Improving the competence and confidence of pulmonary and critical care medicine fellows in performing a cricothyrotomy

Clinical opportunities to practice or perform a cricothyrotomy are limited. We developed an evidence-based cricothyrotomy course following the 4-phase lesson plan for simulation that provides pulmonary and critical care medicine fellows with demonstrations, practice, and feedback to increase their confidence and competence.Survey results demonstrated an improvement in perceived confidence (p<0.005) and competence (p<0.002) following this educational intervention.  Fellows also achieved significant improvement in knowledge (p<0.003) and performance in two cricothyrotomy techniques (Seldinger and MacIntyre) (p<0.004).It is important that we provide fellows with practice opportunities that can be used to develop and maintain proficiency, particularly in low frequency events

Novel roles for JNK1 in metabolism

Activation of stress-kinase signaling has recently been recognized as an important pathophysiological mechanism in the development of diet-induced obesity, type 2 diabetes mellitus and other aging-related pathologies. Here, c-Jun N-terminal Kinase (JNK) 1 knockout mice have been shown to exhibit protection from diet-induced obesity, glucose intolerance, and insulin resistance. Nonetheless, the tissue-specific role of JNK1-activation in the development of the metabolic syndrome has been poorly defined so far. Recently, it was demonstrated that JNK1 signaling plays a crucial role in the central nervous system (CNS) and in the pituitary to control systemic glucose and lipid metabolism partially through regulation of hormones involved in growth and energy expenditure

Global Diversification and IPO Returns

A large number of newly listed firms have significant involvement in international business activity. In this paper, we examine the effect of international business activity on the pricing of initial public offerings (IPOs), post-IPO performance, and survival. In a large sample of U.S. IPOs over 1981–2012, we find that firms with exports and/or foreign sales prior to going public have significantly lower underpricing than firms without international business activity. Furthermore, firms with international business activity significantly outperform purely domestic IPO firms over 3- and 5-year periods after going public and have a significantly higher survival rate. Overall, we provide strong evidence that global diversification has an economically significant effect on the valuation and subsequent performance of firms going public

Ariel - Volume 1 Number 3

Copyright 1969 Arie

Myeloid Cell-Restricted Insulin Receptor Deficiency Protects Against Obesity-Induced Inflammation and Systemic Insulin Resistance

A major component of obesity-related insulin resistance is the establishment of a chronic inflammatory state with invasion of white adipose tissue by mononuclear cells. This results in the release of pro-inflammatory cytokines, which in turn leads to insulin resistance in target tissues such as skeletal muscle and liver. To determine the role of insulin action in macrophages and monocytes in obesity-associated insulin resistance, we conditionally inactivated the insulin receptor (IR) gene in myeloid lineage cells in mice (IRΔmyel-mice). While these animals exhibit unaltered glucose metabolism on a normal diet, they are protected from the development of obesity-associated insulin resistance upon high fat feeding. Euglycemic, hyperinsulinemic clamp studies demonstrate that this results from decreased basal hepatic glucose production and from increased insulin-stimulated glucose disposal in skeletal muscle. Furthermore, IRΔmyel-mice exhibit decreased concentrations of circulating tumor necrosis factor (TNF) α and thus reduced c-Jun N-terminal kinase (JNK) activity in skeletal muscle upon high fat feeding, reflecting a dramatic reduction of the chronic and systemic low-grade inflammatory state associated with obesity. This is paralleled by a reduced accumulation of macrophages in white adipose tissue due to a pronounced impairment of matrix metalloproteinase (MMP) 9 expression and activity in these cells. These data indicate that insulin action in myeloid cells plays an unexpected, critical role in the regulation of macrophage invasion into white adipose tissue and in the development of obesity-associated insulin resistance

A Question of Choice

Women's reproductive rights, reproductive health, and constitutional privacy rights in the United States are addressed in light of the contemporary onslaught of the Christian Right. The misuse of State power by fundamentalist social forces in America is critiqued. The article also briefly reviews the question of State control over women's bodies

The first 110,593 COVID-19 patients hospitalised in Lombardy: a regionwide analysis of case characteristics, risk factors and clinical outcomes

Objectives: To describe the monthly distribution of COVID-19 hospitalisations, deaths and case-fatality rates (CFR) in Lombardy (Italy) throughout 2020. Methods: We analysed de-identified hospitalisation data comprising all COVID-19-related admissions from 1 February 2020 to 31 December 2020. The overall survival (OS) from time of first hospitalisation was estimated using the Kaplan-Meier method. We estimated monthly CFRs and performed Cox regression models to measure the effects of potential predictors on OS. Results: Hospitalisation and death peaks occurred in March and November 2020. Patients aged ≥70 years had an up to 180 times higher risk of dying compared to younger patients [70–80: HR 58.10 (39.14–86.22); 80–90: 106.68 (71.01–160.27); ≥90: 180.96 (118.80–275.64)]. Risk of death was higher in patients with one or more comorbidities [1: HR 1.27 (95% CI 1.20–1.35); 2: 1.44 (1.33–1.55); ≥3: 1.73 (1.58–1.90)] and in those with specific conditions (hypertension, diabetes). Conclusion: Our data sheds light on the Italian pandemic scenario, uncovering mechanisms and gaps at regional health system level and, on a larger scale, adding to the body of knowledge needed to inform effective health service planning, delivery, and preparedness in times of crisis

Development of Tract-Specific White Matter Pathways During Early Reading Development in At-Risk Children and Typical Controls

Developmental dyslexia is a neurodevelopmental disorder with a strong genetic basis. Previous studies observed white matter alterations in the left posterior brain regions in adults and school-age children with dyslexia. However, no study yet has examined the development of tract-specific white matter pathways from the pre-reading to the fluent reading stage in children at familial risk for dyslexia (FHD+) versus controls (FHD−). This study examined whitematter integrity at pre-reading, beginning, and fluent reading stages cross-sectionally (n = 78) and longitudinally (n = 45) using an automated fiber-tract quantification method. Our findings depict white matter alterations and atypical lateralization of the arcuate fasciculus at the pre-reading stage in FHD+ versus FHD− children. Moreover, we demonstrate faster white matter development in subsequent good versus poor readers and a positive association between white matter maturation and reading development using a longitudinal design. Additionally, the combination of white matter maturation, familial risk, and psychometric measures best predicted later reading abilities. Furthermore, within FHD+ children, subsequent good readers exhibited faster white matter development in the right superior longitudinal fasciculus compared with subsequent poor readers, suggesting a compensatory mechanism. Overall, our findings highlight the importance of white matter pathway maturation in the development of typical and atypical reading skills

Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

Trial designThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13-17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0 mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial registrationClinicalTrials.gov NCT00701415