Development of a Three Dimensional Multiscale Computational Model of the Human Epidermis

Transforming Growth Factor (TGF-β1) is a member of the TGF-beta superfamily ligand-receptor network. and plays a crucial role in tissue regeneration. The extensive in vitro and in vivo experimental literature describing its actions nevertheless describe an apparent paradox in that during re-epithelialisation it acts as proliferation inhibitor for keratinocytes. The majority of biological models focus on certain aspects of TGF-β1 behaviour and no one model provides a comprehensive story of this regulatory factor's action. Accordingly our aim was to develop a computational model to act as a complementary approach to improve our understanding of TGF-β1. In our previous study, an agent-based model of keratinocyte colony formation in 2D culture was developed. In this study this model was extensively developed into a three dimensional multiscale model of the human epidermis which is comprised of three interacting and integrated layers: (1) an agent-based model which captures the biological rules governing the cells in the human epidermis at the cellular level and includes the rules for injury induced emergent behaviours, (2) a COmplex PAthway SImulator (COPASI) model which simulates the expression and signalling of TGF-β1 at the sub-cellular level and (3) a mechanical layer embodied by a numerical physical solver responsible for resolving the forces exerted between cells at the multi-cellular level. The integrated model was initially validated by using it to grow a piece of virtual epidermis in 3D and comparing the in virtuo simulations of keratinocyte behaviour and of TGF-β1 signalling with the extensive research literature describing this key regulatory protein. This research reinforces the idea that computational modelling can be an effective additional tool to aid our understanding of complex systems. In the accompanying paper the model is used to explore hypotheses of the functions of TGF-β1 at the cellular and subcellular level on different keratinocyte populations during epidermal wound healing

Kwaliteit van leven bij dementie

In de literatuur worden verschillende definities van ‘kwaliteit van leven’ gevonden. Dit roept de vraag op welke domeinen als belangrijk worden gezien door mensen met dementie zelf. In een exploratieve studie werden de meningen van mensen met dementie (thuiswonend en verblijvend in verpleeghuizen) vergeleken met die van professionele zorgverleners en met meetinstrumenten voor kwaliteit van leven bij dementie. Gegevens werden verzameld door middel van interviews, focusgroepen en literatuurstudie. De meeste kwaliteit- van-levendomeinen die door mensen met dementie belangrijk werden gevonden, werden ook genoemd door de professionele zorgverleners en gevonden in meetinstrumenten. Sommige domeinen werden echter niet genoemd door professionals (‘gevoel voor esthetiek’, ‘financiële situatie’, ‘nuttig zijn/zingeving’ en ‘spiritualiteit’) of niet gevonden in de meetinstrumenten (‘veiligheid en privacy’, ‘zelfbeschikking en vrijheid’, ‘nuttig zijn/ zingeving’ en ‘spiritualiteit’). Dit wijst op mogelijke verschillen in perspectief tussen mensen met dementie enerzijds en hun zorgverleners en onderzoekers anderzijds. Vervolgens is onderzocht in hoeverre professionals zich richten op de kwaliteit-vanlevendomeinen die mensen met dementie belangrijk vinden. Zorgverleners van 29 afdelingen en 3 dagbehandelingen van 13 verpleeghuizen en 12 ontmoetingscentra vulden een vragenlijst in (N=374). Zij gaven aan zich tenminste in enige mate te richten op de meeste domeinen die als relevant werden genoemd door mensen met dementie, maar in beperkte mate op ‘financiële situatie’ en ‘nuttig zijn/ zingeving’. Zorgverleners die betrokken zijn bij dagbesteding richtten zich meer dan zorgverleners die 24-uurszorg leveren op de domeinen ‘gehechtheid’, ‘plezier in activiteiten’, ‘gevoel voor esthetiek in leefomgeving’ en ‘nuttig zijn, zingeving’

Blood biomarkers for the diagnosis of acute cerebrovascular diseases: a prospective cohort study

<p><b>Background:</b> The diagnosis of stroke or TIA in the emergency department is difficult, though important for early treatment. Circulating biomarkers might improve upon clinical assessment at admission.</p> <p><b>Methods:</b> We recruited symptomatic patients with suspected stroke or TIA and drew blood soon after admission. Each patient was assessed with the Face Arm Speech Test (FAST). We measured a panel of 15 circulating inflammatory, thrombotic, cardiac, and cerebral tissue damage biomarkers. Improvement in diagnostic performance was assessed by adding biomarkers to the FAST in logistic regression models to predict a final diagnosis of stroke or TIA (verified by expert review and imaging).</p> <p><b>Results:</b> 405 patients had suspected stroke: 285 with TIA or stroke (230 definite or probable ischemic stroke, 40 TIA, 15 hemorrhagic stroke) and 120 with other diagnoses. Only the markers t-PA and NT-proBNP were associated positively and significantly (p < 0.01) with a diagnosis of TIA or stroke. The FAST had a sensitivity of 82% (95% CI 78-87) and specificity of 38% (95% CI 29-46) for the diagnosis of TIA or stroke. No biomarker individually improved the sensitivity or specificity of the FAST. A model containing the FAST, age, systolic blood pressure, NT-proBNP and t-PA had a better sensitivity (88%, p < 0.006) and a better specificity (48%, p = 0.04) than the FAST test alone.</p> <p><b>Conclusions:</b> No single blood marker improved the diagnostic performance of a validated clinical stroke scale. Panels of biomarkers may marginally improve diagnosis, but their practicability is uncertain, and requires further study.</p&gt

Associations of Parent–Child Anxious and Depressive Symptoms When a Caregiver Has a History of Depression

We examined the associations between parent and child anxious and depressive symptoms controlling for co-occurring symptoms in both. One hundred and four families participated, including 131 9–15 year old children considered at risk for anxiety and/or depression due to a history of depression in a parent. Parents and children completed questionnaires assessing depressive and anxious symptoms. Linear Mixed Models analyses controlling for the alternate parent and child symptoms indicated that both parent and child depressive symptoms and parent and child anxious symptoms were positively associated. Parental depressive symptoms were not positively associated with child anxious symptoms, and parental anxious symptoms were not positively associated with child depressive symptoms. The findings provide evidence for positive specific links between parent and child development of same-syndrome, but not cross-syndrome, symptoms when a caregiver has a history of depression