Inheritance of ductile and brittle structures in the development of large rock slope instabilities: Examples from western Norway

The high density of slope failures in western Norway is due to the steep relief and to the concentration of various structures that followed protracted ductile and brittle tectonics. On the 72 investigated rock slope instabilities, 13 were developed in soft weathered mafic and phyllitic allochthons. Only the intrinsic weakness of such rocks increases the susceptibility to gravitational deformation. In contrast, the gravitational structures in the hard gneisses reactivate prominent ductile or/and brittle fabrics. At 30 rockslides along cataclinal slopes, weak mafic layers of foliation are reactivated as basal planes. Slope-parallel steep foliation forms back-cracks of unstable columns. Folds are specifically present in the Storfjord area, together with a clustering of potential slope failures. Folding increases the probability of having favourably orientated planes with respect to the gravitational forces and the slope. High water pressure is believed to seasonally build up along the shallow-dipping Caledonian detachments and may contribute to destabilization of the rock slope upwards. Regional cataclastic faults localized the gravitational structures at 45 sites. The volume of the slope instabilities tends to increase with the amount of reactivated prominent structures and the spacing of the latter controls the size of instabilities.

Composición en ácidos grasos de huevos y larvas de dentón (Dentex dentex L.) de hasta 40 días en condiciones de cultivo

Total lipid content and fatty acid (FA) composition of common dentex eggs spawned at different times and larvae reared under different culture conditions until 40 days post hatch (dph) were analysed in order to get a general pattern of lipid composition during larval development. Results were grouped according to the developmental stage of the larvae instead of age in dph. Saturated and monounsaturated fatty acids decreased along larval development, while polyunsaturated fatty acid (PUFA) content increased. The ratio of docosahexaenoic acid (DHA) / eicosapentaenoic acid (EPA) shifted from 4 – 5 in early developmental stages to lower than 1 after metamorphosis. Results suggest a subdivision of the larval development into two stages of opposite FA requirements.

SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage.

SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been described in patients with Aicardi-Goutières syndrome (AGS), a congenital autoimmune disease. In a previous longitudinal whole genome sequencing study of chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event. Here, we describe an AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell proliferation and survival and engages in specific protein interactions in response to DNA damage. We propose that SAMHD1 may have a function in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.

NICaN Regional Supportive & Palliative Care Network

NICaN Regional Supportive & Palliative Care Network Friday 30th May 2008 Lecture Theatre, Fern House Antrim 2.00 pm - 5.00 pm Welcome, Introductions Stuart MacDonnell, Chair of the Supportive and Palliative Care network welcomed everyone to the meeting. This meeting had been rescheduled to accommodate the validation workshop for the regional palliative care model, which took place on Friday,18th April. Acknowledging the full agenda, several items were pulled forward to accommodate speakers SPC_0809_03 Modernisation and Reform of Supportive and Palliative care Mr MacDonnell welcomed Dr Sonja McIlfatrick and Dr Donna Fitzimons, members of the Phase 1 Project Team for the Modernisation and Reform of palliative care. Their presentation highlighted the journey taken by the Project Team since January 2008 - May 2008. Seeking to deliver the network vision, for any person with palliative care need, cancer or non - cancer, the project team incorporated several methodologies. The literature review identified best practice. An assessment of need including epidemiological data and review of service provision. Consultation reflected the engagement with patients, carers and professional forums, primary care and non-malignant focus groups. The breadth of consultation confirmed the evidence for the identified components of the model. These were validated at the April workshop. External review of the work was provided by Dr Phil Larkin (Galway Uni) Prof David Clark (End of Life Care Observatory, Lancaster University) and Mr Bob Neillans (Chair of the Mid Trent Palliative care network, which has been involved in the Delivering choice programme within Lincolnshire). The Guiding Principles of the model reinforced Patient and family centred care, enhanced community provision and supported by specialists. The components of the model are · Identification of patient with Palliative careened · Holistic Assessment · Integration of services · Coordination of care · End of Life Care and Bereavement Care The consultation process also highlighted the need for Increased Public and Professional Awareness. This was recognised as an encompassing component. Underpinning the model is the need for robust Education and common core values e.g. dignity, choice, advocacy, empowerment, partnership working. Stuart MacDonnell, who also chaired the steering group during the project, congratulated the Project Team for delivering the comprehensive document on schedule. The Report has been submitted to the NICaN Board and the DHSSPSNI. In addition, an outline for Phase 2 of this work has been submitted. Mr MacDonnell recognised that there is real opportunity for palliative care to benefit from the DHSSPSNI commitment to concrete developments. Phase 2 will progress the current high-level components of the model into quality services developments at a local level, demonstrating integration throughout. The methods propose continued engagement with the Delivering Choice Programme enabled through a Central and also Local Teams. The report and the Appendices care available on the NICaN website www.nican@n-i.nhs.uk SPC_0809_01 Chairman's Business · Update on the Cancer Service Framework, the document has been submitted and presented to the Departmental Programme Board. Next stages will include the review of costs and development of a implementation guidance It is hoped that the completed document should be available for public consultation in Autumn 2008. with a launch of the framework document and accompanying implementation guide in Spring 2009. Some funding has already been identified to advance key areas of work including, Advanced communication skills training, peer review and an appointment of a post to develop the cancerni.net, focusing on children and e-learning tools. · Children's and Adolescent Cancer network group , Liz Henderson is to convene a group to consider how this is to be taken forward. · NICaN appointments Recognition was given to the significant contribution made by Dr Gerard Daly during his position as NICaN Lead Clinician, particularly throughout the early establishment of the NICaN. Dr Dermott Hughes (Western Trust) has been appointed as the NICaN Medical Director. The Primary Care Director post has been advertised and it is hoped that the Director of Network will be advertised later in Summer. Endorsement of End of Life care paper. The Paper was presented and endorsed at the March 2008 NICaN Board meeting. Mr David Galloway (Director of Secondary Care) emphasised the need for this important work to be recognised within the regional model to ensure that it is reflected in future models of service delivery Congratulations were again echoed to the Chair of the End of Life Group for this work, Dr Glynis Henry, and the working group Other recognition Mr MacDonnell congratulated the significant achievements across the network. These include: · Dr Francis Robinson (Consultant Palliative Medicine, Western Trust) Awarded - Consultant of the year at the NI Health Care awards. · Mrs Evelyn Whittaker Hospice Nurse Specialist, NI Hospice, Joint Second Prize in the Development award within the International Journal of Palliative Nursing Awards, for her work in development of palliative care education in nursing homes. · Mr Ray Elder is the newly appointed Team Leader of Community Palliative care, SE Trust. · Mrs Bridget Denvir, who managed the establishment of one of the first community multiprofessional palliative care teams is moving to work with establishing integrated teams within the Belfast Trust. Bridget has been an active core member of the network and here contribution has been much appreciated. Mrs Sharon Barr will attend in future. SPC_0809_02 Minutes & matters Arising from Meeting, 13th December 2007 No amendments were made to the draft minutes from the December meeting. These will be posted on the NICaN website for future reference. Palliative Care Research Following consultation, the response to the business case for the All Ireland Institute was forwarded on 22 February 2008 to Prof David Clark. Prof Judith Hill informed the group that terms of tender are now being developed. Awareness raising across academic institutions continues to engage interest in potential partnerships. Atlantic Philantrophies have offered financial support to the venture and match funding is being sought from across jurisdictions. Previous discussions at Network meetings have endorsed the need to establish a work strand for research and development within palliative and end of life care. To identify the body of interested parties and explore the strengths and weaknesses of a collaborative model for research, a workshop, - Building collaboration for Palliative and End of life Care Research -will take place on 4 June 10am - 2pm.in the Comfort Hotel.Antrim, The workshop will be chaired by Prof David Clark, Director of the International Observatory on End of Life Care. Prof Shelia Payne, Help the Hospices Chair in Hospice Studies and co director of the Cancer Experiences Collaborative will present the Experiences and Results from Research Collaborative. Feedback from this event will be brought back to the next meeting in September. SPC_0809_04 Patient Information pathways - a pathway for advanced disease Ms Danny Sinclair, NICaN Regional Coordinator for Patient Information informed the network of how patient information pathways have been developed in line with the Cancer Services Collaborative. Emerging themes, with regard to information needs of patients with advanced disease, are being identified from the work undertaken across the tumour groups. It is important to identify all information needs to develop a generic pathway of information resources for advanced disease to be endorsed by the Supportive and Palliative care network. This could be used across the all tumour specific information pathways and across organisational boundaries. The resulting pathway could potentially be used for non- cancer condition. A group is to be established to take this work forward. The group will: · Develop a list of advanced disease information themes · .Identify when they become relevant for the patient or their carer · .Identify existing resources · .Develop resources where needed · .Participate or nominate when review is required Dr Sheila Kelly nominated Helen Hume (SETrust) Paula Kealey will also contribute to this work; a nomination from the Patient and Public Information Forum has also been identified. A date will be circulated across the network to engage further interest and establish group SPC_0809_08 Development of a Regional Syringe Driver Prescription Chart Ms Kathy Stephenson reported that the second consultation of the draft regional syringe driver prescription chart and the focus group discussions, Pilots of the chart are to be undertaken within Trust, Hospices and General Practices. SPC_0809_05 A framework for Generalist and Specialist Palliative and End of Life Care Competency Dr Kathleen Dunne, lead of the Education works strand, reported on the findings following consultation of the Education framework. The report was widely appreciated across the network and valued as a significant and timely document for the commissioning of generalist and specialist adult palliative care education. Mr MacDonnell congratulated Dr Dunne and the members of the education workstrand for developing the framework aligning its significance to the underpinning needs of the regional model Amendments will be made to the document and then forwarded to the NICaN Board for endorsement. A process of implementation will be explored and reported to the network group at the September meeting. Key target areas for generalist palliative care education were highlighted within care of the elderly and general medicine. . SPC_0809_06 Pallcareni.net-a website for people with palliative care needs Ms Danny Sinclair, reminded the group of the pending amalgamation of the CAPriCORN and NICaN website. The resulting new web address will be www. cancerni.net. Recurrent funding has been secured to ensure the development of the supportive and palliative care website.www.Pallcareni.net The new website will host good information for people with palliative care needs, regardless of diagnosis. It will be accessible via the cancerni.net portal or independently as the pallcareni portal. It will signpost people with palliative care needs to condition- specific websites. The website will also enable the communication needs of the NI Regional Supportive & Palliative Care Network. This is a very significant method of seeking to enable greater understanding of palliative care for public and professionals, as highlighted within the regional model. Currently the material from the CAPriCORN website is being migrated onto cancerni and /or pallcareni.net as appropriate. To enable the further development of this opportunity a steering group of interested individuals is to be established. Their role will be to: · Drive the development of the website so it meets the needs of public and professionals through the sourcing and development of additional content · Identify any support that is needed, e.g. technical support · Review the website as a whole as it grows (coordinating condition-specific developments) · Review the functions of the website to aid communication throughout the Supportive and Palliative care network The steering group representation should reflect the constituencies within the Supportive and Palliative Care network. Current expressions of interest have come from Heather Reid and Valerie Peacock. A date will be circulated across the network to engage further interest and establish group SPC_0809_07 Update of Guidelines workstrand Dr Pauline Wilkinson presented the current work within the guidelines workstrand. 1. Brief Holistic Assessment & Referral Criteria to Specialist Palliative Care The development of an Holistic assessment Tool will help to identify holistic need at generalist and specialist level. Recognition of complex need prompts appropriate referral to specialist palliative care. The regional referral form is compatible with the Minimum Data set. The final drafts of this work are to be circulated widely, inclusive of service framework groups, primary care, secondary care and the supportive and palliative care network. Consultation will take place during June and July. Piloting of the forms will also be undertaken. 2. Control of Pain in Cancer Patients The original guidelines where developed 2003 and are now ready for review. The Mapping exercise, undertaken in May 2007, highlighted that the Guidelines were poorly adopted. The group have reviewed the pending SIGN 2 guidelines for pain with regard to practice in Northern Ireland. These are highly evidence based and are due to be launched this Summer. Whilst an excellent resource their comprehensiveness limits their readability, this may result in poor compliance. The Guidelines group feel it is important to have accessible and user-friendly guidelines particularly for Generalists and Out of hours. There are examples of good work that has taken place across the province, but there is a need for regional consistency. Dr Wilkinson has contacted Dr Carolyn Harper (Deputy CMO) and GAIN with regard to enabling funding to progress this work. The Guidelines group hope to approach the NICaN Primary Care Group to work in collaboratively on this piece, based on the templates already available. The works should be available in both electronic and paper versions. 3. Care of the dying & Breaking bad news Dr Gail Johnston has now completed an Audit of the Care of the Dying Pathways within the EHSSB. Gail is also seeking to examine to what extent the Regional Guidelines for Breaking Bad News are being implemented in the EHSSB with a view to identifying the need for further training or organisational structures that would facilitate future uptake. 4. Advances in new Technology Syringe Drivers Dr Wilkinson reported on a presentation made to the guidelines group by Mr Jim Elliot, Principle Engineer, Cardiology & Ann McLean, and Macmillan Palliative Care Nurse RVH. There is increasing concern with regard to how devices meet the recommended safety standards and how to reduce error. New devices have 3 point checking, automatic detection of syringe, automatic flow rates, full range of alarms, battery status and data download to provide an event log. There are now 2 companies in UK who have devices that meet these safety criteria. The current Graseby syringe drivers, which have been on the market and used predominately within Northern Ireland over the past 27 years Most new devices are not compatible with the regionally available monoject syringe, however contractual changes will lead to the withdrawal of the monoject syringes in October 2008. The Guidelines group supports a regional approach to this matter. This was echoed in the Supportive and Palliative care network. An option appraisal, identifying costs, and training issues should be developed through the engagement with Trusts and DHSSPSNI. The issue of Patient safety should be raised with the DHSSPSNI. SPC_0809_09 Evaluation of Supportive and Palliative Care network Deferred to next meeting. . SPC_0809_10 Emerging Issues Mrs Anne Coyle, Bereavement Coordinator, Southern Trust, announced that the Regional Bereavement Strategy is soon to be released. Anne supported the close alignment between the content of the strategy and the work of the regional model and other workstrands within the Supportive and Palliative care network. Ms Eleanor Donaghy, Transplant Coordinator, briefly highlighted the issue of tissue donation. Each year Northern Ireland has a dearth of corneal donations. There is no upper age limit for donation and retrieval is not limited by a cancer diagnosis. Recipients do not require immunosuppressive and the transplant is lifelong. The National Blood Service provided coordination of this donation they may be contacted via 07659180773. It is hoped that Mrs Coyle and Ms Donaghy could provide more comprehensive presentations at a future meeting. Events · Irish Psycho- Oncology Group Seminar, Cork 6 June, Exploring the Struggle for meaning in Cancer · Integrated Care: Putting Research into Practice, 13June, Trinity College, Dublin · Macmillan online conference Friday 13 June 2008, 9am - 5pm · Delivering effective end of life care: developing partnership working 15 Oct 2008, 9.30 -4.15 pm London Network Meeting was closed at 5.00pm SPC_0607_ Dates of Future Meetings (please note the change of venue) 10th September 2008, 1.30 - 5pm venue to be decided15th January 2009, 1.30 - 5pm venue to be decided12th May 2009, 1.30 - 5pm venue to be decided Attendances Apologies Stuart MacDonnellLorna NevinSonja McIlfatrick Donna FitzsimonsKathleen DunnePauline WilkinsonKathy StephensonSheila KellyMarie Nugent,Anne CoyleFiona GilmourJudith HillLorna DicksonMargaret CarlinLoretta GribbenYvonne Duff Lesley NelsonLiz HendersonSue FosterCathy PayneGraeme PaynePatricia MageeGeraldine WeatherupPaula KealyCaroline McAfeeLinda WrayValerie PeacockAnn McCleanRay Elder Martin BradleyHelen HumeGillian RankinHeather MonteverdeJulie DoyleAlison PorterYvonne SmythLiz Atkinson,Glynis HenryMaeve HullyCaroline HughesAnn FinnBob BrownSharon BarrJulie DoyleJanis McCulla .

Facteurs endogènes et exogènes influençant l'écriture manuelle chez l'enfant

Introduction L'écriture manuelle fluide et automatisée constitue, avec la lecture, les fondements au développement des compétences scolaires. En effet, l'enfant peut développer le langage écrit avec l'acquisition de l'écriture, il a besoin d'une écriture manuelle automatisée lors d'évaluations scolaires écrites. De plus, la sollicitation de l'écriture manuelle augmente au cours de la scolarité, que ce soit au niveau de l'endurance, de la vitesse ou de la qualité. L'acquisition de l'écriture requiert des processus cognitifs, linguistiques et perceptivomoteurs, définis en tant que facteurs internes ou endogènes (Beeson et al., 2003) et résulte d'une démarche d'enseignement et d'un processus d'apprentissage constituant des facteurs externes ou exogènes. Les perturbations de l'acquisition de l'écriture sont nommées de différentes manières dans la littérature scientifique. Les chercheurs anglo-saxons convoquent la notion de faible écriture manuelle (poor handwriting), de troubles grapho-moteurs ou de difficultés d'écriture (Weintraub & Graham, 2000 ; Jongmans, Smits-Engelsman, & Schoemaker, 2003 ; Volman, van Schendel, &Jongmans, 2006) qui se caractérisent par une absence de régularité du tracé et/ ou de l'espace entre les mots, par des lettres ambiguës (Rosenblum, Weiss, & Parush, 2006). Les auteurs francophones, le plus souvent de formation médicale (Gubbay & de Klerk, 1995 ; Mazeau, 2005), utilisent plus fréquemment le diagnostic de dysgraphie qui renvoie à des difficultés d'assemblage de ronds et de traits pour former une lettre perturbant ainsi l'apprentissage de l'écriture (Mazeau, 2005). Selon Mazeau, la dysgraphie fait partie des troubles d'apprentissage. Les conséquences d'une faible écriture manuelle sont multiples. Si l'écriture n'est pas automatisée, l'enfant est placé dans une situation de double tâche nécessitant une attention focalisée à la fois sur l'acte d'écrire et sur le raisonnement nécessaire pour réaliser les exigences d'une tâche scolaire (Berningér et al., 1997). Si l'enfant se concentre sur la formation des lettres et le contrôle des mouvements, le raisonnement nécessaire à l'application de règles de grammaire et d'orthographe est perturbé tout comme la qualité des idées lors d'une composition. L'enfant présentant une écriture lente ne parviendra pas à finaliser son travail dans les situations de tests. Les difficultés d'écriture manuelle constituent un facteur de prédiction des troubles d'apprentissage (Harvey & Henderson, 1997 ; Simner, 1982) et elles sont fréquemment citées parmi les causes de la littératie. Car, comme le relèvent Berninger, Mizokawa et Bragg (1991), l'enfant présentant des difficultés d'écriture manuelle aura tendance à éviter toute activité d'écriture renforçant ainsi l'écart avec ses pairs dans ce domaine. Si ces comportements d'évitement se situent dans la période d'apprentissage de l'écriture, ils perturberont la mémorisation des lettres. En effet, la mémorisation des lettres est meilleure lorsque l'apprentissage se fait en situation d'écriture manuelle qu'en situation de lecture uniquement (Longcamp, Boucard, Guilhodes, & Velay, 2006). Par ailleurs, les épreuves dont la qualité de l'écriture est faible font l'objet d'évaluation moins favorable que celles dont l'écriture est plus facilement lisible. Les enseignants/es seraient alors moins persévérants/es dans leur lecture et plus sévères lors de la notation d'une rédaction. Ils, elles développeraient une faible perception des compétences en composition lorsqu'ils, elles sont confrontés/es à une épreuve dont la qualité est peu fluide et peu lisible (Alston & Taylor, 1987). L'identification des difficultés d'écriture peut se fairé de différentes manières (Kozatiek & Powell, 2002 ; Simons & Thijs, 2006 ). D'une part, l'appréciation de la qualité et de la vitesse d'écriture manuelle peut être subjective avec l'avis de l'enseignant et, d'autre part, objective avec l'utilisation de tests standardisés comportant des critères permettant de mesurer la vitesse et la qualité de l'écriture. Les conditions de passation des évaluations peuvent varier (copie, dictée ou composition) et influencer la vitesse et la qualité de l'écriture. La vitesse est moindre et la taille des lettres est inférieure en situation de composition qu'en situation de copie tandis que la régularité du tracé est plus stable en situation de copie que lors d'une composition. Si le dépistage et l'identification des difficultés d'écriture contribuent à la prévention de risques ultérieurs tels que de faibles compétence en littératie, la compréhension des causes de ces difficultés permettra le développement de moyens de remédiation de ces difficultés. Dans la littérature scientifique traitant de cette problématique, des facteurs endogènes ou exogènes peuvent être identifiés. Les facteurs endogènes regroupent autant la maturation développementale et le genre que les fonctions sensorimotrices telles que les dextérités manuelle et digitale, l'intégration visuomotrice, la visuoperception, l'attention visuelle et les fonctions cognitives. En outre, les troubles du développement tels qu'un trouble du langage, un déficit de l'attention ou un Trouble de l'acquisition de la coordination (TAC) (DSM-IV) (American Psychiatric Association, 2003) peuvent perturber l'acquisition de l'écriture. Les facteurs exogènes correspondent soit aux facteurs environnementaux tels que la position de l'enfant ou l'outil scripteur utilisé, soit aux modalités et à la durée de l'enseignement de l'écriture. En effet, la durée de l'enseignement de l'écriture et les modalités pédagogiques contribuent à marquer les différences interindividuelles pour la qualité et pour la vitesse de l'écriture. Actuellement, l'enseignement de l'écriture est, dans la plupart des programmes scolaires, intégré dans le cadre d'autres cours et ne fait pas l'objet d'un enseignement spécifique. Cette pratique entraîné un auto-apprentissage de la part de l'enfant et, par conséquent, un apprentissage implicite de l'écriture alors que les bénéfices d'un enseignement explicite ont été largement mis en évidence par Willingham et Goedert-Eschmann (1999). En effet, ces auteurs ont montré qu'un enseignement explicite favorise l'acquisition, la performance et le transfert d'apprentissage de manière plus importante que l'apprentissage implicite. Paradoxalement, alors que l'enseignement de l'écriture tend à être délaissé dans les programmes scolaires, les études mettant en évidence l'efficacité de l'enseignement de l'écriture (Berninger et al., 1997 ; Jongmans, Linthorst-Bakker, Westenberg & SmitsEngelsman et al., 2003 ; Schoemaker, Niemeijer, Reynders, & Smits-Engelsman , 2003) sont nombreuses. Leurs résultats montrent que l'enseignement d'une seule catégorie d'écriture (liée ou scripte) est plus efficace que l'enseignement de deux catégories d'écriture scripte en début d'apprentissage et écriture liée dans un second temps. Un enseignement régulier et intensif consacré à l'écriture au début de la scolarité va permettre une acquisition plus rapide de l'écriture et de la lecture (Graham & Weintraub, 1996 ; Denton, Cope & Moser, 2006). Selon Berninger, Abbot, Abbot, Graham et Richards (2002), la lecture et l'écriture devraient faire l'objet d'un enseignement coordonné et harmonisé. L'enseignement de l'écriture favorisant les liens avec les contextes d'utilisation de l'écriture montre une efficacité plus grande que lorsqu'il est déconnecté de son contexte (Denton, Cope, & Moser, 2006). L'enjeu d'une automatisation de l'écriture de qualité est important et relève d'une priorité afin de permettre aux enfants de développer de manière optimale leurs compétences académiques. Lorsque des troubles d'écriture sont constatés, l'identification des causes liées à ces difficultés tout comme une prise en charge spécifique faciliteront l'acquisition de cette compétence fondamentale (Berninger et al., 1997). Dans ces perspectives, cette thèse vise à identifier les facteurs endogènes et les facteurs exogènes intervenant dans l'écriture manuelle, que ce soit au niveau de la qualité ou de la vitesse de l'écriture. Au niveau théorique, elle développe l'étai des connaissances dans le domaine de l'écriture en neuropsychologie, en neurosciences et en sciences du mouvement humain. Elle présente, dans une perspective développementale, les modèles de l'apprentissage de l'écriture ainsi que les étapes d'acquisition de l'écriture tout en considérant les différences liées au genre. Ensuite, la description des difficultés d'écriture manuelle précède les moyens d'évaluation de l'écriture. Un chapitre est consacré aux fonctions perceptivomotrices et cognitives influençant l'écriture. Puis, comme les difficultés d'acquisition de l'écriture manuelle font partie du TAC, ce trouble est développé dans le chapitre 5. Enfin, les facteurs exogènes sont présentés dans le chapitre 6, ils comprennent les conditions environnementales (position de l'enfant, types de papiers, types d'outils scripteurs) ainsi que les dimensions d'un programme d'enseignement de l'écriture manuelle. Les effets des programmes de remédiation ou d'enseignement intensif de l'écriture sont traités en dernière partie du chapitre 6. Cette thèse est composée d'une partie de recherche fondamentale et d'une partie de recherche appliquée. La recherche fondamentale, qui comprend deux étapes d'investigation (Etudes 1 et 2), a pour objectifs d'identifier les facteurs endogènes prédictifs d'une écriture manuelle non performante (dextérités digitale et manuelle, intégration visuomotrice ou visuoperception) et d'investiguer les relations entre la lecture, l'attention visuelle, la mémoire audtive et l'écriture manuelle. De plus, elle déterminera la prévalence du TAC parmi les enfants présentant une faible écriture manuelle. La recherche appliquée comporte deux expérimentations. La première expérience a pour but de mesurer les effets d'un programme d'enseignement de l'écriture introduit en fin de deuxième année primaire visant à permettre aux enfants les plus faibles dans le domaine de l'écriture d'améliorer leurs performances. La seconde expérience analyse les effets d'un programme d'enseignement intensif de l'écriture manuelle qui s'est déroulé au début de la première année de scolarité obligatoire. L'acquisition de l'écriture est complexe tant au niveau du contróle moteur que du codage phonème -graphème ou de l'attention. L'écriture manuelle, en tant que compétence de base dans le développement des acquisitions scolaires, demeure tout au long de la scolarité et de la vie professionnelle, une compétence incontournable malgré le développement des nouvelles technologies. Remplir un formulaire, prendre des notes dans une séance ou à un cours, signer des documents, consigner des notes dans des dossiers, utiliser des écrans tactiles constituent des activités nécessitant une écriture manuelle fonctionnelle.

Cancer Inequalities in the East Midlands

This report by Trent Cancer Registry and EMPHO provides important information on variations in the incidence, mortality and survival for the four most common cancers diagnosed in people living in the East Midlands (lung, colorectal, breast and prostate). In particular, it highlights large differences in incidence and mortality rates between different parts of the Region and identifies significant gaps in survival after diagnosis between the most affluent and most deprived areas.

Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection

Enterohemorrhagic Escherichia coli, including the serotype O157:H7 that is most commonly identified with human disease, cause both sporadic cases and outbreaks of non-bloody diarrhea and hemorrhagic colitis. In about 10% of infected subjects, the hemolytic uremic syndrome (hemolytic anemic, thrombocytopenia, and acute renal failure) develops, likely as a consequence of systemic spread of bacterial-derived toxins variously referred to as Shiga-like toxin, Shiga toxin, and Verotoxin. Increasing evidence points to a complex interplay between bacterial products - for example, adhesins and toxins - and host signal transduction pathways in mediating responses to infection. Identification of critical signaling pathways could result in the development of novel strategies for intervention to both prevent and treat this microbial infection in humans.

Botulinum toxin A in non-dystonic tremors.

The present pilot study evaluated the effect of botulinum toxin A on primarily non-dystonic tremors using accelerometry in a single-blind, placebo-controlled design. Resting, postural, intention, or head tremor were assessed before and approximately 1 month after intramuscular saline and botulinum toxin A (25-50 U) respectively. Half of the patients showed > or = 30% placebo effect. Tremor in 10 of 17 patients (60%) studied improved further after botulinum toxin A (range 30-95%), exceeding the placebo effect by > or = 30%. Nine patients demonstrated clinically significant focal weakness in the extensor muscles after botulinum toxin A which interfered with fine movements. Patients were subdivided into PD-like and ET-like tremor(s). Both groups experienced large placebo effects for resting tremor, with little or no further improvement after botulinum toxin A. The improvement in postural tremor after botulinum toxin A, of 40% in the PD-like and 57% in the ET-like groups, however, was approximately twice that of placebo. In conclusion, botulinum toxin A exerts a modest tremorlytic effect, however the dose, and its distribution over the sites injected, need to be optimised to minimise focal weakness.

A large study of androgen receptor germline variants and their relation to sex hormone levels and prostate cancer risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol.

Neural crest cell survival is dependent on Rho kinase and is required for development of the mid face in mouse embryos.

Neural crest cells (NCC) give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia.

Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures.

The epithelial sodium channel (ENaC) is responsible for Na(+) and fluid absorption across colon, kidney, and airway epithelia. Short palate lung and nasal epithelial clone 1 (SPLUNC1) is a secreted, innate defense protein and an autocrine inhibitor of ENaC that is highly expressed in airway epithelia. While SPLUNC1 has a bactericidal permeability-increasing protein (BPI)-type structure, its NH2-terminal region lacks structure. Here we found that an 18 amino acid peptide, S18, which corresponded to residues G22-A39 of the SPLUNC1 NH2 terminus inhibited ENaC activity to a similar degree as full-length SPLUNC1 (∼2.5 fold), while SPLUNC1 protein lacking this region was without effect. S18 did not inhibit the structurally related acid-sensing ion channels, indicating specificity for ENaC. However, S18 preferentially bound to the βENaC subunit in a glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic fibrosis (CF) lung disease. Unlike control, CF human bronchial epithelial cultures (HBECs) where airway surface liquid (ASL) height was abnormally low (4.2 ± 0.6 μm), addition of S18 prevented ENaC-led ASL hyperabsorption and maintained CF ASL height at 7.9 ± 0.6 μm, even in the presence of neutrophil elastase, which is comparable to heights seen in normal HBECs. Our data also indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase, suggesting that it may still be active during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC by the S18 peptide suggests that this peptide may be suitable for treating CF lung disease.

Neutralising antibodies for Mayaro virus in Pantanal, Brazil

The Pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in South America. A serosurvey for Mayaro virus (MAYV), eastern (EEEV), western (WEEV) and Venezuelan (VEEV) equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. Sera were tested for specific viral antibodies using plaque-reduction neutralisation test. From a total of 748 equids, of which 264 were immunised with vaccine composed of EEEV and WEEV and 484 had no history of immunisation, 10 (1.3%) were seropositive for MAYV and two (0.3%) for VEEV using criteria of a ≥ 4-fold antibody titre difference. Among the 484 equids without history of immunisation, 48 (9.9%) were seropositive for EEEV and four (0.8%) for WEEV using the same criteria. Among the sheep, five were sero- positive for equine encephalitis alphaviruses, with one (0.4%) for EEEV, one (0.4%) for WEEV and three (1.3%) for VEEV. Regarding free-ranging caimans, one (1.1%) and three (3.4%), respectively, had low titres for neutralising antibodies to VEEV and undetermined alphaviruses. The neurological disorder outbreak could not be linked to the alphaviruses tested. Our findings represent strong evidence that MAYV and all equine encephalitis alphaviruses circulated in the Pantanal.

Improved earthquake response via simulation and integrated space- and ground-based technologies: the TREMOR proposal

Earthquakes occurring around the world each year cause thousands ofdeaths, millions of dollars in damage to infrastructure, and incalculablehuman suffering. In recent years, satellite technology has been asignificant boon to response efforts following an earthquake and itsafter-effects by providing mobile communications between response teamsand remote sensing of damaged areas to disaster management organizations.In 2007, an international team of students and professionals assembledduring theInternational Space University’s Summer Session Program in Beijing, Chinato examine how satellite and ground-based technology could be betterintegrated to provide an optimised response in the event of an earthquake.The resulting Technology Resources for Earthquake MOnitoring and Response(TREMOR) proposal describes an integrative prototype response system thatwill implement mobile satellite communication hubs providing telephone anddata links between response teams, onsite telemedicine consultation foremergency first-responders, and satellite navigation systems that willlocate and track emergency vehicles and guide search-and-rescue crews. Aprototype earthquake simulation system is also proposed, integratinghistorical data, earthquake precursor data, and local geomatics andinfrastructure information to predict the damage that could occur in theevent of an earthquake. The backbone of these proposals is a comprehensiveeducation and training program to help individuals, communities andgovernments prepare in advance. The TREMOR team recommends thecoordination of these efforts through a centralised, non-governmentalorganization.