The JCMT Legacy Survey of the Gould Belt: Mapping 13CO and C 18O in Orion A

The Gould Belt Legacy Survey will map star-forming regions within 500 pc, using Heterodyne Array Receiver Programme (HARP), Submillimetre Common-User Bolometer Array 2 (SCUBA-2) and Polarimeter 2 (POL-2) on the James Clerk Maxwell Telescope (JCMT). This paper describes HARP observations of the J= 3 → 2 transitions of 13CO and C18O towards Orion A. The 15 arcsec resolution observations cover 5 pc of the Orion filament, including OMC 1 (including BN–KL and Orion bar), OMC 2/3 and OMC 4, and allow a comparative study of the molecular gas properties throughout the star-forming cloud. The filament shows a velocity gradient of ∼1 km s−1 pc−1 between OMC 1, 2 and 3, and high-velocity emission is detected in both isotopologues. The Orion Nebula and Bar have the largest masses and linewidths, and dominate the mass and energetics of the high-velocity material. Compact, spatially resolved emission from CH3CN, 13CH3OH, SO, HCOOCH3, CH3CHO and CH3OCHO is detected towards the Orion Hot Core. The cloud is warm, with a median excitation temperature of ∼24 K; the Orion Bar has the highest excitation temperature gas, at >80 K. The C18O excitation temperature correlates well with the dust temperature (to within 40 per cent). The C18O emission is optically thin, and the 13CO emission is marginally optically thick; despite its high mass, OMC 1 shows the lowest opacities. A virial analysis indicates that Orion A is too massive for thermal or turbulent support, but is consistent with a model of a filamentary cloud that is threaded by helical magnetic fields. The variation of physical conditions across the cloud is reflected in the physical characteristics of the dust cores. We find similar core properties between starless and protostellar cores, but variations in core properties with position in the filament. The OMC 1 cores have the highest velocity dispersions and masses, followed by OMC 2/3 and OMC 4. The differing fragmentation of these cores may explain why OMC 1 has formed clusters of high-mass stars, whereas OMC 4 produces fewer, predominantly low-mass stars

Medicine and psychiatry in Western culture: Ancient Greek myths and modern prejudices

The origins of Western culture extensively relate to Ancient Greek culture. While many ancient cultures have contributed to our current knowledge about medicine and the origins of psychiatry, the Ancient Greeks were among the best observers of feelings and moods patients expressed towards medicine and toward what today is referred to as 'psychopathology'. Myths and religious references were used to explain what was otherwise impossible to understand or be easily communicated. Most ancient myths focus on ambiguous feelings patients may have had towards drugs, especially psychotropic ones. Interestingly, such prejudices are common even today

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial

BACKGROUND: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. METHODS: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. FINDINGS: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12–52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1–5·1) for TARGIT versus 1·3% (0·7–2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1–4·2) versus 1·1% (0·5–2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0–9·7] vs EBRT 1·7% [0·6–4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5–4·3] for TARGIT vs 1·9% [1·1–3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8–2·5] vs 3·5% [2·3–5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7–5·8) for TARGIT versus 5·3% (3·9–7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029). INTERPRETATION: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research

Notch Signaling Activates Yorkie Non-Cell Autonomously in Drosophila

In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which neoplastic tumor cells generate a supportive microenvironment for tumor growth

The Nature of Knowledge in Composition and Literary Understanding: The Question of Specificity

↵PETER SMAGORINSKY is Assistant Professor, College of Education, University of Oklahoma, 820 Van Vleet Oval, Norman, OK 73019-0. He specializes in classroom literacy.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale - particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone- based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high- resolution sequence map of human structural variation - a standard for genotyping platforms and a prelude to future individual genome sequencing projects