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Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
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.
Improving quality of life (QOL) for people with dementia is a priority. In care homes, we often rely on proxy ratings from staff and family but we do not know if, or how, they differ in care homes.
We compared 1056 pairs of staff and family DEMQOL-Proxy ratings from 86 care homes across England. We explored factors associated with ratings quantitatively using multilevel modelling and, qualitatively, through thematic analysis of 12 staff and 12 relative interviews.
Staff and family ratings were weakly correlated (ρs = 0.35). Median staff scores were higher than family's (104 v. 101; p < 0.001). Family were more likely than staff to rate resident QOL as ‘Poor’ (χ2 = 55.91, p < 0.001). Staff and family rated QOL higher when residents had fewer neuropsychiatric symptoms and severe dementia. Staff rated QOL higher in homes with lower staff:resident ratios and when staff were native English speakers. Family rated QOL higher when the resident had spent longer living in the care home and was a native English. Spouses rated residents’ QOL higher than other relatives. Qualitative results suggest differences arise because staff felt good care provided high QOL but families compared the present to the past. Family judgements centre on loss and are complicated by decisions about care home placement and their understandings of dementia.
Proxy reports differ systematically between staff and family. Reports are influenced by the rater:staff and family may conceptualise QOL differently.
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.
To determine the patterns and predictors of treatment response trajectories for veterans with post-traumatic stress disorder (PTSD).
Conditional latent growth mixture modelling was used to identify classes and predictors of class membership. In total, 2686 veterans treated for PTSD between 2002 and 2015 across 14 hospitals in Australia completed the PTSD Checklist at intake, discharge, and 3 and 9 months follow-up. Predictor variables included co-morbid mental health problems, relationship functioning, employment and compensation status.
Five distinct classes were found: those with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3%) with a large change. Those with slightly less severe PTSD separated into one class comprising 49.9% of the total sample with large change effects, and a second class comprising 7.9% with extremely large treatment effects. The final class (6.7%) with least severe PTSD at intake also showed a large treatment effect. Of the multiple predictor variables, depression and guilt were the only two found to predict differences in response trajectories.
These findings highlight the importance of assessing guilt and depression prior to treatment for PTSD, and for severe cases with co-morbid guilt and depression, considering an approach to trauma-focused therapy that specifically targets guilt and depression-related cognitions.
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.
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.
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.
We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
Congenital abnormalities of the coronary arteries in the absence of structural heart disease account for a small but interesting percentage of cardiac lesions in children. Their presentation may vary from incidental identification to aborted/sudden cardiac death. Patients with aborted sudden death episodes will require significant support if they develop extensive ischaemic myocardial injury. Ultimately, surgical repair should be carried out as soon as haemodynamic stability is attained and the neurological status is evaluated. The aims of this article were to provide a review of congenital abnormalities of the coronary arteries most commonly seen in children in the ICU as well as to review the current critical-care management thereof.
Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.
Materials and methods
Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.
We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.
Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.
The Wisconsin Plasma Astrophysics Laboratory (WiPAL) is a flexible user facility designed to study a range of astrophysically relevant plasma processes as well as novel geometries that mimic astrophysical systems. A multi-cusp magnetic bucket constructed from strong samarium cobalt permanent magnets now confines a
, fully ionized, magnetic-field-free plasma in a spherical geometry. Plasma parameters of
provide an ideal testbed for a range of astrophysical experiments, including self-exciting dynamos, collisionless magnetic reconnection, jet stability, stellar winds and more. This article describes the capabilities of WiPAL, along with several experiments, in both operating and planning stages, that illustrate the range of possibilities for future users.
Many astrophysical disks, such as protoplanetary disks, are in a regime where non-ideal, plasma-specific magnetohydrodynamic (MHD) effects can significantly influence the behaviour of the magnetorotational instability (MRI). The possibility of studying these effects in the plasma Couette experiment (PCX) is discussed. An incompressible, dissipative global stability analysis is developed to include plasma-specific two-fluid effects and neutral collisions, which are inherently absent in analyses of Taylor–Couette flows (TCFs) in liquid metal experiments. It is shown that with boundary driven flows, a ion-neutral collision drag body force significantly affects the azimuthal velocity profile, thus limiting the flows to regime where the MRI is not present. Electrically driven flow (EDF) is proposed as an alternative body force flow drive in which the MRI can destabilize at more easily achievable plasma parameters. Scenarios for reaching MRI relevant parameter space and necessary hardware upgrades are described.
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and
placental amino acid transporter gene expression have been associated with
development of the offspring in terms of body composition and bone structure.
Several amino acid transporter genes have vitamin D response elements in their
promoters suggesting the possible linkage of these two mechanisms. We aimed to
establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels
relate to expression of placental amino acid transporters. RNA was extracted
from 102 placental samples collected in the Southampton Women's Survey,
and gene expression was analysed using quantitative real-time PCR. Gene
expression data were normalised to the geometric mean of three housekeeping
genes, and related to maternal factors and childhood body composition. Maternal
serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal
25(OH)D and VDBP levels were positively associated with placental expression of
specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP
concentrations were correlated with the expression of specific placental amino
acid transporters, and thus may be involved in the regulation of amino acid
transfer to the fetus. The positive correlation of VDBP levels and placental
transporter expression suggests that delivery of vitamin D to the placenta may
be important. This exploratory study identifies placental amino acid
transporters which may be altered in response to modifiable maternal factors and
provides a basis for further studies.
Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and postnatal influences. Dentition patterns were recorded at ages 1 and 2 years in 2915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages 1 and 2 years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age 2 years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity.
Despite many advances in recent years for patients with critical paediatric and congenital cardiac disease, significant variation in outcomes remains across hospitals. Collaborative quality improvement has enhanced the quality and value of health care across specialties, partly by determining the reasons for variation and targeting strategies to reduce it. Developing an infrastructure for collaborative quality improvement in paediatric cardiac critical care holds promise for developing benchmarks of quality, to reduce preventable mortality and morbidity, optimise the long-term health of patients with critical congenital cardiovascular disease, and reduce unnecessary resource utilisation in the cardiac intensive care unit environment. The Pediatric Cardiac Critical Care Consortium (PC4) has been modelled after successful collaborative quality improvement initiatives, and is positioned to provide the data platform necessary to realise these objectives. We describe the development of PC4 including the philosophical, organisational, and infrastructural components that will facilitate collaborative quality improvement in paediatric cardiac critical care.
To prepare cholesteric liquid crystalline nonlinear optical materials with ability to be vitrified on cooling and form long time stability cholesteric glasses at room temperature, a series of platinum acetylide complexes modified with cholesterol has been synthesized. The materials synthesized have the formula trans-Pt(PR3)(cholesterol (3 or 4)-ethynyl benzoate)(1-ethynyl-4-X-benzene), where R = Et, Bu or Oct and X = H, F, OCH3 and CN. A cholesteric liquid crystal phase was observed in the complexes R = Et, and X = F, OCH3 and CN but not in any of the other complexes. When X = CN, a cholesteric glass was observed at room temperature which remained stable up to 130 °C, then converted to a mixed crystalline/cholesteric phase and completely melted to an isotropic phase at 230 °C. When X = F or OCH3 the complexes were crystalline at room temperature with conversion to the cholesteric phase upon heating to 190 and 230 °C, respectively. In the series X = CN, OCH3 and F, the cholesteric pitch was determined to be 1.7, 3.4 and 9.0 µ, respectively.