Intraosseous (IO) vs Intravenous (IV) Vascular Access for Out of Hospital Cardiac Arrest.

Over 300,000 Americans every year experience an out-of-hospital cardiac arrest (OHCA) (Benjamin EJ 2019). Of these 300,000+ patients only 10.6% of them survive to hospital discharge. Advanced Cardiac Life Support (ACLS) has been suggested to improve survival following an OHCA (Neumar, Otto et al. 2010). Current ACLS guidelines recommend obtaining vascular access, however, offer little suggestion as to which type of access device should be used. It is our belief that using an Intraosseous vascular access device will lead to shorter time to medication delivery and increased rates of return of spontaneous circulation (ROSC) compared to Intravenous vascular access. We conducted a retrospective chart review study with patients from Detroit Receiving Hospital and Sinai- Grace Hospital from January 1st, 2014 to December 31st, 2015. Over 3000 OHCA patients were used for this study. Only adult OHCA patients with vascular access obtained in the Emergency Department were included in the study for data analysis. Chart review was conducted by research personnel who underwent a standardized training procedure. The forms of vascular access, time to first ACLS medication, and return of ROSC were the main parameters recorded. Data analysis was conducted using IBM SPSS- Statistics (2015) or a similar statistical software. The initial data shows that there is no statistical difference in ROSC rates when comparing IO lines to IV lines. We are currently in the process of analyzing the data on time to first medication delivery between IO and IV lines. We intend to publish this study in peer reviewed journals, and to present the results at local, regional, and national presentations. It is our intention that this study will serve as a pilot study for future randomized control trials comparing different vascular access devices for OHCA patients in the Emergency Department. References: Benjamin EJ, M. P., Alonso A, & Bittencourt MS. (2019). Heart disease and stroke Statistics—2019 update: A report from the American Heart Association. . Neumar, R. W., et al. (2010). Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 122(18 Suppl 3): S729-767

The cancer angiogenesis co-culture assay:In vitro quantification of the angiogenic potential of tumoroids

The treatment response to anti-angiogenic agents varies among cancer patients and predictive biomarkers are needed to identify patients with resistant cancer or guide the choice of anti-angiogenic treatment. We present “the Cancer Angiogenesis Co-Culture (CACC) assay”, an in vitro Functional Precision Medicine assay which enables the study of tumouroid induced angiogenesis. This assay can quantify the ability of a patient-derived tumouroid to induce vascularization by measuring the induction of tube formation in a co-culture of vascular cells and tumoroids established from the primary colorectal tumour or a metastasis. Furthermore, the assay can quantify the sensitivity of patient-derived tumoroids to anti-angiogenic therapies. We observed that tube formation increased in a dose-dependent manner upon treatment with the pro-angiogenic factor vascular endothelial growth factor A (VEGF-A). When investigating the angiogenic potential of tumoroids from 12 patients we found that 9 tumoroid cultures induced a significant increase in tube formation compared to controls without tumoroids. In these 9 angiogenic tumoroid cultures the tube formation could be abolished by treatment with one or more of the investigated anti-angiogenic agents. The 3 non-angiogenic tumoroid cultures secreted VEGF-A but we observed no correlation between the amount of tube formation and tumoroid-secreted VEGF-A. Our data suggests that the CACC assay recapitulates the complexity of tumour angiogenesis, and when clinically verified, could prove a valuable tool to quantify sensitivity towards different anti-angiogenic agents

Increased bactericidal activity of colistin on <i>Pseudomonas aeruginosa </i>biofilms in anaerobic conditions

Tolerance towards antibiotics of Pseudomonas aeruginosa biofilms is recognized as a major cause of therapeutic failure of chronic lung infection in cystic fibrosis (CF) patients. This lung infection is characterized by antibiotic-tolerant biofilms in mucus with zones of O(2) depletion mainly due to polymorphonuclear leukocytic activity. In contrast to the main types of bactericidal antibiotics, it has not been possible to establish an association between the bactericidal effects of colistin and the production of detectable levels of OH ˙ on several strains of planktonic P. aeruginosa. Therefore, we propose that production of OH ˙ may not contribute significantly to the bactericidal activity of colistin on P. aeruginosa biofilm. Thus, we investigated the effect of colistin treatment on biofilm of wild-type PAO1, a catalase-deficient mutant (ΔkatA) and a colistin-resistant CF isolate cultured in microtiter plates in normoxic- or anoxic atmosphere with 1 mM nitrate. The killing of bacteria during colistin treatment was measured by CFU counts, and the OH⋅ formation was measured by 3(′)-(p-hydroxylphenyl fluorescein) fluorescein (HPF) fluorescence. Validation of the assay was done by hydrogen peroxide treatment. OH⋅ formation was undetectable in aerobic PAO1 biofilms during 3 h of colistin treatment. Interestingly, we demonstrate increased susceptibility of P. aeruginosa biofilms towards colistin during anaerobic conditions. In fact, the maximum enhancement of killing by anaerobic conditions exceeded 2 logs using 4 mg L(−1) of colistin compared to killing at aerobic conditions

AI (r)evolution -- where are we heading? Thoughts about the future of music and sound technologies in the era of deep learning

Artificial Intelligence (AI) technologies such as deep learning are evolving very quickly bringing many changes to our everyday lives. To explore the future impact and potential of AI in the field of music and sound technologies a doctoral day was held between Queen Mary University of London (QMUL, UK) and Sciences et Technologies de la Musique et du Son (STMS, France). Prompt questions about current trends in AI and music were generated by academics from QMUL and STMS. Students from the two institutions then debated these questions. This report presents a summary of the student debates on the topics of: Data, Impact, and the Environment; Responsible Innovation and Creative Practice; Creativity and Bias; and From Tools to the Singularity. The students represent the future generation of AI and music researchers. The academics represent the incumbent establishment. The student debates reported here capture visions, dreams, concerns, uncertainties, and contentious issues for the future of AI and music as the establishment is rightfully challenged by the next generation

A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease

n/

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis