Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high <sup>3</sup>He/<sup>4</sup>He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic <sup>3</sup>He/<sup>4</sup>He ratios yet recorded. A strong correlation between <sup>3</sup>He/<sup>4</sup>He and <sup>87</sup>Sr/<sup>86</sup>Sr, <sup>143</sup>Nd/<sup>144</sup>Nd and trace element ratios demonstrate that the <sup>3</sup>He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest <sup>3</sup>He/<sup>4</sup>He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a <sup>3</sup>He-recharged depleted mantle (HRDM) reservoir may be the principal source of high <sup>3</sup>He/<sup>4</sup>He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT):a mixed methods, open-label, pragmatic randomised trial

Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness.In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589.Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group vs 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group).There was no significant difference between ciclosporin and infliximab in clinical effectiveness.NIHR Health Technology Assessment programme

The relationship between workers' self-reported changes in health and their attitudes towards a workplace intervention: lessons from smoke-free legislation across the UK hospitality industry

Background: The evaluation of smoke-free legislation (SFL) in the UK examined the impacts on exposure to second-hand smoke, workers’ attitudes and changes in respiratory health. Studies that investigate changes in the health of groups of people often use self-reported symptoms. Due to the subjective nature it is of interest to determine whether workers’ attitudes towards the change in their working conditions may be linked to the change in health they report. Methods: Bar workers were recruited before the introduction of the SFL in Scotland and England with the aim of investigating their changes to health, attitudes and exposure as a result of the SFL. They were asked about their attitudes towards SFL and the presence of respiratory and sensory symptoms both before SFL and one year later. Here we examine the possibility of a relationship between initial attitudes and changes in reported symptoms, through the use of regression analyses. Results: There was no difference in the initial attitudes towards SFL between those working in Scotland and England. Bar workers who were educated to a higher level tended to be more positive towards SFL. Attitude towards SFL was not found to be related to change in reported symptoms for bar workers in England (Respiratory, p = 0.755; Sensory, p = 0.910). In Scotland there was suggestion of a relationship with reporting of respiratory symptoms (p = 0.042), where those who were initially more negative to SFL experienced a greater improvement in self-reported health. Conclusions: There was no evidence that workers who were more positive towards SFL reported greater improvements in respiratory and sensory symptoms. This may not be the case in all interventions and we recommend examining subjects’ attitudes towards the proposed intervention when evaluating possible health benefits using self-reported methods. Keywords: ‘Self-Reported Health’, Attitudes, ‘Workplace Intervention’, ‘Public Health Intervention

A review of the systematic biology of fossil and living bony-tongue fishes, Osteoglossomorpha (Actinopterygii: Teleostei)

The bony-tongue fishes, Osteoglossomorpha, have been the focus of a great deal of morphological, systematic, and evolutionary study, due in part to their basal position among extant teleostean fishes. This group includes the mooneyes (Hiodontidae), knifefishes (Notopteridae), the abu (Gymnarchidae), elephantfishes (Mormyridae), arawanas and pirarucu (Osteoglossidae), and the African butterfly fish (Pantodontidae). This morphologically heterogeneous group also has a long and diverse fossil record, including taxa from all continents and both freshwater and marine deposits. The phylogenetic relationships among most extant osteoglossomorph families are widely agreed upon. However, there is still much to discover about the systematic biology of these fishes, particularly with regard to the phylogenetic affinities of several fossil taxa, within Mormyridae, and the position of Pantodon. In this paper we review the state of knowledge for osteoglossomorph fishes. We first provide an overview of the diversity of Osteoglossomorpha, and then discuss studies of the phylogeny of Osteoglossomorpha from both morphological and molecular perspectives, as well as biogeographic analyses of the group. Finally, we offer our perspectives on future needs for research on the systematic biology of Osteoglossomorpha

Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer

INTRODUCTION: BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown to occur in sporadic breast tumours and to be associated with reduced gene expression. We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype. METHODS: Primary sporadic breast tumours were analysed for BRCA1α promoter methylation by methylation specific PCR and for allelic imbalance (AI) at BRCA1 and BRCA2 loci by microsatellite analysis and TP53 (also known as p53) mutations by constant denaturing gel electrophoresis. The BRCA1 methylated tumours were analysed for BRCA1 copy alterations by fluorescence in situ hybridisation and BRCA1 expression by immunostaining. RESULTS: BRCA1 methylation was found in 13/143 (9.1%) sporadic breast tumours. The BRCA1 methylated tumours were significantly associated with estrogen receptor (ER) negativity (P = 0.0475) and displayed a trend for BRCA1 AI (P = 0.0731) as well as young-age at diagnosis (≤ 55; P = 0.0898). BRCA1 methylation was not associated with BRCA2 AI (P = 0.5420), although a significant association was found between BRCA1 AI and BRCA2 AI (P < 0.0001). Absent/markedly reduced BRCA1 expression was observed in 9/13 BRCA1 methylated tumours, most of which had BRCA1 deletion. An elevated TP53 mutation frequency was found among BRCA1 methylated tumours (38.5%) compared with non-methylated tumours (17.2%). The BRCA1 methylated tumours were mainly of tumour grade 3 (7/13) and infiltrating ductal type (12/13). Only one methylated tumour was of grade 1. CONCLUSION: BRCA1 methylation is frequent in primary sporadic breast tumours. We found an indication for BRCA1 methylation to be associated with AI at the BRCA1 locus. Almost all BRCA1 methylated tumours with absent/markedly reduced BRCA1 expression (8/9) displayed BRCA1 deletion. Thus, epigenetic silencing and deletion of the BRCA1 gene might serve as Knudson's two 'hits' in sporadic breast tumorigenesis. We observed phenotypic similarities between BRCA1 methylated and familial BRCA1 tumours, based on BRCA1 deletion, TP53 mutations, ER status, young age at diagnosis and tumour grade

Bilateral multifocal Warthin's tumors in upper neck lymph nodes. report of a case and brief review of the literature

Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the parotid gland. Due to their benign clinical behavior, the low rates of recurrence and malignant transformation they were classified as tumor-like lesions. In addition, a polyclonal growth of the epithelial components of the tumor could be detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal appearance is extremely rare. Even if the pathogenesis is still unclear a heterotopia of salivary tissue during embryogenesis is the most likely explanation for the origin of these tumors in the upper neck and periparotideal region. Here we present a rare case of bilateral, multifocal, extraglandular Warthin's tumors in lymph nodes of the upper neck and give a brief review of the literature. If a primary malignancy can be excluded by a careful staging procedure prior to the operation an isolated excision of the lesions of the neck is the adequate treatment

Dyspraxia and autistic traits in adults with and without autism spectrum conditions

BACKGROUND: Autism spectrum conditions (ASC) are frequently associated with motor coordination difficulties. However, no studies have explored the prevalence of dyspraxia in a large sample of individuals with and without ASC or associations between dyspraxia and autistic traits in these individuals. METHODS: Two thousand eight hundred seventy-one adults (with ASC) and 10,706 controls (without ASC) self-reported whether they have been diagnosed with dyspraxia. A subsample of participants then completed the Autism Spectrum Quotient (AQ; 1237 ASC and 6765 controls) and the Empathy Quotient (EQ; 1147 ASC and 6129 controls) online through the Autism Research Centre website. The prevalence of dyspraxia was compared between those with and without ASC. AQ and EQ scores were compared across the four groups: (1) adults with ASC with dyspraxia, (2) adults with ASC without dyspraxia, (3) controls with dyspraxia, and (4) controls without dyspraxia. RESULTS: Adults with ASC were significantly more likely to report a diagnosis of dyspraxia (6.9%) than those without ASC (0.8%). In the ASC group, those with co-morbid diagnosis of dyspraxia did not have significantly different AQ or EQ scores than those without co-morbid dyspraxia. However, in the control group (without ASC), those with dyspraxia had significantly higher AQ and lower EQ scores than those without dyspraxia. CONCLUSIONS: Dyspraxia is significantly more prevalent in adults with ASC compared to controls, confirming reports that motor coordination difficulties are significantly more common in this group. Interestingly, in the general population, dyspraxia was associated with significantly higher autistic traits and lower empathy. These results suggest that motor coordination skills are important for effective social skills and empathy

Multidimensional chemical control of CRISPR–Cas9

Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions-including dose, time, specificity, and mutually exclusive modulation of multiple genes-are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation

Supervised team management, with or without structured psychotherapy, in heavy users of a mental health service with borderline personality disorder: a two-year follow-up preliminary randomized study

<p>Abstract</p> <p>Background</p> <p>Individuals affected by severe Borderline Personality Disorder (BPD) are often heavy users of Mental Health Services (MHS). Short-term treatments currently used in BPD therapy are useful to target disruptive behaviors but they are less effective in reducing heavy MHS use. Therefore, alternative short-term treatments, less complex than long-term psychodynamic psychotherapies but specifically oriented to BPD core problems, need to be developed to reduce MHS overuse. This study aimed to evaluate the efficacy of adding Sequential Brief Adlerian Psychodynamic Psychotherapy (SB-APP) to Supervised Team Management (STM) in BPD treatment compared to STM alone in a naturalistic group of heavy MHS users with BPD. Effectiveness was evaluated 6 times along a two-year follow-up.</p> <p>Methods</p> <p>Thirty-five outpatients who met inclusion criteria were randomly assigned to two treatment groups (STM = 17; SB-APP = 18) and then compared. Clinical Global Impression (CGI) and CGI-modified (CGI-M) for BPD, Global Assessment of Functioning (GAF), State-Trait Anger Expression Inventory (STAXI), and Symptom Checklist-90 Revised (SCL-90-R) were administered at T1, T3, T6, T12, T18 and T24. At T12 the Working Alliance Inventory-Short Form (WAI-S) was also completed. At the one-year follow-up, SB-APP group did not receive any additional individual psychological support. MHS team was specifically trained in BPD treatment and had regular supervisions.</p> <p>Results</p> <p>All patients improved on CGI, GAF, and STAXI scores after 6 and 12 months, independently of treatment received. SB-APP group showed better outcome on impulsivity, suicide attempts, chronic feelings of emptiness, and disturbed relationships. We found a good stabilization at the one year follow-up, even after the interruption of brief psychotherapy in the SB-APP group.</p> <p>Conclusions</p> <p>Although STM for BPD applied to heavy MHS users was effective in reducing symptoms and improving their global functioning, adding a time-limited and focused psychotherapy was found to achieve a better outcome. In particular, focusing treatment on patients' personality with a specific psychotherapeutic approach (i.e. SB-APP) seemed to be more effective than STM alone.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT1356069">NCT1356069</a></p

cDNA Cloning and Expression Analysis of Gustavus Gene in the Oriental River Prawn Macrobrachium nipponense

The gustavus gene is required for localizing pole plasm and specifying germ cells. Research on gustavus gene expression will advance our understanding of the biological function of gustavus in animals. A cDNA encoding gustavus protein was identified and termed MnGus in the oriental river prawn Macrobrachium nipponense. Bioinformatic analyses showed that this gene encoded a protein of 262 amino acids and the protein belongs to the Spsb1 family. Real-time quantitative PCR analyses revealed that the expression level of MnGus in prawn embryos was slightly higher at the cleavage stage than at the blastula stage, and reached the maximum level during the zoea stage of embryos. The minimum level of MnGus expression occurred during the perinucleolus stage in the ovary, while the maximum was at the oil globule stage, and then the level of MnGus expression gradually decreased with the advancement of ovarian development. The expression level of MnGus in muscle was much higher than that in other tissues in mature prawn. The gustavus cDNA sequence was firstly cloned from the oriental river prawn and the pattern of gene expression was described during oocyte maturation, embryonic development, and in other tissues. The differential expression patterns of MnGus in the embryo, ovary and other somatic tissues suggest that the gustavus gene performs multiple physiological functions in the oriental river prawn