The impact of venture capital on governance decisions in collaborations with start-ups

This article addresses solutions for contractual hazards in the formation and operation of collaborations with start-ups. We suggest that venture capitalists may serve as a mechanism to mitigate contractual hazards and act as a substitute for equity sharing in joint ventures. This article is to our knowledge the first to address the impact of venture capital (VC) on governance decisions for start-ups. We analyze 5405 bilateral collaborations from the SDC database for the period 2009-2014, and find that VC-backed firms are less likely to share equity in collaborations

Risk factors for lobar and non-lobar intracerebral hemorrhage in patients with vascular disease

Introduction Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. Methods In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. Results During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH. Conclusion This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH

Intracerebral haemorrhage — mechanisms, diagnosis and prospects for treatment and prevention

Intracerebral haemorrhage (ICH) is a devastating condition associated with high mortality and substantial residual disability among survivors. Effective treatments for the acute stages of ICH are limited. However, promising findings from randomized trials of therapeutic strategies, including acute care bundles that target anticoagulation therapies, blood pressure control and other physiological parameters, and trials of minimally invasive neurosurgical procedures have led to renewed optimism that patient outcomes can be improved. Currently ongoing areas of research for acute treatment include anti-inflammatory and haemostatic treatments. The implementation of effective secondary prevention strategies requires an understanding of the aetiology of ICH, which involves vascular and brain parenchymal imaging; the use of neuroimaging markers of cerebral small vessel disease improves classification with prognostic relevance. Other data underline the importance of preventing not only recurrent ICH but also ischaemic stroke and cardiovascular events in survivors of ICH. Ongoing and planned randomized controlled trials will assess the efficacy of prevention strategies, including antiplatelet agents, oral anticoagulants or left atrial appendage occlusion (in patients with concomitant atrial fibrillation), and optimal management of long-term blood pressure and statin use. Together, these advances herald a new era of improved understanding and effective interventions to reduce the burden of ICH

Diagnostic accuracy of myocardial perfusion imaging in patients evaluated for kidney transplantation:A systematic review and meta-analysis

BACKGROUND: Cardiovascular disease is the most common cause of death after kidney transplantation. Coronary artery disease (CAD) assessment is therefore mandatory in patients evaluated for transplantation. We aimed to assess the diagnostic accuracy for CAD of single-photon emission computed tomography (SPECT) compared to the standards invasive coronary angiography (ICA) and coronary computed tomography angiography (CCTA) in patients evaluated for kidney transplantation. METHODS: We performed a systematic literature search in PubMed, EMBASE, Web of Science, OvidSP (Medline), The Cochrane Library and Google Scholar. Studies investigating the diagnostic accuracy of myocardial perfusion imaging (MPI) SPECT in patients evaluated for kidney transplantation were retrieved. After a risk of bias assessment using QUADAS-2, a meta-analysis was conducted. RESULTS: Out of 1459 records, 13 MPI SPECT studies were included in the meta-analysis with a total of 1245 MPI SPECT scans. There were no studies available with CCTA as reference. Pooled sensitivity of MPI SPECT for CAD was 0.66 (95% CI 0.53 to 0.77), pooled specificity was 0.75 (95% CI 0.63 to 0.84) and the area under the curve (AUC) was 0.76. Positive likelihood ratio was 2.50 (95% CI 1.78 to 3.51) and negative likelihood ratio was 0.41 (95% CI 0.28 to 0.61). Pooled positive predictive value was 64.9% and pooled negative predictive value was 74.1%. Significant heterogeneity existed across the included studies. CONCLUSIONS: MPI SPECT had a moderate diagnostic accuracy in patients evaluated for kidney transplantation, with a high rate of false-negative findings. The use of an anatomical gold standard against a functional imaging test in the included studies is however suboptimal. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12350-021-02621-x

Influence of Polymorphisms in Innate Immunity Genes on Susceptibility to Invasive Aspergillosis after Stem Cell Transplantation

The innate immune system plays a pivotal role in the primary defence against invasive fungal infection. Genetic variation in genes that regulate this response, initiated by pulmonary macrophages, may influence susceptibility to invasive aspergillosis in patients at risk. We investigated in a clinical setting whether common polymorphisms in Toll-like receptor (TLR) and cytokine genes involved in macrophage regulation are associated with susceptibility to invasive aspergillosis. Forty-four allogeneic stem cell transplantation recipients diagnosed with probable or proven IA according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group, were enrolled. The control group consisted of 64 allogeneic stem cell transplantation recipients without invasive aspergillosis. The TLR4 1063A>G single nucleotide polymorphism was associated with invasive aspergillosis when present in donors of allogeneic stem cell transplantation recipients (unadjusted OR 3.77 95%CI 1.08–13.2, p = 0.03). In a multivariate analysis, adjusted for occurrence of graft-versus-host-disease, Cytomegalovirus serostatus and duration of neutropenia, paired presence of the TLR4 1063A>G and IFNG 874T>A single nucleotide polymorphisms showed a trend towards increased susceptibility to invasive aspergillosis (p = 0.04). These findings point to the relevant immunological pathway involved in resistance to invasive aspergillosis and warrant further study of the effects of TLR and cytokine polymorphisms and their interaction, which may occur on different levels of the complex biological interplay between the immunocompromised host and Aspergillus sp

International Survey on Mechanical Ventilation During Extracorporeal Membrane Oxygenation

The optimal ventilation strategy for patients on extracorporeal membrane oxygenation (ECMO) remains uncertain. This survey reports current mechanical ventilation strategies adopted by ECMO centers worldwide. An international, multicenter, cross-sectional survey was conducted anonymously through an internet-based tool. Participants from North America, Europe, Asia, and Oceania were recruited from the extracorporeal life support organization (ELSO) directory. Responses were received from 48 adult ECMO centers (response rate 10.6%). Half of these had dedicated ventilation protocols for ECMO support. Pressure-controlled ventilation was the preferred initial ventilation mode for both venovenous ECMO (VV-ECMO) (60%) and venoarterial ECMO (VA-ECMO) (34%). In VV-ECMO, the primary goal was lung rest (93%), with rescue therapies commonly employed, especially neuromuscular blockade (93%) and prone positioning (74%). Spontaneous ventilation was typically introduced after signs of pulmonary recovery, with few centers using it as the initial mode (7%). A quarter of centers stopped sedation within 3 days after ECMO initiation. Ventilation strategies during VA-ECMO focused less on lung-protective goals and transitioned to spontaneous ventilation earlier. Ventilation strategies during ECMO support differ considerably. Controlled ventilation is predominantly used initially to provide lung rest, often facilitated by sedation and neuromuscular blockade. Few centers apply "awake ECMO" early during ECMO support, some utilizing partial neuromuscular blockade.</p

Simultaneous Protein Quantitation and Glycosylation Profiling of Antigen-Specific Immunoglobulin G1 in Large Clinical Studies

Antibodies have a key role in the immune system, making their characterization essential to biomedical, biopharmaceutical, and clinical research questions. Antibody effector functions are mainly controlled by quantity, subclass, and Fc glycosylation. We describe an integrated method to measure these three critical dimensions simultaneously. The subclass-specific immunoglobulin G (IgG) Fc glycosylation analysis combines immunosorbance with glycopeptide-centered LC-MS detection. For integrated IgG1-specific quantitation, a commercial, stable isotope labeled IgG1 protein standard was spiked into the immunosorbent eluates. Robust quantitation was achieved, relying on a combination of a proteotypic peptide and the most abundant glycopeptides, generated through proteolytic cleavage from a mixture of natural IgG1 and the recombinant IgG1 standard. Method performance was demonstrated in a large coronavirus vaccination cohort at a throughput of 100 samples/day. LC-MS-derived, anti-SARS-CoV-2 spike protein IgG1 concentrations ranged from 100 to 10000 ng/mL and correlated well with a clinically relevant immunoassay. Technical variation was 200 times lower than biological variation; intermediate precision was 44%. In conclusion, we present a method capable of robustly and simultaneously assessing quantity, subclass, and Fc glycosylation of antigen-specific IgG in large clinical studies. This method will facilitate a broader understanding of immune responses, especially the important interplay among the three dimensions