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Clonal Mycobacterium mucogenicum isolates (determined by molecular typing) were recovered from 19 bronchoscopic specimens from 15 patients. None of these patients had evidence of mycobacterial infection. Laboratory culture materials and bronchoscopes were negative for Mycobacteria. This pseudo-outbreak was caused by contaminated ice used to provide bronchoscopic lavage. Control was achieved by transitioning to sterile ice.
The aim of this study was to explore the experiences of radiotherapy students on clinical placement, specifically focussing on the provision of well-being support from clinical supervisors.
Materials and methods:
Twenty-five students from the University of the West of England and City University of London completed an online evaluation survey relating to their experiences of placement, involving Likert scales and open-ended questions.
The quantitative results were generally positive; however, the qualitative findings were mixed. Three themes emerged: (1) provision of information and advice; (2) an open, inclusive and supportive working environment; and (3) a lack of communication, understanding, and consistency.
Students’ experiences on placement differed greatly and appeared to relate to their specific interactions with different members of staff. It is suggested that additional training around providing well-being support to students may be of benefit to clinical supervisors.
Despite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: −70.67, 95% CI −101.90 to −39.43, P<0.001), 16% (RR: 0.84, 95% CI 0.73–0.98, P=0.026) and 19% (RR: 0.81, 95% CI 0.69–0.96, P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD −98.80, 95% CI −178.85 to −18.76, P=0.016) and 65% (RR: 0.35, 95% CI 0.17–0.72, P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26–0.92, P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: −210.93, 95% CI −374.77 to −46.71, P=0.012 and WMD:−295.93, 95% CI −501.76 to −90.10, P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.
Molecular characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases remains unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 cases (81% of the cohort). The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)) or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3AK27M (2%) or IDH1R132H (0.5%) mutations, as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of KIAA1549-BRAF fused patients compared to BRAFV600E with 10-year OS 97.7% (95%, CI 95.5-100) and 83.9% (95%, CI 72.5-95.6), respectively. In addition to survival, molecular alterations predicted differences in response to conventional therapeutics; BRAF fused patients showed a 46% response-rate, versus only 14% in V600E patients. pLGGs harboring H3F3AK27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.
Silicified beyrichiocopid and podocopid ostracods from limestone nodules derived from the middle part of the Ichinotani Formation within the Hida Gaien Terrane of central Honshu Island, Japan, are associated with fusulinid foraminifera that indicate strata of the middle Moscovian (Pennsylvanian, Carboniferous). This is a rare record of ostracods from the Palaeozoic of Japan and the first systematic description of ostracods from the Carboniferous of the Hida Gaien Terrane. The fauna comprises six ostracod species (two new) assigned to the genera Amphissites, Kirkbya, Bairdia, Aechmina and Healdia, and additional material of possible cavellinids. The numerical dominance of ornamented beyrichiocopids such as Kirkbya and Amphissites, along with smaller numbers of smooth podocopids such as Bairdia, indicates an ‘Eifelian mega-assemblage’ ecotype (sensu G. Becker), that is typical of mid Palaeozoic shallow marine, high-energy environments in a fore-reef ecosystem.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Takotsubo cardiomyopathy has been associated with the use of catecholamines; however, its development after the use of nebulised adrenaline for the management of acute airway obstruction has not previously been described.
A 66-year-old man with squamous cell carcinoma of the larynx, with tumour–node–metastasis staging of T3N2cM0, confirmed by biopsy and computed tomography, presented to the emergency department with acute airway obstruction. He was treated twice with nebulised adrenaline and intravenous dexamethasone. After a period of 24 hours, cardiac rhythm changes were noted on telemetry. A 12-lead electrocardiogram showed widespread T-wave inversion and QT prolongation suggestive of an acute coronary syndrome. Coronary angiography demonstrated no coronary artery disease, but left ventricular angiography showed marked apical ballooning and apical wall akinesia consistent with a diagnosis of takotsubo cardiomyopathy.
Takotsubo cardiomyopathy can mimic true ischaemic heart disease and the diagnosis requires a high index of suspicion in patients managed with nebulised adrenaline.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
A community outbreak of legionellosis occurred in Barrow-in-Furness, Cumbria, during July and August 2002. A descriptive study and active case-finding were instigated and all known wet cooling systems and other potential sources were investigated. Genotypic and phenotypic analysis, and amplified fragment length polymorphism of clinical human and environmental isolates confirmed the air-conditioning unit of a council-owned arts and leisure centre to be the source of infection. Subsequent sequence-based typing confirmed this link. One hundred and seventy-nine cases, including seven deaths [case fatality rate (CFR) 3·9%] were attributed to the outbreak. Timely recognition and management of the incident very likely led to the low CFR compared to other outbreaks. The outbreak highlights the responsibility associated with managing an aerosol-producing system, with the potential to expose and infect a large proportion of the local population and the consequent legal ramifications and human cost.
Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCCmec, and Panton–Valentine leukocidin (PVL), representing 106 community-onset infections; 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to <3 non-β-lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26–61] and 15% of MSSA (95% CI 8–28). PVL was associated with infections of the trunk, head or neck (56·4% vs. 24·3%, P = 0·005) in younger patients (23 vs. 52 years, P < 0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9–26·2), suggesting underlying differences in exposure and/or pathogenesis.
Thirty pyrite samples from a wide range of localities were analysed using relative comparator and k0 neutron activation analysis (NAA) techniques at the University of Missouri Research Reactor, Columbia, Missouri, USA (MURR) and the Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia (ANSTO), respectively. Statistical analyses of the trace-element data produced by the two methods showed a generally good correlation, with the majority of elemental concentrations of paired data reported by MURR and ANSTO being indistinguishable at a 0.05 significance level. Trace-element analyses of pyrite from Navajún in Spain by both techniques compare well with published data. There is evidence for contamination by Al, Na and Ti in one set of samples, this is likely to have been introduced by contact with a plastic used in sample preparation.
The long-chain n-3 PUFA, EPA, is believed to be important for skin health, including roles in the modulation of inflammation and protection from photodamage. FFQ and blood levels are used as non-invasive proxies for assessing skin PUFA levels, but studies examining how well these proxies reflect target organ content are lacking. In seventy-eight healthy women (mean age 42·8, range 21–60 years) residing in Greater Manchester, we performed a quantitative analysis of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n 39). Linear associations between the three n-3 PUFA measurements were assessed by Spearman correlation coefficients and agreement between these measurements was estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA and DHA was 171 (sd 168) and 236 (sd 248) mg/d, respectively. EPA showed significant correlations between FFQ assessments and both erythrocyte (r 0·57, P< 0·0001) and dermal (r 0·33, P= 0·05) levels, as well as between erythrocytes and dermis (r 0·45, P= 0·008). FFQ intake of DHA and the sum of n-3 PUFA also correlated well with erythrocyte concentrations (r 0·50, P< 0·0001; r 0·27, P= 0·03). Agreement between ranked thirds of dietary intake, blood and dermis approached 50 % for EPA and DHA, though gross misclassification was lower for EPA. Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA, EPA, may be utilised as well-correlated measures of its dermal bioavailability.
Insurance accounting has for many years proved a challenging topic for standard setters, preparers and users, often described as a “black box”. Will recent developments, in particular the July 2010 Insurance Contracts Exposure Draft, herald a new era?
This paper reviews these developments, setting out key issues and implications. It concentrates on issues relevant to life insurers, although much of the content is also relevant to non-life insurers.
The paper compares certain IFRS and Solvency II developments, recognising that UK insurers face challenges in implementing new financial and regulatory reporting requirements in similar timeframes. The paper considers resulting external disclosure requirements and a possible future role for supplementary information.
Participants with mild cognitive impairment (MCI) have a higher likelihood of developing Alzheimer's disease (AD) compared to those without MCI, and functional magnetic resonance neuroimaging (fMRI) used with MCI participants may prove to be an important tool in identifying early biomarkers for AD. We tested the hypothesis that functional connectivity differences exist between older adults with and without MCI using resting-state fMRI. Data were collected on over 200 participants of the Rush Memory and Aging Project, a community-based, clinical-pathological cohort study of aging. From the cohort, 40 participants were identified as having MCI, and were compared to 40 demographically matched participants without cognitive impairment. MCI participants showed lesser functional connectivity between the posterior cingulate cortex and right and left orbital frontal, right middle frontal, left putamen, right caudate, left superior temporal, and right posterior cingulate regions; and greater connectivity with right inferior frontal, left fusiform, left rectal, and left precentral regions. Furthermore, in an alternate sample of 113, connectivity values in regions of difference correlated with episodic memory and processing speed. Results suggest functional connectivity values in regions of difference are associated with cognitive function and may reflect the presence of AD pathology and increased risk of developing clinical AD. (JINS, 2012, 18, 39–48)