Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver gene

How much do delayed health care seeking, delayed care provision and diversion from primary care contribute to the transmission of STIs

Objectives: To explore the changing pattern of condom use from 1990 to 2000; to identify sociodemographic and behavioural factors associated with condom use; and reasons for condom use in 2000. Methods: Large probability sample surveys administered among those resident in Britain aged 16–44 (n = 13 765 in 1990, n = 11 161 in 2000). Face to face interviews with self completion components collected sociodemographic, behavioural, and attitudinal data. Results: Condom use in the past year among sexually active 16–24 year old men increased from 61.0% in 1990 to 82.1% in 2000 (p<0.0001), and from 42.0% to 63.2% (p<0.0001) among women of the same age, with smaller increases among older age groups. Among individuals reporting at least two partners in the previous 4 week period, approximately two thirds reported inconsistent or no condom use (63.1% (95% CI 55.9% to 69.8%) of the men and 68.5% (95% CI 57.6% to 77.7%) of the women). Conclusions: Rates of condom use increased substantially between 1990 and 2000, particularly among young people. However, inconsistent condom use by individuals with high rates of partner acquisition may contribute significantly to the recent resurgence in STIs. This group is an important target for intensive and specific sexual health interventions

The Extrasolar Planet epsilon Eridani b - Orbit and Mass

Hubble Space Telescope observations of the nearby (3.22 pc), K2 V star epsilon Eridani have been combined with ground-based astrometric and radial velocity data to determine the mass of its known companion. We model the astrometric and radial velocity measurements simultaneously to obtain the parallax, proper motion, perturbation period, perturbation inclination, and perturbation size. Because of the long period of the companion, \eps b, we extend our astrometric coverage to a total of 14.94 years (including the three year span of the \HST data) by including lower-precision ground-based astrometry from the Allegheny Multichannel Astrometric Photometer. Radial velocities now span 1980.8 -- 2006.3. We obtain a perturbation period, P = 6.85 +/- 0.03 yr, semi-major axis, alpha =1.88 +/- 0.20 mas, and inclination i = 30.1 +/- 3.8 degrees. This inclination is consistent with a previously measured dust disk inclination, suggesting coplanarity. Assuming a primary mass M_* = 0.83 M_{\sun}, we obtain a companion mass M = 1.55 +/- 0.24 M_{Jup}. Given the relatively young age of epsilon Eri (~800 Myr), this accurate exoplanet mass and orbit can usefully inform future direct imaging attempts. We predict the next periastron at 2007.3 with a total separation, rho = 0.3 arcsec at position angle, p.a. = -27 degrees. Orbit orientation and geometry dictate that epsilon Eri b will appear brightest in reflected light very nearly at periastron. Radial velocities spanning over 25 years indicate an acceleration consistent with a Jupiter-mass object with a period in excess of 50 years, possibly responsible for one feature of the dust morphology, the inner cavity

1936: Abilene Christian College Bible Lectures - Full Text

Delivered in the auditorium of Abilene Christian College, Abilene, Texas, February 193

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery

ACKNOWLEDGEMENTS Review and editing: S.R. Brown, Professor of Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. Email [email protected]. Patient summary: R.G. Arnott, Retired Professor, Patient Liaison Group, Association of Coloproctology of Great Britain and Ireland, Royal College of Surgeons of England, London, UK. Email [email protected]. Delphi review: C.P. Macklin. BMedSci BM BS FRCS DM, Consultant Colorectal Surgeon, Mid Yorkshire Hospitals, UK. Email [email protected] reviewedPublisher PD

1968: Abilene Christian College Bible Lectures - Full Text

CROWNING FIFTY YEARS” Being the Fiftieth Annual ABILENE CHRISTIAN COLLEGE BIBLE LECTURES - 1968 J. D. THOMAS, LECTURESHIP DIRECTOR, EDITOR Published by ABILENE CHRISTIAN COLLEGE ACC Station, Abilene, Texas 7960

Thermochronology of the modern Indus River bedload: New insight into the controls on the marine stratigraphic record

The Indus River is the only major drainage in the western Himalaya and delivers a long geological record of continental erosion to the Arabian Sea, which may be deciphered and used to reconstruct orogenic growth if the modern bedload can be related to the mountains. In this study we collected thermochronologic data from river sediment collected near the modern delta. U-Pb ages of zircons spanning 3 Gyr show that only ∼5% of the eroding crust has been generated since India-Asia collision. The Greater Himalaya are the major source of zircons, with additional contributions from the Karakoram and Lesser Himalaya. The 39Ar/40Ar dating of muscovites gives ages that cluster between 10 and 25 Ma, differing from those recorded in the Bengal Fan. Biotite ages are generally younger, ranging 0–15 Ma. Modern average exhumation rates are estimated at ∼0.6 km/m.y. or less, and have slowed progressively since the early Miocene (∼20 Ma), although fission track (FT) dating of apatites may indicate a recent moderate acceleration in rates since the Pliocene (∼1.0 km/m.y.) driven by climate change. The 39Ar/40Ar and FT techniques emphasize the dominance of high topography in controlling the erosional flux to the ocean. Localized regions of tectonically driven, very rapid exhumation (e.g., Nanga Parbat, S. Karakoram metamorphic domes) do not dominate the erosional record

1954: Abilene Christian College Bible Lectures - Full Text

Preface The 1954 Abilene Christian College Lectureship was one of the best attended and most successful in the history of the school. Considerable interest was manifested in the timely theme, “Overcoming Dangerous Tendencies,” and in the two special topics, “Ways and Means of Doing Mission Work,” and “Caring For Widows and Orphans.” The reports from the mission fields were highly stimulating, and all in all, the speeches were unusually high caliber. The Panel Discussions were also on timely subjects and well presented. They received a warm response, as did also the thirty classes that were conducted each day. These classes were taught by persons expert in their particular fields, and covered a wide range of interests to the faithful, working Christian. We at Abilene Christian College predict for this book of Lectures a wide and hearty reception, and believe that its reading will issue in profit to the individual and to the church at large. J. D. Thomas Lectureship Directo

1962: Abilene Christian College Bible Lectures - Full Text

THE RESTORATION PRINCIPLE” Being the Abilene Christian College Annual Bible Lectures 1962 Price: $3.95 Published by ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE ACC Station Abilene, Texa

Genotype-phenotype characterisation of long survivors with motor neuron disease in Scotland

Background: We investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication. Methods: Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as &gt; 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls. Results: 58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions. Conclusions: Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication