Caring for someone who has self-harmed or had suicidal thoughts

This guide provides important information on how to take care of yourself and your family member following a suicide attempt/suicidal thoughts or self-harm and highlights resources to help you move forward.The guide is divided into three parts:1. What happens during a visit to the Emergency Department (new name for A&E), GP or GP out-of-hours (OOH) department.2. What you need to know following your family member��'s discharge.3. Moving forward after your family member returns home.

IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.

Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-)-derived clones lysed target cells with high efficacy. In contrast, EM28(+)-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28.

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors.

Routine use of self-expanding venous cannulas for cardiopulmonary bypass: benefits and pitfalls in 100 consecutive cases.

OBJECTIVE: Assess the performance of self-expanding venous cannulas for routine use in open-heart surgery. METHODS: Prospective study in 100 unselected consecutive patients undergoing open-heart surgery with either remote or central smart venous cannulation. RESULTS: The study focuses on the 76 consecutive adult patients (mean age 59.2+/-17.3 years; 60 males, 16 females) undergoing surgical procedures with total cardiopulmonary bypass for either valve procedures (42/76 patients=55.3%), ascending aorta and arch repair (20/76 patients=26.3%), coronary artery revascularization (13/76 patients=17.1%) or other procedures (11/76 patients=14.5%) with 14/76 patients (18.4%) undergoing redo surgery and 6/76 patients (7.9%) undergoing small access surgery. The mean pump flow achieved by gravity drainage alone accounted for 5.0+/-0.6l/min (=114% of target) in the entire study population (n=76) as compared to the calculated, theoretical pump flow of 4.4+/-0.5l/min (p<0.0001). For the femoral cannulation sub-group (n=35) pump flow achieved by gravity drainage alone accounted for 4.9+/-0.6l/min (=114% of target) as compared to the calculated theoretical pump flow of 4.3+/-0.4l/min (p<0.0001). The corresponding numbers for trans-subclavian cannulation (n=7) are 5.2+/-0.5l/min (111%) for the pump flow achieved by gravity drainage as compared to the theoretical target flow of 4.7+/-0.4l/min. For the central cannulation sub-group (n=34) mean flow achieved by gravity drainage with a self-expanding venous cannula accounted for 5.1+/-0.7l/min (=116% of target) as compared to the calculated theoretical flow of 4.4+/-0.6l/min (p<0.0001). CONCLUSION: Full or more than target flow was achieved in 97% of the patients studied undergoing CPB with self-expanding venous cannulas and gravity drainage. Remote venous cannulation with self-expanding cannulas provides similar flows as central cannulation. Augmentation of venous return is no longer necessary.

Determinants of the educational use of digital learning materials: The mediating role of self-efficacy, perceived norm and attitude

Initiatives to stimulate the development and propagation of open educational resources (OER) need a sufficiently large community that can be mobilized to participate in this endeavour. Failure to achieve this could lead to underuse of OER. In the context of the Wikiwijs initiative a large scale survey was undertaken amongst primary and secondary school teachers to explore possible determinants of the educational use of digital learning materials (DLMs). Basing on the Integrative Model of Behaviour Prediction it was conjectured that self-efficacy, attitude and perceived norm would take a central role in explaining the intention to use DLMs. Several other predictors were added to the model as well whose effects were hypothesized to be mediated by the three central variables.All conjectured relationships were found using path analysis on survey data from 1484 teachers. Intention to DLMs was most strongly determined by self-efficacy, followed by attitude. ICT proficiency was in its turn the strongest predictor of self-efficacy. Perceived norm played only a limited role in the intention to use DLMs. Concluding, it seems paramount for the success of projects such as Wikiwijs to train teachers in the use of digital learning materials and ICT (e.g. the digital blackboard) and to impact on their attitude.

Using self organizing maps on compositional data

Self-organizing maps (Kohonen 1997) is a type of artificial neural network developedto explore patterns in high-dimensional multivariate data. The conventional versionof the algorithm involves the use of Euclidean metric in the process of adaptation ofthe model vectors, thus rendering in theory a whole methodology incompatible withnon-Euclidean geometries.In this contribution we explore the two main aspects of the problem:1. Whether the conventional approach using Euclidean metric can shed valid resultswith compositional data.2. If a modification of the conventional approach replacing vectorial sum and scalarmultiplication by the canonical operators in the simplex (i.e. perturbation andpowering) can converge to an adequate solution.Preliminary tests showed that both methodologies can be used on compositional data.However, the modified version of the algorithm performs poorer than the conventionalversion, in particular, when the data is pathological. Moreover, the conventional ap-proach converges faster to a solution, when data is \well-behaved".Key words: Self Organizing Map; Artificial Neural networks; Compositional data

Novel MLPA procedure using self-designed probes allows comprehensive analysis for CNVs of the genes involved in Hirschsprung disease.

Background: Hirschsprung disease is characterized by the absence of intramural ganglion cells in the enteric plexuses, due to a fail during enteric nervous system formation. Hirschsprung has a complex genetic aetiology and mutations in several genes have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. In this study, we have looked for CNVs in some of the genes related to Hirschsprung (EDNRB, GFRA1, NRTN and PHOX2B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach. Methods: CNVs screening was performed in 208 HSCR patients using a self-designed set of MLPA probes, covering the coding region of those genes. Results: A deletion comprising the first 4 exons in GFRA1 gene was detected in 2 sporadic HSCR patients and in silico approaches have shown that the critical translation initiation signal in the mutant gene was abolished. In this study, we have been able to validate the reliability of this technique for CNVs screening in HSCR. Conclusions: The implemented MLPA based technique presented here allows CNV analysis of genes involved in HSCR that have not been not previously evaluated. Our results indicate that CNVs could be implicated in the pathogenesis of HSCR, although they seem to be an uncommon molecular cause of HSCR.

Role of Notch signalling in intestinal epithelium

Résumé: Chez les mammifères, les intestins sont les organes ayant le plus haut taux de renouvellement cellulaire dans l'organisme. L'épithélium intestinal se renouvelle complètement en moins d'une semaine. Il se compose de projections (villosités) et d'invaginations (cryptes) qui ont toutes deux des fonctions bien distinctes. Les cellules de l'intestin sont constamment produites à partir de cellules souches, situées dans la crypte, qui se différencient en cellules proliférantes transitoires, puis en cellules caliciformes, de Paneth, entéroendocrine ou en entérocytes. Ces cellules migrent dans leurs lieux spécifiques pour accomplir leur fonction physiologique pour finalement mourir. A cours de mon travail de thèse, j'ai étudié le rôle de la voie de signalisation de Notch dans le renouvellement cellulaire et dans le processus de l'homéostase des cellules de l'intestin marin en utilisant le système Cre-loxP pour induire la délétion des gènes Notch1, Notch2, Jaggedl et RBP-Jk. Bien que l'inactivation de Notch1 avec ou sans Jagged1, ou celle de Notch2, n'aboutissent à aucun phénotype, une déficience pour RBP-Jk, ou pour Notch1 et Notch2 simultanément, conduit au développement d'un impressionnant phénotype. Au niveau de la crypte, une rapide et importante modification des cellules apparaît: les cellules proliférantes sont devenues des cellules caliciformes qui ont perdu la capacité de se renouveler. Ces résultats impliquent la voie Notch en tant que nouvelle clé de voûte dans le maintien des cellules qui s'auto-renouvellent dans l'épithélium intestinal. Un rôle similaire a été proposé pour la voie Wnt, laquelle n'est cependant, pas affectée dans nos souris. C'est pourquoi ces deux voies sont essentielles dans le maintien de la prolifération dans les cryptes intestinales. Ce travail a aussi proposé un mécanisme par lequel la voie Notch contrôlerait l'intégrité du cycle cellulaire dans les cellules de la crypte intestinale, ceci en inhibant la transcription d'un inhibiteur du cycle cellulaire, la protéine p27KIP1. De plus, l'inactivation de RBP-Jk dans les adénomes développés par les souris APCmin induisent la différenciation de cellules tumorales en cellules caliciformes. Comme autre effet, la localisation histologique des cellules de Paneth est également affectée par la délétion de RBP-Jk ou de Notch1/Notch2, suggérant un rôle pour la voie Notch dans le compartiment des cellules de Paneth. Finalement, ce travail démontre que les cellules progénitrices de l'intestin ont besoin d'une convergence fonctionnelle des voie Wnt et Notch. Ces résultats préliminaires peuvent être considérés comme un concept pour l'utilisation d'inhibiteurs de secrétase-γ (inhibiteurs de Notch) à des fins thérapeutiques pour les cancers colorectaux. Summary The mammalian intestine has one of the highest cellular turnover rates in the body. The complete intestinal epithelium is renewed in less than a week. It is divided into spatially distinct compartments in the form of finger-like projections (villi) and flask-shaped invaginations (crypts) that are dedicated to specific functions. Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate and home to their specific compartments before dying after having fulfilled their physiological function. In this thesis project, the physiological role of the Notch signalling cascade in the marine intestine was studied. Inducible tissue specific inactivation of Notch1, Notch2, Jagged1 and RBP-Jk genes was applied to assess their role in the maintenance of intestinal homeostasis and cell fate determination. The analysis unequivocally revealed that Notch1, Notch1 and Jagged1 combined as well as Notch2 are dispensable for intestinal homeostasis and lineage differentiation. However, deficiency of RBP-Jk as well as the simultaneous inactivation of both Notch1 and Notch2 receptors unveiled a striking phenotype. In these mice, a rapid and massive conversion of proliferative crypt cells into post-mitotic goblet cells was observed. These results identify the Notch pathway as a key player for the maintenance of the proliferative crypt compartment. A similar role was implicated for the Wnt cascade, which, however, was not affected in the different tissue specific Notch signalling deficient mice. Thus, the Wnt and Notch signalling pathways are essential for the self-renewal capacity of the intestinal epithelium. Furthermore, our results suggest a molecular mechanism for Notch signalling mediated control of cell cycle regulation within the crypt. The Notch cascade inhibits expression of the cyclin-dependent kinase inhibitor p27KIP1 and thereby maintains proliferation of the intestinal progenitor cells. In addition, the inactivation of RBP-Jk in adenomas developed by APCmin mice resulted in the differentiation of tumour cells into goblet cells. Finally, Notch deficiency affected differentiated Paneth cells, suggesting that Notch may play a role in the Paneth cell compartment. In summary, this work clearly demonstrates that undifferentiated, proliferative cells in intestinal crypts require the concerted activation of the RBP-Jk-mediated Notch signalling and the Wnt cascade. In addition, our preliminary results can be considered as a "proof-of-principle" for the use of γ-secretase inhibitors for therapeutic modalities for colorectal cancer.

Respiratory self-navigated postcontrast whole-heart coronary MR angiography: initial experience in patients.

PURPOSE: To assess the diagnostic performance of respiratory self-navigation for whole-heart coronary magnetic resonance (MR) angiography in a patient cohort referred for diagnostic cardiac MR imaging. MATERIALS AND METHODS: Written informed consent was obtained from all participants for this institutional review board-approved study. Self-navigated coronary MR angiography was performed after administration of a contrast agent in 78 patients (mean age, 48.5 years ± 20.7 [standard deviation]; 53 male patients) referred for cardiac MR imaging because of coronary artery disease (n = 40), cardiomyopathy (n = 14), congenital anomaly (n = 17), or "other" (n = 7). Examination duration was recorded, and the image quality for each coronary segment was assessed with consensus reading. Vessel sharpness, length, and diameter were measured. Quantitative values in proximal, middle, and distal segments were compared by using analysis of variance and t tests. A double-blinded comparison with the results of x-ray angiography was performed when such results were available. RESULTS: When patients with different indications for cardiac MR imaging were examined with self-navigated postcontrast coronary MR angiography, whole-heart data sets with 1.15-mm isotropic spatial resolution were acquired in an average of 7.38 minutes ± 1.85. The main and proximal coronary segments could be visualized in 92.3% of cases, while the middle and distal segments could be visualized in 84.0% and 55.8% of cases, respectively. Subjective scores and vessel sharpness were significantly higher in the proximal segments than in the middle and distal segments (P < .05). Anomalies of the coronary arteries could be confirmed or excluded in all cases. Per-vessel sensitivity and specificity for stenosis detection were 64.7% and 85.0%, respectively, in the 31 patients for whom reference standard x-ray coronary angiography results were available. CONCLUSION: The self-navigated coronary MR angiography sequence shows promise for coronary imaging. However, technical improvements are needed to improve image quality, especially in the more distal coronary segments.