Herschel observations of EXtraordinary Sources: Analysis of the full Herschel/HIFI molecular line survey of Sagittarius B2(N)

A sensitive broadband molecular line survey of the Sagittarius B2(N) star-forming region has been obtained with the HIFI instrument on the Herschel Space Observatory, offering the first high-spectral resolution look at this well-studied source in a wavelength region largely inaccessible from the ground (625-157 um). From the roughly 8,000 spectral features in the survey, a total of 72 isotopologues arising from 44 different molecules have been identified, ranging from light hydrides to complex organics, and arising from a variety of environments from cold and diffuse to hot and dense gas. We present an LTE model to the spectral signatures of each molecule, constraining the source sizes for hot core species with complementary SMA interferometric observations, and assuming that molecules with related functional group composition are cospatial. For each molecule, a single model is given to fit all of the emission and absorption features of that species across the entire 480-1910 GHz spectral range, accounting for multiple temperature and velocity components when needed to describe the spectrum. As with other HIFI surveys toward massive star forming regions, methanol is found to contribute more integrated line intensity to the spectrum than any other species. We discuss the molecular abundances derived for the hot core, where the local thermodynamic equilibrium approximation is generally found to describe the spectrum well, in comparison to abundances derived for the same molecules in the Orion KL region from a similar HIFI survey.Comment: Accepted to ApJ. 64 pages, 14 figures. Truncated abstrac

Developing health science students into integrated health professionals: a practical tool for learning

BACKGROUND:An integrated sense of professionalism enables health professionals to draw on relevant knowledge in context and to apply a set of professional responsibilities and ethical principles in the midst of changing work environments 12. Inculcating professionalism is therefore a critical goal of health professional education. Two multi-professional courses for first year Health Science students at the University of Cape Town, South Africa aim to lay the foundation for becoming an integrated health professional 3. In these courses a diagram depicting the domains of the integrated health professional is used to focus the content of small group experiential exercises towards an appreciation of professionalism. The diagram serves as an organising framework for conceptualising an emerging professional identity and for directing learning towards the domains of 'self as professional' 45.OBJECTIVE:This paper describes how a diagrammatic representation of the core elements of an integrated health professional is used as a template for framing course content and for organising student learning. Based on the assumption that all health care professionals should be knowledgeable, empathic and reflective, the diagram provides students and educators with a visual tool for investigating the subjective and objective dimensions of professionalism. The use of the diagram as an integrating point of reference for individual and small group learning is described and substantiated with relevant literature. CONCLUSION: The authors have applied the diagram with positive impact for the past six years with students and educators reporting that "it just makes sense". The article includes plans for formal evaluation. Evaluation to date is based on preliminary, informal feedback on the value of the diagram as a tool for capturing the domains of professionalism at an early stage in the undergraduate education of health professional students

Talk to the Virtual Hands: Self-Animated Avatars Improve Communication in Head-Mounted Display Virtual Environments

Background When we talk to one another face-to-face, body gestures accompany our speech. Motion tracking technology enables us to include body gestures in avatar-mediated communication, by mapping one's movements onto one's own 3D avatar in real time, so the avatar is self-animated. We conducted two experiments to investigate (a) whether head-mounted display virtual reality is useful for researching the influence of body gestures in communication; and (b) whether body gestures are used to help in communicating the meaning of a word. Participants worked in pairs and played a communication game, where one person had to describe the meanings of words to the other. Principal Findings In experiment 1, participants used significantly more hand gestures and successfully described significantly more words when nonverbal communication was available to both participants (i.e. both describing and guessing avatars were self-animated, compared with both avatars in a static neutral pose). Participants ‘passed’ (gave up describing) significantly more words when they were talking to a static avatar (no nonverbal feedback available). In experiment 2, participants' performance was significantly worse when they were talking to an avatar with a prerecorded listening animation, compared with an avatar animated by their partners' real movements. In both experiments participants used significantly more hand gestures when they played the game in the real world. Conclusions Taken together, the studies show how (a) virtual reality can be used to systematically study the influence of body gestures; (b) it is important that nonverbal communication is bidirectional (real nonverbal feedback in addition to nonverbal communication from the describing participant); and (c) there are differences in the amount of body gestures that participants use with and without the head-mounted display, and we discuss possible explanations for this and ideas for future investigation

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment

Apoptosis of VSMCs (vascular smooth-muscle cells) leads to features of atherosclerotic plaque instability. We have demonstrated previously that plaque-derived VSMCs have reduced IGF1 (insulin-like growth factor 1) signalling, resulting from a decrease in the expression of IGF1R (IGF1 receptor) compared with normal aortic VSMCs [Patel, Zhang, Siddle, Soos, Goddard, Weissberg and Bennett (2001) Circ. Res. 88, 895–902]. In the present study, we show that apoptosis induced by oxidative stress is inhibited by ectopic expression of IGF1R. Oxidative stress repressed IGF1R expression at multiple levels, and this was also blocked by mutant p53. Oxidative stress also induced p53 phosphorylation and apoptosis in VSMCs. p53 negatively regulated IGF1R promoter activity and expression and, consistent with this, p53−/− VSMCs demonstrated increased IGF1R expression, both in vitro and in advanced atherosclerotic plaques in vivo. Oxidative-stress-induced interaction of endogenous p53 with TBP (TATA-box-binding protein) was dependent on p53 phosphorylation. Oxidative stress also increased the association of p53 with HDAC1 (histone deacetylase 1). Trichostatin A, a specific HDAC inhibitor, or p300 overexpression relieved the repression of IGF1R following oxidative stress. Furthermore, acetylated histone-4 association with the IGF1R promoter was reduced in cells subjected to oxidative stress. These results suggest that oxidative-stress-induced repression of IGF1R is mediated by the association of phosphorylated p53 with the IGF1R promoter via TBP, and by the subsequent recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF1R promoter–TBP–p53 complex

On the Conventionalization of Mouth Actions in Australian Sign Language

This study investigates the conventionalization of mouth actions in Australian Sign Language. Signed languages were once thought of as simply manual languages because the hands produce the signs which individually and in groups are the symbolic units most easily equated with the words, phrases and clauses of spoken languages. However, it has long been acknowledged that non-manual activity, such as movements of the body, head and the face play a very important role. In this context, mouth actions that occur while communicating in signed languages have posed a number of questions for linguists: are the silent mouthings of spoken language words simply borrowings from the respective majority community spoken language(s)? Are those mouth actions that are not silent mouthings of spoken words conventionalized linguistic units proper to each signed language, culturally linked semi-conventional gestural units shared by signers with members of the majority speaking community, or even gestures and expressions common to all humans? We use a corpus-based approach to gather evidence of the extent of the use of mouth actions in naturalistic Australian Sign Language–making comparisons with other signed languages where data is available–and the form/meaning pairings that these mouth actions instantiate.40 page(s

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population.

ObjectivesGenome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping.Materials and methodsWe genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p&lt;1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2.Results and conclusionIn the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans