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With more individuals forcibly displaced than any time since the Second World War, forced displacement has emerged as one of the defining political and humanitarian issues of the twenty-first century. In response to the changing nature of displacement, shortcomings of the humanitarian sector, and several ideological shifts that have taken place over the past 20 years, innovation has been embraced as a method to generate new breakthrough solutions for forced displacement. This article takes stock of innovation in forced displacement and charts a path forward for innovation in the sector. We articulate a vision for what forced displacement response should look like in 20 years, detailing an innovation agenda at the individual level, country level, and sector level. Grounded in our lessons learned from leading innovation at the International Rescue Committee, a large humanitarian non-governmental organization (NGO), we outline a set of strategies the sector should adopt to increase the quantity and quality of new innovations, improve the mechanisms to identify cost-effective innovations, and enhance the paths to scale for these innovations.

Myogenic reactivity in resistance arteries/arterioles in response to changing intraluminal pressure is a key physiological mechanism for the regulation of blood pressure and flow. Although IP3-mediated intracellular Ca2+ release is known to contribute to the myogenic response, a lack of selective pharmacological agents to target the predominant IP3R1 Ca2+ release channel has prevented detailed investigation of this key mechanism. Mutations in the IP3R1 known to produce either loss-of-function (LOF) or gain-of-function (GOF) phenotypes lead to cerebellar ataxia in humans, yet the effect of these mutations on the cardiovascular system remains unclear. Here, we employed a novel genetic knock-in mouse model with a single point mutation in the S6 helix of IP3R1 that confers either a LOF (D2594A) or GOF (D2594K) phenotype. In endothelium-denuded posterior cerebral arteries of 3-4 month old WT mice, myogenic vasoconstriction was evident at ≥40 mmHg, maximal at ~120 mmHg, and began to decline at >120 mmHg (n=9). In contrast, myogenic constriction was initiated at higher pressures (≥50 mmHg) and was less robust in arteries of heterozygous IP3R1 LOF mice (n=11). In GOF arteries (n=10), myogenic tone developed at a lower pressure (~20 mmHg), was maximal at ~80 mmHg, and declined at >90 mmHg. Interestingly, pressure-induced Ca2+ elevations were similar in Fura-2 loaded arteries from WT, LOF and GOF mice. Using high sensitivity western blotting, we observed a similar pressure-dependent increase in phosphorylated myosin regulatory light chain (LC20) and myosin phosphatase targeting subunit (MYPT1) at 10, 40, 80 and 120 mmHg in arteries from WT, LOF and GOF mice (n=5 each). Although phospho-MYPT1-T855 content increased with intraluminal pressure in WT and LOF arteries, it did not change in vessels of GOF mice. Elevation of intraluminal pressure (i.e., from 10 to 60 or 120 mmHg) significantly decreased G-actin content in WT arteries, did not affect G-actin content in LOF vessels, and caused a biphasic effect in GOF arteries. Stabilizing the actin cytoskeleton with 0.1 mM jasplakinolide normalized myogenic reactivity in LOF arteries and left-shifted myogenic responsiveness in WT vessels; a minimal effect was observed in GOF arteries. Both jasplakinolide and the actin depolymerizing agent latrunculin B (2 mM) inhibited myogenic tone development at intraluminal pressures > 40-60 mmHg. Taken together, these data demonstrate that genetic modification of IP3R1-mediated Ca2+ mobilization affects the myogenic response of cerebral arteries to intraluminal pressure, possibly by affecting the dynamics of the actin cytoskeleton. Functionally, the observed vascular impairments may contribute to neurological dysfunction in patients with LOF and GOF IP3R1 mutations. Funding has been provided by the Canadian Institutes of Health Research: MOP-97988 (WCC), MOP-142467 (APB), PJT-173352 (SRWC) and PJT-155963 (APB, WCC, GRG and SRWC). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Genetic variations in CD2-associated protein (CD2AP) predispose to Alzheimer’s disease (AD) but the underlying mechanisms remain unknown. Here, we show that a cerebrovascular loss of CD2AP in AD is associated with cognitive decline and genetic downregulation of CD2AP in brain microvessels impairs memory function in two distinct mouse models. The memory deficits are linked to reduced cerebral blood flow during resting state and altered neurovascular coupling in pial vessels, arterioles and capillaries. In brain endothelial cells, CD2AP regulates the levels and signaling of ApoE receptor 2 (ApoER2). Activation of the CD2AP-ApoER2 pathway with Reelin glycoprotein mitigates the toxic effects of Aβ on capillary blood flow and on vasomotion of arterioles depleted of CD2AP. We propose that deregulation of CD2AP perturbs distinct segments of the brain vascular network, and harnessing the biology of specific brain vessel types may offer refined therapeutic strategies for the treatment of AD.

A 60-year-old male presented with complaints of a non-healing wound on his right shin. Initial angiography showed a 100% occlusion of the right superficial femoral artery thought to be thrombotic in nature; he was treated with percutaneous transluminal angioplasty and stenting. Three weeks later, he presented with continuing symptoms of claudication. Angiography revealed stent fracture. Careful review of his prior angiogram was consistent with adventitial cystic disease of the popliteal artery as the cause of the popliteal artery occlusion. He was then referred for femoral-popliteal bypass.

This previously unpublished letter brings to light the friendship between George Whitefield and John Collett Ryland, the Baptist pastor and educator. Details of this relationship and of Ryland's su...

International audience; The understanding of the physical processes controlling water fluxes from hillslope aquifers to surface waters is critically needed for predicting stream discharge and establishing sustainable water resources management strategies. Two major hypotheses are currently being debated: the first considers that climate, stream network morphology and topography have a first-order control on groundwater flow and stream recession. Thus the prediction of stream baseflow can be approximated by considering idealized homogeneous groundwater reservoirs with effective properties. The second hypothesis suggests that the structural heterogeneity of the landscape (lithological variations, geological discontinuities, spatial distribution of topographic and tectonic stresses) might significantly control the partitioning of water within the landscape, and in turn impact how streamflow recession behaves.In this contribution we provide a comprehensive analysis of stream discharge and geomorphological databases across various geological domains distributed throughout the globe in order to identify the main factors that might influence recession constants at baseflow. A novel computational approach for single recession analysis revealed that recession constants might strongly deviate from what is predicted from idealized theories, with power law recession constants ranging from 1.5 to more than 10. A correlation analysis allows us to identify the control of key features of the landscape on groundwater storage and streamflow recession constants, with depth to bedrock, lithology and maturity - i.e. degree of weathering and fracturing - of the landscape being the main drivers. We tested these observations through a numerical modelling framework which allowed us to quantify the variability of streamflow recession behaviors raising from the drainage of hillslopes with different structural and geometrical properties. We identify the respective roles of hydraulic conductivity contrasts between the upper and lower compartments, the depth of the shallower compartment and the steepness of the slope on streamflow recession parameters. We finally discuss the implications of these findings in establishing future strategies for the improvement of groundwater storage and stream discharge predictions.

Large wood (LW) plays an important role in river ecosystems, but LW-laden floods may cause serious damage to human lives and property. The relationship between precipitation patterns and variations in LW distribution and export at the watershed scale is poorly understood. To explore these linkages, we examined differences in LW distribution as a function of channel morphologies in six watersheds located in southern and northern Japan and analysed the impacts of different precipitation patterns on the fluvial export of LW from river catchments. In southern Japan, intense rainfalls caused by typhoons or localized torrential downpours initiate landslides and debris flows that introduce massive amounts of LW into channels. Gravel bars formed by frequent flood events are widely prevalent, and the LW temporarily stored on these bars is frequently moved and/or broken into smaller pieces by floods. In these systems fluvial export of LW is supply-limited, with smaller accumulations and shorter residence times than in northern Japan. Conversely, in northern Japan, where typhoons and torrential downpours rarely occur, LW is mostly recruited by bank erosion, tree mortality and windthrow into channels, rather than by landslides and debris flows. Recruited pieces accumulate in log jams on valley floors, particularly on floodplains supporting mature forests, resulting in larger accumulations and longer residence times. In these watersheds fluvial export of LW is transport-limited, and the pieces gradually decompose during long-term storage as log jams. Copyright (C) 2015 John Wiley & Sons, Ltd.