days of age) and grow-to-finish (40 to 165 days of age) pork production operations were modelled separately. Overcrowding was defined as the total weight of pigs on premises exceeding 100% to 115% of the maximum capacity of the premises, which was computed as the total weight of the pigs at harvest/transition age. Algorithms were developed to estimate age-specific weight of the pigs on premises and to compare the daily total weight of the pigs with the threshold weight defining overcrowding to flag the time when the total weight exceeded the threshold (i.e. when overcrowding occurred). To estimate TFI, an algorithm was constructed to model a swine producer’s decision to discontinue feed supply by incorporating the assumptions that a longer estimated epidemic duration, a longer time interval between the age of pigs at the onset of the outbreak and the harvest/transition age, or a longer progression of an ongoing outbreak would increase the probability of a producer’s decision to discontinue the feed supply. Adverse animal welfare conditions were modelled to emerge shortly after an interruption of feed supply. Simulations were run with 100 000 iterations each for a 365-day period. Overcrowding occurred in all simulated iterations, and feed interruption occurred in 30% of the iterations. The median (5th and 95th percentiles) TOC was 24 days (10, 43) in nursery operations and 78 days (26, 134) in grow-to-finish operations. Most feed interruptions, if they emerged, occurred within 15 days of an outbreak. The median (5th and 95th percentiles) time at which either overcrowding or feed interruption emerged was 19 days (4, 42) in nursery and 57 days (4, 130) in grow-to-finish operations. The study findings suggest that overcrowding and feed interruption could emerge early during a CSF outbreak among swine premises under movement restrictions. The outputs derived from the risk model could be used to estimate and evaluate associated mitigation strategies for alleviating adverse animal welfare conditions resulting from movement restrictions.
The crystal structure of gianellaite, [(NHg2)2](SO4)(H2O)x, cubic, F4̄3m, a = 9.521(6) Å V = 863.1(1.6) Å3, Z = 4, was solved by direct methods and refined to an R1 index of 2.1% based on 167 unique observed reflections collected on a three-circle rotating-anode (MoKα X-radiation) diffractometer equipped with multilayer optics and an APEX-II detector. In the structure of gianellaite, nitrogen-centred (NHg4)5+ tetrahedra share all corners to form a framework of tetrahedra with an ordered arrangement of interstitial (SO4)2– tetrahedra that show strong orientational disorder. Infrared spectroscopy in the principal O–H stretching region shows peaks at ∼3300 and 1600 cm–1, indicating the presence of (H2O), the position(s) of which could not be discerned in difference-Fourier maps.
Radiometric and AMS radiocarbon dating of a 6-m sediment core from Loch Ness, Scotland, indicates that it represents perhaps the very end of the Late Pleistocene, and the first ca. 7500 yr of the Holocene. Counts of laminations observed in the Holocene section of the core suggest that they are present in sufficient number to constitute annual laminations (varves), an hypothesis consistent with the pollen record, which contains a sequence of zones representative of the Early, Middle and part of the Late Holocene regional vegetation history. On the basis of BSEM and X-ray studies of sediments, and modern seston trap data, the laminations are believed to be produced by winter floods, which introduce increased silt loading into the Loch. Sediment for the rest of the year is mostly composed of clay-sized material. This hypothesis is being further tested, however, by continuing sedimentological and microfossil studies.
Time-depth relations for the core based on calibrated 14C dates and lamination counts, respectively, illustrate the close correspondence between the two sets of data. The latter are therefore now being used to develop a varve chronology for the Holocene for Loch Ness. This will then in turn be used for further chronological studies, and for investigations of palaeoclimatic variations over the eastern North Atlantic, to which the signal of lamination thickness in the sediments is thought to be particularly sensitive. They may also eventually be used for calibration studies, employing 14C dating of specific carbon compounds, or groups of compounds extracted from the sediment using modern organic geochemical methods.
A new approach for adjusting molecular dynamics results on UO2 thermal conductivity to include phonon-spin scattering has been used to improve calculations on UxPu1−xO2 and UxTh1−xO2. We demonstrate that by including spin scattering a strong asymmetry as a function of uranium actinide fraction, x, is obtained. Greater degradation is shown for UxTh1−xO2 than UxPu1−xO2. Minimum thermal conductivities are predicted at U0.97Pu0.03O2 and U0.58Th0.42O2, although the degradation in UxPu1−xO2 is negligible relative to pure UO2.
This study aimed to determine whether age at introduction of solid foods was associated with feeding difficulties at 3 years of age. The present study was carried out using data from the Southampton Women’s Survey (SWS). Women enrolled in the SWS who subsequently became pregnant were followed-up during pregnancy and postpartum, and the offspring have been studied through childhood. Maternal socio-demographic and anthropometric data and child anthropometric and feeding data were collected through interviews and self-administered questionnaires. When the children were 3 years of age, mothers/carers rated six potential child feeding difficulty questions on a four-point Likert scale, including one general question and five specific feeding difficulty questions. Age at introduction of solids as a predictor of feeding difficulties was examined in 2389 mother–child pairs, adjusting for child (age last breast fed, sex, gestation) and maternal characteristics (parity, pre-pregnancy BMI, age, education, employment, parenting difficulties, diet quality). The majority of mothers/carers (61 %) reported some feeding difficulties (general feeding difficulty question) at 3 years of age, specifically with their child eating enough food (61 %), eating the right food (66 %) and being choosy with food (74 %). Children who were introduced to solids ≥6 months had a lower risk of feeding difficulties (RR 0·73; 95 % CI 0·59, 0·91, P=0·004) than children who were introduced to solids between 4 and 6 months. No other significant associations were found. There were few associations between feeding difficulties in relation to age at introduction of solid foods. However, general feeding difficulties were less common among infants introduced to solid foods ≥6 months of age.
Recently, large-scale trials of behavioural interventions have failed to show improvements in pregnancy outcomes. They have, however, shown that lifestyle support improves maternal diet and physical activity during pregnancy, and can reduce weight gain. This suggests that pregnancy, and possibly the whole periconceptional period, represents a ‘teachable moment’ for changes in diet and lifestyle, an idea that was made much of in the recent report of the Chief Medical Officer for England. The greatest challenge with all trials of diet and lifestyle interventions is to engage people and to sustain this engagement. With this in mind, we propose a design of intervention that aims simultaneously to engage women through motivational conversations and to offer access to a digital platform that provides structured support for diet and lifestyle change. This intervention design therefore makes best use of learning from the trials described above and from recent advances in digital intervention design.