Pro-neural transcription factors as cancer markers

BACKGROUND: The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours.

RESULTS: Expression arrays were used to identify up-regulated transcripts in a neuroendocrine (NE) transgenic mouse model of prostate cancer. Amongst these were several genes normally expressed in neural tissues, including the pro-neural transcription factors Ascl1 and Hes6. Using quantitative RT-PCR and immuno-histochemistry we showed that these same genes were highly expressed in castrate resistant, metastatic LNCaP cell-lines. Finally we performed a meta-analysis on expression array datasets from human clinical material. The expression of these pro-neural transcripts effectively segregates metastatic from localised prostate cancer and benign tissue as well as sub-clustering a variety of other human cancers.

CONCLUSION: By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined. We suggest that the aberrant initiation of differentiation programs may confer a selective advantage on cells in all contexts and this approach to identify biomarkers therefore has the potential to uncover proteins equally applicable to pre-clinical and clinical cancer biology.

The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer

The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression).

PATIENT SUMMARY: This first-in-man study defines the rapid gene expression changes taking place in prostate cancer (PCa) following castration. Expression levels of the genes that the androgen receptor regulates are predictive of treatment outcome. Upregulation of oestrogen receptor 1 is a mechanism by which PCa cells may survive despite castration.

Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial)

Background: Traffic light labelling of foods—a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods—has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions.

Methods/design: The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial.

Discussion: The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be generalised to a wider population if shown to be feasible in the main trial.

Conspicuous by their abstinence: the limited engagement of heroin users in English and Welsh Drug Recovery Wings

Background In recent years, an abstinence-focused, ‘recovery’ agenda has emerged in UK drug policy, largely in response to the perception that many opioid users had been ‘parked indefinitely’ on Opioid Substitution Therapy (OST). The introduction of ten pilot ‘Drug Recovery Wings’ (DRWs) in 2011 represents the application of this recovery agenda to prisons. This paper describes the DRWs’ operational models, the place of opiate dependent prisoners within them, and the challenges of delivering ‘recovery’ in prison. Methods In 2013, the implementation and operational models of all ten pilot DRWs were rapidly assessed. Up to three days were spent in each DRW, undertaking semi-structured interviews with a sample of 94 DRW staff and 102 DRW residents. Interviews were fully transcribed, and coded using grounded theory. Findings from the nine adult prisons are presented here. Results Four types of DRW were identified, distinguished by their size and selection criteria. Strikingly, no mid- or large-sized units regularly supported OST recipients through detoxification. Type A were large units whose residents were mostly on OST with long criminal records and few social or personal resources. Detoxification was rare, and medication reduction slow. Type B's mid-sized DRW was developed as a psychosocial support service for OST clients seeking detoxification. However, staff struggled to find such prisoners, and detoxification again proved rare. Type C DRWs focused on abstinence from all drugs, including OST. Though OST clients were not intentionally excluded, very few applied to these wings. Only Type D DRWs, offering intensive treatment on very small wings, regularly recruited OST recipients into abstinence-focused interventions. Conclusion Prison units wishing to support OST recipients in making greater progress towards abstinence may need to be small, intensive and take a stepped approach based on preparatory motivational work and extensive preparation for release. However, concerns about post-release deaths will remain.

Short films about flying

Online artwork which streams web-cam images live from the Internet and re-mixes them into disjointed narrative sequences, thereby producing cinema as a 'found object' made entirely of live material streamed from the internet. ‘Short Films about Flying’ is an online film which explores how a cinematic work can be generated using live material from the internet. The work is driven by software that takes surveillance video from a live camera feed at Logan Airport, Boston, and combines this with randomly grabbed audio from the web and texts taken from websites, chat rooms, message boards etc. This results in an endless open edition of unique cinematic works in real-time. By combining the language of cinema with global real-time data technologies, this work is one of the first new media artworks to re-imagine the internet in a different sensory form as a cinematic space. ‘Short Films about Flying’ was developed over the course of a year in collaboration with Jon Thomson (Slade) to explore how the concept of the found object can be re-conceptualised as the found data stream. It has informed other research by Craighead and Thomson, such as the web project http://www.templatecinema.com, and began an examination into relationships between montage and live virtual data –an early example of which would be ‘Flat Earth’, an animated work developed for Channel 4 in 2007, with the production company Animate. This piece has been cited in discussions on new media art, as a significant example of artworks using a database as their determining structure. It was acquired for the Arts Council Collection and has continuously toured significant international venues over the last 4 years. Citations include:’ Time and Technology’ by Charlie Gere (2006); 'The Wrong Categories' by Kris Cohen (2006); 'Networked Art - Practices and Positions' edited by Tom Corby (Routledge 2005) and Grayson Perry in The Times (9.8.06).

The battle of Cable Street

This witness seminar on the events in the East End of London of 4 October 1936, traditionally known as the ‘Battle of Cable Street’, was held at the Institute of Historical Research on 1 May 1991. It was chaired by Professor Geoffrey Alderman and introduced by Noreen Branson. The participants were Sid Bailey (former member of the BUF), Dr David Cesarani, Tony Gilbert, Charlie Goodman, Joyce Goodman, Professor Colin Holmes, Frank Lesser, Kevin Morgan (biographer of Harry Pollitt), Phil Piratin (Communist MP for Mile End 1945–50), Michael Quill, Jack Shaw, Harold Smith, Ronald F. Webb (former member of the BUF) and Len Wise (former member of the BUF). Yvonne Kapp was unable to attend but she sent a short account of her recollections of the event and this has been included with this transcript.

Hesperian College football team, Woodland, California, 1891

Hesperian College football team, Woodland, California, 1891. Standing, left to right: Sidney Elston, Ernest Norton, Charlie Elston, Charlie Merritt, Jimmie Johnston, Rolls Bray, Frank Zimmerman. Seated, left to right: John Gardner, Bill Banks, Jerry Rust, Bob Simons. On floor, left to right: Joe Harlan, George Martin.

Charles C. Chapman's birthday celebration, Fullerton, California,1932

Family portrait taken at Charles C. Chapman's birthday celebration, Fullerton, California,July 2, 1932. The group poses outside his residence on the lawn. Top row [left to right]: Arthur Irvin, Charles Wickett, Irvin Chapman, Sam Collins, Paul Williams, Grant Chapman,, Sidney Chapman, Clay McCarn, Earl Chapman's son David McDougal, Earl Chapman's son William McDougal, Earl Chapman, Harry Chapman, William Wickett Sr. Second row [left to right]: Mr. VanMeter, Mrs. Sinclair, C. C. Sinclair, John Franklin, Way Bagley, Marjorie Collins, Emma Williams, Ruth Chapman, Vesta Chapman, Inez Bagley, Grace Chapman, Bertha Chapman, Clough Chapman, Frank and Bertha Chapman's daughter Agnes McDougal [Streech], Georgiana Chapman, Thela Clough, Mrs. Earl [Ann] Chapman, Bessie Reynolds, Fred Chapman, E. B. [Bert] Reynolds. Seated [left to right]: Mrs. VanMeter, Hattie Clark, Louie Messlar, Charlie Thamer, Louella Thamer, Dolla Harris, Stanley Chapman Sr. holding Mary Anne, Ethel Wickett, Charles C. Chapman, Clara Chapman, Colum C. Chapman, Aunt Annie Colum, Deryth Chapman, Anna Marie Chapman, Floy Chapman, Edith Chapman. Front row [left to right]: Sam E. Collins, Bill Wickett Jr., Joyce Chapman, Marilyn Chapman, Elizabeth Chapman, Mary McCarn, Nina Chapman Lescher, Jodeane Collins, Bob Gibb, Jean Chapman. In front is a floral arrangement with drawing of a Western Union telegram "To Chas. C. Chapman, July 2, 1932, N. Fullerton, Cal., 'Wishing you a happy birthday, Nina."

Bell Family Bible, Miscellaneous, 1895 - 1918

A page from the Bell Family Bible entitled "Miscellaneous" recording the dates and places of birth of the children of Charles and Mary Bell. The birth dates for the eight children listed range from 1895 to 1918. There is also a single entry under the heading "Age of Children of Delbert Bell". This Bible was in the possession of the Rick Bell of St. Catharines. The Bell family is descended from former Black slaves from the United States who settled in Canada.The handwritten entries appear to be as follows: "Ages of the children of Charles and Mary Bell are Wilbert Otto Bell born November 7th 1895 Erie Pa. Edna Beatrice Bell born May 25th 1897 Erie Pa. Lewis Terrell Bell born April 8th 1899 St. Catharines Ont. Gertrude Bell born November 26th 1902 St. Catharines Ont. Charles Henry Bell born June 6th 1906 St. Catharines Ont. Richard Wilson Bell born March 19th 1911 William Willoughby Bell born May 2nd 1912 both in St. Catharines Ontario Age of Children of Delbert Bell March 12th 1918 Delbert Charlie Bell"

Merritton Pen Centre Lions photographs, 1960.

Two black and white photographs of the Merritton Pen Centre Lions, dated 1960. One photograph is of the team, and the other one is of the pitching staff. The photograph of the team includes Bill Colbey (Lions Club), Jack McFadden, Bob Sunderland, Gary Blank, John MacDonald, John Davis (Coach), John Dempsey, Art Barclay, Frank Krsul, Percy Gilligan (Pen Centre), Terry Saxton, George Krusl, Dave Morris, Ian MacDonald (Mgr), Pete Holowchuk, Bernie Stubbert, Bill Hicks, Jim Thomson (Bat Boy), George Depitris (Property) and Charlie McGuire. Jim Hale is absent. The photograph of the pitching staff includes John Dempsey, Art Barclay and John MacDonald.

Description des pratiques vaccinales d’infirmières en situation de refus parental avant et après une formation interactive

Malgré les succès spectaculaires de l’immunisation comme mesure de santé publique, certains parents continuent de refuser de vacciner leurs enfants (Diekema, 2005). C’est pourquoi qu’au cours des dernières décennies, des éclosions de maladies évitables par la vaccination comme la rougeole et la coqueluche ont été observées au Canada, surtout chez la population non vaccinée (Hinman, 2000). Au Québec, depuis l’entrée en vigueur de la loi 90 en 2003, les infirmières peuvent procéder à la vaccination sans ordonnance individuelle ou collective conformément au Protocole d’Immunisation du Québec (PIQ). Les infirmières québécoises peuvent alors influencer positivement la couverture vaccinale (Sauvageau & al, 2005). Le but de cette étude est d’évaluer les retombées de la formation VIP (Vaccination par les Infirmières/Infirmiers-Prévention) sur les pratiques vaccinales rapportées par les infirmières (N=12) de CSSS, auprès des parents d’enfants de 0-5 ans lors d’un refus parental. En premier lieu, nous avons identifié et décrit treize pratiques vaccinales en réponse à un refus parental. Par la suite, nous avons identifié des modifications dans certaines des treize pratiques rapportées tel qu’une augmentation dans la description des pratiques de correction des fausses croyances des parents, une amélioration de la justesse des pratiques d’explication et une personnalisation des pratiques décrites. En conclusion, la formation offerte aux infirmières doit permettre à celles-ci d’identifier les préoccupations parentales et d’y répondre adéquatement en utilisant une information juste et individualisée.

Guide pour délégués et déléguées sociaux: Médicaments et autres substances en milieux de travail

Le guide et les vidéos se veulent des outils de sensibilisation et d'information à l'usage des délégués sociaux et autres intervenants dans divers milieux de travail à travers le Québec.

La Cinéologie de l'entre-deux-guerres : les écrivains français et le cinéma

Cette thèse de doctorat porte sur l’évolution du discours critique et théorique sur le cinéma développé par les écrivains français de l’entre-deux-guerres (1918-1939). À une époque où le cinéma prend de plus en plus de place dans la société, les écrivains s’intéressent à cette nouveauté, y réfléchissent et tentent d’élaborer des canevas à partir desquels peut se former une cinéologie, c’est-à-dire, une écriture sur le cinéma. De très nombreux textes (articles, chroniques, essais, manifestes, préfaces, biographies), issus de publications diverses (revues de cinéma, revues littéraires, revues d’art, presse quotidienne, édition), témoignent de l’engouement pour ce qui sera rapidement présenté comme un art. S’inscrivant dans un vaste réseau de diffusion, ces textes aux prémisses essayistiques laissent une place centrale à la réflexion et sont représentatifs des tendances et des enjeux de l'époque. Ainsi, ils montrent les débats autour de l’acceptation du cinéma comme art tout comme les prises de position au sujet du parlant, ils abordent les relations avec la forme de représentation rivale qu’est le théâtre, ils témoignent de la modernité du nouveau média et en proposent des définitions mettant l’accent sur certains de ses aspects – thématiques (comme le rêve et l’inconscient), pratiques (comme la dépendance vis-à-vis de l’industrie et de la finance) et techniques (comme la photogénie et le rythme). Cette production textuelle doit également être abordée comme une mémoire du cinéma où se côtoient des figures (Charlie Chaplin, Douglas Fairbanks, ou encore Erich von Stroheim) et des films (The Cheat, Le Cabinet du Docteur Caligari, ou Hallelujah!) dont les seules évocations fonctionnent comme des citations et des arguments appuyant les propos. En plus de la richesse des idées proposées, l'étude de la posture, l’analyse des renvois intertextuels et des inventions lexicales montrent que des écrivains comme Louis Aragon, Blaise Cendrars, Pierre Mac Orlan, Jean Prévost ou encore Marcel Pagnol, ont largement contribué à l'élaboration d’un pan du savoir cinématographique et au développement d'un discours qui place l’expérience du cinéma et celle du spectateur au centre des préoccupations cinéphiliques.

Introduction to Knowledge Representation

Focussing on Open Data and the need for cleaning data