Tectonic evolution of the Karakoram metamorphic complex (NW Himalayas) reflected in the 3D structures of spiral garnets: Insights from X-ray computed micro-tomography

We thank Pentti Hölttä and Syed Zahid Shah for many useful discussions. We thank the referees, F. George and an anonymous reviewer, for their constructive comments.Spiral garnet porphyroblasts are known to record lengthy periods of deformation and metamorphism by preserving single or multiple FIAs (Foliation Intersection Axis) formed normal to tectonic shortening directions. Thanks to technological advances in X-ray computed micro-tomography (XCMT), FIAs can now be readily determined in relatively large samples in contrast to previous methods that require the preparation of a set of radial vertical and horizontal thin sections of samples. XCMT scanning not only alleviates tedious thin section based procedures but also illuminates the complete internal architecture of a rock sample allowing three-dimensional (3D) quantitative shape analysis of an individual porphyroblast as well as precise measurement of FIAs. We applied the technique to a sample from the Hunza Valley in the Karakoram metamorphic complex (KMC), NW Himalayas, containing numerous garnet porphyroblasts with spiral-shaped inclusion trails. The XCMT imaging reveals an E-Wtrending FIA within the sample, which is consistent with orthogonal N-S collision of the India-Kohistan Island Arc with Asia. Garnet long axes (X-GT) have variable plunges that define a broad sub-vertical maximumand a small sub-horizontalmaximum. The X-GT principle maxima lie at N-090 and N-120. Smaller maxima lie at N-020 and N- 340. Geometric relationships between X-GT axes and FIA orientation in the sample suggest that porphyroblast shapes are controlled by the geometry of the lens-shaped microlithons in which they tend to nucleate and grow. The orientation of inclusion trails and matrix foliations in the sample are correlated with three discrete tectono-metamorphic events that respectively produced andalusite, sillimanite and kyanite in the KMC. Late staurolite growth in the sample reveals howthe rocks extruded to the surface via a significant role of roll-on tectonics, which can be correlated with the Central Himalayas

Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.</p> <p>Methods/Design</p> <p>The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register (NTR1303)</p

Neuronal networks provide rapid neuroprotection against spreading toxicity

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients. Here, using hippocampal neurons (DIV 15-20) cultured in microfluidic devices in order to deliver a localized excitotoxic insult, we replicate secondary spreading toxicity and demonstrate that this process is driven by GluN2B receptors. In addition to the modeling of spreading toxicity, this approach has uncovered a previously unknown, fast acting, GluN2A-dependent neuroprotective signaling mechanism. This mechanism utilizes the innate capacity of surrounding neuronal networks to provide protection against both forms of spreading neuronal toxicity, synaptic hyperactivity and direct glutamate excitotoxicity. Importantly, network neuroprotection against spreading toxicity can be effectively stimulated after an excitotoxic insult has been delivered, and may identify a new therapeutic window to limit brain damage

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

Item does not contain fulltextBACKGROUND: Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS: We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS: Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2.05, 95% CI 1.18-3.56; p=0.0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION: Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING: The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

internationalization strategies and policies in second tier higher education institutions

This study addresses the major objectives and challenges in the internationalization processes of second-tier higher education institutions. We use the examples of universities of applied sciences in the Netherlands, academic colleges in Israel, and community colleges in Canada to offer a global perspective regarding the internationalization efforts in these types of institutions. Through comprehensive comparative analysis of secondary sources, we identify the trends taking place within these types of higher education institutions in these countries. We find that second-tier institutions tend not to have solidified for themselves tailored internationalization approaches and strategies that are uniquely fitting to their own missions, aims and student populations. This oversight creates a situation whereby such institutions, despite their culturally diverse student populations and the promise they hold to create a unique niche within internationalization discourse, fail to utilize the potential inherent in targeted internationalization strategies

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Study protocol of EMPOWER : A Cluster Randomized trial of a multimodal eHealth intervention for promoting mental health in the workplace following a Stepped Wedge Trial Design

Objective: This article describes the EMPOWER study, a controlled trial aiming to determine the effectiveness and cost-effectiveness of an eHealth intervention to prevent common health problems and reduce presenteeism and absenteeism in the workplace. Intervention: The EMPOWER intervention spans universal, secondary and tertiary prevention and consists of an eHealth platform delivered via a website and a smartphone app designed to guide employees throughout different modules according to their specific profiles. Design: A stepped-wedge cluster randomized trial will be implemented in four countries (Finland, Poland, Spain and UK) with employees from small and medium enterprises (SMEs) and public agencies. Companies will be randomly allocated in one of three groups with different times at which the intervention is implemented. The intervention will last 7 weeks. Employees will answer several questionnaires at baseline, pre- and post-intervention and follow-up. Outcome measures: The main outcome is presenteeism. Secondary outcomes include depression, anxiety, insomnia, stress levels, wellbeing and absenteeism. Analyses will be conducted at the individual level using the intention-to-treat approach and mixed models. Additional analyses will evaluate the intervention effects according to gender, country or type of company. Cost-effectiveness and cost-utility analyses [based on the use of quality-adjusted life-years (QALYS)] will consider a societal, employers’ and employees’ perspective

Design and development of a digital intervention for workplace stress and mental health (EMPOWER)

Purpose: We describe the design and development of the European Platform to Promote health and wellbeing in the workplace (EMPOWER) digital intervention that provides an integrative user programme meeting the needs of employees and employers in addressing work stress. Results: A user-centred design process was followed from January 2020 until November 2021. A tailored algorithm was developed to provide support at the individual employee level and the company level. Each element of the digital intervention was developed in English and then translated in Spanish, English, Polish and Finnish. The digital intervention consists of a website and a mobile application (app) that provides algorithm-based personalised content after assessing a user's somatic and psychological symptoms, work functioning, and psychosocial risk factors for work stress. It has a public section and an employer portal that provides recommendations to reduce psychosocial risks in their company based upon clustered input from employees. Usability testing was conducted and showed high ease of use and completion of tasks by participants. Conclusion: The EMPOWER digital intervention is a tailored multimodal intervention addressing wellbeing, work stress, mental and physical health problems, and work productivity. This will be used in a planned RCT in four countries to evaluate its effectiveness