Location and Level of Etk Expression in Neurons Are Associated with Varied Severity of Traumatic Brain Injury

Much recent research effort in traumatic brain injury (TBI) has been devoted to the discovery of a reliable biomarker correlating with severity of injury. Currently, no consensus has been reached regarding a representative marker for traumatic brain injury. In this study, we explored the potential of epithelial/endothelial tyrosine kinase (Etk) as a novel marker for TBI.TBI was induced in Sprague Dawley (SD) rats by controlled cortical impact. Brain tissue samples were analyzed by Western blot, Q-PCR, and immunofluorescence staining using various markers including glial fibrillary acidic protein, and epithelial/endothelial tyrosine kinase (Etk). Results show increased Etk expression with increased number and severity of impacts. Expression increased 2.36 to 7-fold relative to trauma severity. Significant upregulation of Etk appeared at 1 hour after injury. The expression level of Etk was inversely correlated with distance from injury site. Etk and trauma/inflammation related markers increased post-TBI, while other tyrosine kinases did not.The observed correlation between Etk level and the number of impacts, the severity of impact, and the time course after impact, as well as its inverse correlation with distance away from injury site, support the potential of Etk as a possible indicator of trauma severity

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Failure analysis in ITO-free all-solution processed organic solar cells

\u3cp\u3eIn this paper we discuss a problem-solving methodology and present guidance for troubleshooting defects in ITO-free all-solution processed organic solar cells with an inverted cell architecture. A systematic approach for identifying the main causes of failures in devices is presented. Comprehensive analysis of the identified failure mechanisms allowed us to propose practical solutions for further avoiding and eliminating failures in all-solution processed organic solar cells. Implementation of the proposed solutions has significantly improved the yield and quality of all-solution processed organic solar cells.\u3c/p\u3

Digitally printed photovoltaic devices with increasing stack complexity

\u3cp\u3eDigital printing of organic photovoltaic devices is presented as a viable option for the creation of increasingly complex device structures. Fully printed organic tandem junction devices were made that show a perfect summation of the open circuit voltages of the subcells. These results show the feasibility of complete digitally printed device stacks providing product designers with unprecedented freedom of design for integration of a photovoltaic functionality in new products.\u3c/p\u3

Digitally printed photovoltaic devices with increasing stack complexity

Solution processing of OPVs on industrial scale brings some challenges, such as finding alternative, non-chlorinated solvents and using roll-to-roll compatible processes. Here we present a fully inkjet printed tandem OPV device, which consists of up to 9 sequentially inkjet printed layers. The inkjet printed layers are made without chlorinated solvents using an industrial scale printhead, making the processing industrial viable.\u3cbr/\u3eThe main challenge for inkjet printing this tandem structure was to find a good way to print the recombination contact consisting of a closed PEDOT:PSS layer from a water based solution onto a hydrophobic P3HT:PCBM layer and on top of that a ZnO layer. Previously it was shown by our group that ZnO can be inkjet printed on a PEDOT:PSS layer, however, when modifying (commercial) PEDOT:PSS formulations the resulting surface energy of this PEDOT:PSS layer changes and hence the printability of ZnO on top of the PEDOT:PSS is different. Careful optimization of the full recombination contact was done and tandem devices were successfully inkjet printed.\u3cbr/\u3eThe voltage of the inkjet printed tandem we present here is the sum of the voltages of the subcells, which shows that there are no voltage losses over the recombination contact. The efficiency of the inkjet printed tandems was higher than the efficiencies of the respective single junction devices. These results show that inkjet printing is a promising technique to up-scale the production of tandem OPVs and commercialization is one step closer

Association of suicidal behavior with exposure to suicide and suicide attempt: A systematic review and multilevel meta-analysis

BACKGROUND: Exposure to suicidal behavior may be associated with increased risk of suicide, suicide attempt, and suicidal ideation and is a significant public health problem. However, evidence to date has not reliably distinguished between exposure to suicide versus suicide attempt, nor whether the risk differs across suicide-related outcomes, which have markedly different public health implications. Our aim therefore was to quantitatively assess the independent risk associated with exposure to suicide and suicide attempt on suicide, suicide attempt, and suicidal ideation outcomes and to identify moderators of this risk using multilevel meta-analysis. METHODS AND FINDINGS: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, ASSIA, Sociological Abstracts, IBSS, and Social Services Abstracts from inception to 19 November 2019. Eligible studies included comparative data on prior exposure to suicide, suicide attempt, or suicidal behavior (composite measure-suicide or suicide attempt) and the outcomes of suicide, suicide attempt, and suicidal ideation in relatives, friends, and acquaintances. Dichotomous events or odds ratios (ORs) of suicide, suicide attempt, and suicidal ideation were analyzed using multilevel meta-analyses to accommodate the non-independence of effect sizes. We assessed study quality using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Thirty-four independent studies that presented 71 effect sizes (exposure to suicide: k = 42, from 22 independent studies; exposure to suicide attempt: k = 19, from 13 independent studies; exposure to suicidal behavior (composite): k = 10, from 5 independent studies) encompassing 13,923,029 individuals were eligible. Exposure to suicide was associated with increased odds of suicide (11 studies, N = 13,464,582; OR = 3.23, 95% CI = 2.32 to 4.51, P < 0.001) and suicide attempt (10 studies, N = 121,836; OR = 2.91, 95% CI = 2.01 to 4.23, P < 0.001). However, no evidence of an association was observed for suicidal ideation outcomes (2 studies, N = 43,354; OR = 1.85, 95% CI = 0.97 to 3.51, P = 0.06). Exposure to suicide attempt was associated with increased odds of suicide attempt (10 studies, N = 341,793; OR = 3.53, 95% CI = 2.63 to 4.73, P < 0.001), but not suicide death (3 studies, N = 723; OR = 1.64, 95% CI = 0.90 to 2.98, P = 0.11). By contrast, exposure to suicidal behavior (composite) was associated with increased odds of suicide (4 studies, N = 1,479; OR = 3.83, 95% CI = 2.38 to 6.17, P < 0.001) but not suicide attempt (1 study, N = 666; OR = 1.10, 95% CI = 0.69 to 1.76, P = 0.90), a finding that was inconsistent with the separate analyses of exposure to suicide and suicide attempt. Key limitations of this study include fair study quality and the possibility of unmeasured confounders influencing the findings. The review has been prospectively registered with PROSPERO (CRD42018104629). CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that prior exposure to suicide and prior exposure to suicide attempt in the general population are associated with increased odds of subsequent suicidal behavior, but these exposures do not incur uniform risk across the full range of suicide-related outcomes. Therefore, future studies should refrain from combining these exposures into single composite measures of exposure to suicidal behavior. Finally, future studies should consider designing interventions that target suicide-related outcomes in those exposed to suicide and that include efforts to mitigate the adverse effects of exposure to suicide attempt on subsequent suicide attempt outcomes.status: publishe

Adjusting for confounding by indication in observational studies: a case study in traumatic brain injury

Maryse C Cnossen,1 Thomas A van Essen,2,3 Iris E Ceyisakar,1 Suzanne Polinder,1 Teuntje M Andriessen,4 Joukje van der Naalt,5 Iain Haitsma,6 Janneke Horn,7 Gaby Franschman,8 Pieter E Vos,9 Wilco C Peul,2,3 David K Menon,10 Andrew IR Maas,11 Ewout W Steyerberg,1,12 Hester F Lingsma1 1Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 2Neurosurgical Cooperative Holland, Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands; 4Department of Psychology, RIVAS Healthcare Group, Gorinchem, the Netherlands; 5Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands; 6Department of Neurosurgery, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 7Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Department of Anesthesiology, VU University Medical Center Amsterdam, Amsterdam, the Netherlands; 9Department of Neurology, Slingeland Hospital, Doetinchem, the Netherlands; 10Division of Anaesthesia, University of Cambridge/Addenbrooke&rsquo;s Hospital, Cambridge, UK; 11Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium; 12Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands Introduction: Observational studies of interventions are at risk for confounding by indication. The objective of the current study was to define the circumstances for the validity of methods to adjust for confounding by indication in observational studies. Patients and methods: We performed post hoc analyses of data prospectively collected from three European and North American traumatic brain injury studies including 1,725 patients. The effects of three interventions (intracranial pressure [ICP] monitoring, intracranial operation and primary referral) were estimated in a proportional odds regression model with the Glasgow Outcome Scale as ordinal outcome variable. Three analytical methods were compared: classical covariate adjustment, propensity score matching and instrumental variable (IV) analysis in which the percentage exposed to an intervention in each hospital was added as an independent variable, together with a random intercept for each hospital. In addition, a simulation study was performed in which the effect of a hypothetical beneficial intervention (OR 1.65) was simulated for scenarios with and without unmeasured confounders. Results: For all three interventions, covariate adjustment and propensity score matching resulted in negative estimates of the treatment effect (OR ranging from 0.80 to 0.92), whereas the IV approach indicated that both ICP monitoring and intracranial operation might be beneficial (OR per 10% change 1.17, 95% CI 1.01&ndash;1.42 and 1.42, 95% CI 0.95&ndash;1.97). In our simulation study, we found that covariate adjustment and propensity score matching resulted in an invalid estimate of the treatment effect in case of unmeasured confounders (OR ranging from 0.90 to 1.03). The IV approach provided an estimate in the similar direction as the simulated effect (OR per 10% change 1.04&ndash;1.05) but was statistically inefficient. Conclusion: The effect estimation of interventions in observational studies strongly depends on the analytical method used. When unobserved confounding and practice variation are expected in observational multicenter studies, IV analysis should be considered. Keywords: confounding, observational studies, traumatic brain injury, instrumental variable analysis, comparative effectiveness researc