Tackling Crises Together? – An Econometric Analysis of Charitable Crowdfunding During the COVID-19 Pandemic

Crowdfunding platforms enable individuals or groups to appeal to the public to support a variety of ventures or campaigns. Whilst the majority of campaigns raise funds for private causes, some of the issues for which help is being sought have arisen as a direct consequence of world events and crises. Nevertheless, the research on charitable crowdfunding has largely ignored this connection. We use the COVID-19 pandemic, and related public health policies, to explore the impact of the global crisis on donation behavior on the donation-based crowdfunding platform GoFundMe. By using a quasi-experimental research design, we find that after the introduction of stay-at-home orders, campaigns in U.S. states with such measures experienced a significant decline in the number of donors and amounts donated, which is more pronounced for crisis-related than for non-crisis-related campaigns. Our findings contribute to the literature by providing novel insights on crowdfunding behaviors in times of societal crisis

GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium

Growth arrest-specific 1 (GAS1) acts as a co-receptor to patched 1, promoting sonic hedgehog (SHH) signaling in the developing nervous system. GAS1 mutations in humans and animal models result in forebrain and craniofacial malformations, defects ascribed to a function for GAS1 in SHH signaling during early neurulation. Here, we confirm loss of SHH activity in the forebrain neuroepithelium in GAS1-deficient mice and in induced pluripotent stem cell-derived cell models of human neuroepithelial differentiation. However, our studies document that this defect can be attributed, at least in part, to a novel role for GAS1 in facilitating NOTCH signaling, which is essential to sustain a persistent SHH activity domain in the forebrain neuroepithelium. GAS1 directly binds NOTCH1, enhancing ligand-induced processing of the NOTCH1 intracellular domain, which drives NOTCH pathway activity in the developing forebrain. Our findings identify a unique role for GAS1 in integrating NOTCH and SHH signal reception in neuroepithelial cells, and they suggest that loss of GAS1-dependent NOTCH1 activation contributes to forebrain malformations in individuals carrying GAS1 mutations

Penumbral Rescue by Normobaric O=O Administration in Patients with Ischemic Stroke and Target Mismatch ProFile (PROOF): Study Protocol of a Phase IIb Trial.

RATIONALE Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. AIMS PROOF investigates the use of normobaric oxygen therapy (NBO) within six hours of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior circulation occlusion. METHODS AND DESIGN Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. STUDY OUTCOMES Primary outcome is ischemic core growth (mL) from baseline to 24 hours (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 hours, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers are conducted. SAMPLE SIZE Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. DISCUSSION By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 hours on follow-up imaging reduces potential bias due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. TRIAL REGISTRATIONS ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31