Training school teachers to promote mental and social well-being in low and middle income countries : lessons to facilitate scale-up from a participatory action research trial of youth first in India

Mental and social wellbeing (MSWB) promotion programs could improve mental health and other outcomes for youth in Low and Middle Income Countries (LMICs). Unfortunately, few such programs have progressed to scale-up and few studies have detailed processes and considerations that could facilitate doing so. This study begins to fill these gaps, describing key findings from training and supporting government middle school teachers to deliver the Youth First Resilience Curriculum, a MSWB promotion program, in Bihar, India. We conducted a Participatory Action Research trial of the resilience curriculum among 792 middle school youth and 55 teachers at 15 government schools. Participant-observations, exit interviews, and group discussions were conducted and analyzed via multiple rounds of coding to generate thematic findings. A number of schools showed relatively high levels of interest, session reliability and fidelity, student interaction and teacher facilitative abilities, but there was great variation within the sample. Three leverage points emerged to facilitate future scale-up: factors for successful site assessment and program initiation, supporting teacher success via interest and motivation, and responding to varied teacher skill levels. These points represent critical focus areas for practitioners and policy-makers as more MSWB promotion programs begin to scale in LMICs.peer-reviewe

Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests.This work has received funding from the European Community's Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no 278612 (BIOHYBRID). This study was also funded by European Union's FP7 Programme under grant agreement no REGPOT-CT2012-316331-POLARIS.The authors thank the chitosan raw material provided by Altakitin S.A., (Lisboa, Portugal). We are further thankful to Silke Fischer, Natascha Heidrich, Kerstin Kuhlemann, Jennifer Metzen, Hildegard Streich and Maike Wesemann (all from the Institute of Neuroanatomy, Hannover Medical School) for their technical support

Modeling intracranial aneurysm stability and growth: An integrative mechanobiological framework for clinical cases

We present a novel patient-specific fluid-solid-growth framework to model the mechanobiological state of clinically detected intracranial aneurysms (IAs) and their evolution. The artery and IA sac are modeled as thick-walled, non-linear elastic fiber-reinforced composites. We represent the undulation distribution of collagen fibers: the adventitia of the healthy artery is modeled as a protective sheath whereas the aneurysm sac is modeled to bear load within physiological range of pressures. Initially, we assume the detected IA is stable and then consider two flow-related mechanisms to drive enlargement: (1) low wall shear stress; (2) dysfunctional endothelium which is associated with regions of high oscillatory flow. Localized collagen degradation and remodelling gives rise to formation of secondary blebs on the aneurysm dome. Restabilization of blebs is achieved by remodelling of the homeostatic collagen fiber stretch distribution. This integrative mechanobiological modelling workflow provides a step towards a personalized risk-assessment and treatment of clinically detected IAs

The effect of aneurysm geometry on the intra-aneurysmal flow condition

Various anatomical parameters affect on intra-aneurysmal hemodynamics. Nevertheless, how the shapes of real patient aneurysms affect on their intra-aneurysmal hemodynamics remains unanswered. Quantitative computational fluid dynamics simulation was conducted using eight patients’ angiograms of internal carotid artery–ophthalmic artery aneurysms. The mean size of the intracranial aneurysms was 11.5 mm (range 5.8 to 19.9 mm). Intra-aneurysmal blood flow velocity and wall shear stress (WSS) were collected from three measurement planes in each aneurysm dome. The correlation coefficients (r) were obtained between hemodynamic values (flow velocity and WSS) and the following anatomical parameters: averaged dimension of aneurysm dome, the largest aneurysm dome dimension, aspect ratio, and dome–neck ratio. Negative linear correlations were observed between the averaged dimension of aneurysm dome and intra-aneurysmal flow velocity (r = −0.735) and also WSS (r = −0.736). The largest dome diameter showed a negative correlation with intra-aneurysmal flow velocity (r = −0.731) and WSS (r = −0.496). The aspect ratio demonstrated a weak negative correlation with the intra-aneurysmal flow velocity (r = −0.381) and WSS (r = −0.501). A clear negative correlation was seen between the intra-aneurysmal flow velocity and the dome–neck ratio (r = −0.708). A weak negative correlation is observed between the intra-aneurysmal WSS and the dome–neck ratio (r = −0.392). The aneurysm dome size showed a negative linear correlation with intra-aneurysmal flow velocity and WSS. Wide-necked aneurysm geometry was associated with faster intra-aneurysmal flow velocity

Direct estimation of wall shear stress from aneurysmal morphology: A statistical approach

Computational fluid dynamics (CFD) is a valuable tool for studying vascular diseases, but requires long computational time. To alleviate this issue, we propose a statistical framework to predict the aneurysmal wall shear stress patterns directly from the aneurysm shape. A database of 38 complex intracranial aneurysm shapes is used to generate aneurysm morphologies and CFD simulations. The shapes and wall shear stresses are then converted to clouds of hybrid points containing both types of information. These are subsequently used to train a joint statistical model implementing a mixture of principal component analyzers. Given a new aneurysmal shape, the trained joint model is firstly collapsed to a shape only model and used to initialize the missing shear stress values. The estimated hybrid point set is further refined by projection to the joint model space. We demonstrate that our predicted patterns can achieve significant similarities to the CFD-based results

Uncertainty quantification of wall shear stress in intracranial aneurysms using a data-driven statistical model of systemic blood flow variability

Adverse wall shear stress (WSS) patterns are known to play a key role in the localisation, formation, and progression of intracranial aneurysms (IAs). Com- plex region-specific and time-varying aneurysmal WSS patterns depend both on vascular morphology as well as on variable systemic ow conditions. Com- putational uid dynamics (CFD) has been proposed for characterising WSS patterns in IAs; however, CFD simulations often rely on deterministic bound- ary conditions that are not representative of the actual variations in blood ow. We develop a data-driven statistical model of internal carotid artery (ICA) ow, which is used to generate a virtual population of waveforms used as inlet bound- ary conditions in CFD simulations. This allows the statistics of the resulting aneurysmal WSS distributions to be computed. It is observed that ICA wave- form variations have limited in uence on the time-averaged WSS (TAWSS) on the IA surface. In contrast, in regions where the ow is locally highly multidi- rectional, WSS directionality and harmonic content are strongly affected by the ICA ow waveform. As a consequence, we argue that the effect of blood ow variability should be explicitly considered in CFD-based IA rupture assessment to prevent confounding the conclusions

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone

Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo

Intracranial aneurysms are associated with disturbed velocity patterns, and chronic inflammation, but the relevance for these findings are currently unknown. Here, we show that (disturbed) shear stress induced by vortices is a sufficient condition to activate the endothelial NF-kB pathway, possibly through a mechanism of mechanosensor de-activation. We provide evidence for this statement through in-vitro live cell imaging of NF-kB in HUVECs exposed to different flow conditions, stochastic modelling of flow induced NF-kB activation and induction of disturbed flow in mouse carotid arteries. Finally, CFD and immunofluorescence on human intracranial aneurysms showed a correlation similar to the mouse vessels, suggesting that disturbed shear stress may lead to sustained NF-kB activation thereby offering an explanation for the close association between disturbed flow and intracranial aneurysms