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[ILLUSTRATION OMITTED] Working 9 to 5 is one way to make a living, but many employees are trying to find the right balance between career and family life. More companies […]

[ILLUSTRATION OMITTED] Many airlines across the United States have undergone numerous operational changes over the past several years transforming the world of travel. Alaska air travel has been at the […]

[ILLUSTRATION OMITTED] Businesses setting down roots often look for locations where they most likely will prosper. For years, Alaska has been rich soil for many companies and small businesses because […]

Ana Gonzalez Quintero and Casey Allen are two of the newest qualified team members at Hinxton Crocus Early Years Centre. In 2023, the duo both completed their journeys on the Bright Horizons Apprenticeship Programme and are now enjoying their roles as Level 3 Early Years Educator practitioners. Here they share their journey into the sector and experiences of the programme.

To examine the association between cardiorespiratory fitness (CRF) at baseline and cardiovascular disease (CVD) risk in 6- to 10-year-olds (cross-sectional) and 2 years later (8- to 12-year-olds [longitudinal]) and whether changes with age in CRF are associated with CVD risk in children aged 8 to 12 years.

[ILLUSTRATION OMITTED] Alaska has many great companies helping build the future for Alaskans. One of them is Alaska Industrial Hardware (AIH), which will mark its 50th anniversary. With its half-century […]

[ILLUSTRATION OMITTED] A new entrepreneur might have a great idea for a product or service, but if this person doesn't have the self-esteem to make it work, it won't. You […]

In this research we propose a physical measure of resource efficiency, based on exergy, which combines energy and material flows in a single dimensionless metric, bounded by 0 and 1. The inclusion of materials in the efficiency metric makes it possible to compare a wide range of industrial devices and processes, and even different sectors, using a consistent framework. Resource efficiencies for steel-making processes were computed as an example and were found to range from 10.0% in sinter plants to72.1% in coke ovens. A unified resource efficiency measure helps identify the drivers of resource consumption and reveal opportunities to reduce carbon emissions.

The age-old debate, 'Are leaders born or made? is one that has been discussed for years. If you were to ask Donna Boltz, she would probably say some experienced leaders [...]

The pathogenesis of neurodegenerative diseases involves altered activity of proteolytic systems and accumulation of protein aggregates. Autophagy is an intracellular process in which damaged organelles and long-lived proteins are degraded and recycled for maintaining normal cellular homeostasis. Disruption of autophagic activity in neurons leads to modify the cellular homeostasis, causing deficient elimination of abnormal and toxic protein aggregates that promotes cellular stress and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons to clear abnormal protein aggregates and survive. This review aims to give an overview of some of the main modulators of autophagy that are currently being studied as possible alternatives in the search of therapies that slow the progression of neurodegenerative diseases, which are incurable to date.

Introduction:Myocarditis is a rare but highly morbid complication of immune-checkpoint inhibitors (ICI) use. Improved methods for detection and risk stratification are needed. Cytotoxic chemotherapy associates with reduced global circumferential strain (GCS) but no data is available on the utility of GCS in ICI myocarditis.Hypothesis:We hypothesized that GCS by echocardiography would be reduced in ICI myocarditis and the magnitude of reduction would have prognostic implications.Methods:In this retrospective cohort, GCS from 75 patients with ICI myocarditis (cases) and 49 ICI treated patients without myocarditis (controls) was compared. Pre-ICI GCS values were available for 10 cases and 39 controls. Measurements were performed by a reader blinded to group and time (TomTec, Germany). Major adverse cardiac event was defined as a composite of cardiogenic shock, cardiac arrest, complete heart block, and cardiac death.Results:Cases and controls had similar age (66±15 vs. 63±12 years; p=0.19), sex (male: 55% vs. 66%; p=0.22) and cancer type (p=0.08). Pre-ICI GCS values were lower in cases (n=10) than in controls (n=39) (-21.7±2.0 vs. -23.5±2.9, p=0.04), but within normal range. Overall, 56% (n=42) of cases had left ventricular ejection fraction (LVEF) >50% at presentation. The GCS was lower in cases than in controls (-17.5±4.2 vs. -23.5±3.0, p<0.001) in the entire cohort and in both preserved (-19.7±3.8 vs. -23.6±3.0, p<0.001) and reduced EF (-14.6±2.7 vs. -20.9±2.3, p<0.001) strata. Over a median follow-up of 30 days, 28 events occurred. An absolute GCS value < the median (17.1%) was associated with an increased rate of events (HR: 4.9, 95% CI: 1.6-15.0, p=0.005, Figure), adjusted for age and LVEF. The association was also noted when GCS is treated as continuous (HR: 1.18, 95% CI: 1.03-1.35, p=0.02).Conclusions:Global circumferential strain is lower in patients with ICI-myocarditis and the magnitude of the reduction in GCS has prognostic significance.

Introduction:Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis.Hypothesis:We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications.Methods:Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death.Results:Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of >50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p<0.01). This lower GRS value was noted in patients with both preserved EF (31.7±5.5 vs. 47.0±7.6, p<0.001) and reduced EF (24.7±6.1 vs. 49.2±4.7, p<0.005). In total, 28 events occurred during a median follow-up of 30 days. In survival analysis, a GRS < the median (29.4%) was associated with an increased rate of events (HR: 3.92, 95% CI: 1.42-10.78, p=0.008) adjusted for age and LVEF. The association between GRS and events was also noted when the variable is treated as continuous adjusted for age and LVEF (HR: 1.07, 95% CI: 1.001-1.15 p=0.04).Conclusions:Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.

Behçet's disease (BD) is a chronic inflammatory disease of unknown etiology associated with an increased risk of venous and arterial thrombosis. To date, no studies for haemostasis have been conducted in this population by rotational thromboelastometry and thrombin generation test. These methods appear to be more sensitive and specific than routine coagulation tests in detecting defects of the coagulation system and could provide new elements for better understanding the mechanisms involved in the hypercoagulable state observed in BD patients. On this basis, this work aims to study haemostasis in patients with BD by rotational thromboelastometry (ROTEM ®) and thrombin generation test (CAT).Twenty-six patients with BD were included. Ages were between 25–86 years (mean ± SD: 48.60 ± 15.66 years) and 73% were female. Eight patients had active disease at the time of enrollment and 6 had a history of thrombosis. Control group included 20 healthy individuals aged between 28–55 years (42.85 ± 9.02 years) and 65% were female.Rotational thromboelastometry was performed in whole blood with ROTEM® coagulation analyzer (Pentapharm, Munich, Germany) at INTEM condition (activation of coagulation mainly throughout intrinsic pathway). Samples were allowed to rest 1 hour at room temperature and heated for 4 minutes at 37 ° C immediately before testing.Thrombin generation was measured in platelet-free plasma by the method of Hemker (Calibrated Automated Thrombography, CAT). Activation was performed with a final concentration of 4 mM of phospholipids and 1 pM of tissue factor which favored the activation of coagulation mainly throughout intrinsic pathway.Normal distribution for continuous variables was assessed with the Shapiro-Wilk testComparisons of quantitative variables were made with non-paired Student's t-test or Mann-Whitney's U test as appropriate.Values of thromboelastometry parameters were increased in samples from BD patients. The higher clot consistency at 5 and 10 minutes (p=0.0452 and p=0.0179 respectively), and the pronounced maximal clot firmness (p=0.0064) suggest that platelet function may be altered in our patient cohort. Moreover, values higher than control ones for a angle (p=0.0266), maximum clot formation velocity (p=0.0454) and area under the curve at 5 and 10 minutes (p=0.0206 and p=0.0220 respectively) point to an increased thrombin generation in BD patients. In order to verify this hypothesis, thrombin generation was evaluated in samples from these patients. CAT experiments showed that BD patients had an increased endogenous thrombin potential (p = 0.0251) and reached higher maximum levels of thrombin (peak height, p = 0.0119) than controls.To determine if haemostatic profile in BD patients evaluated by rotational thromboelastometry and CAT correlates with disease activity, Spearman's rank correlation coefficient was calculated. There was a significant but mild correlation between disease activity and area under the curve at 5 minutes (r=0.3818, p=0.0494) and the maximal clot firmness (r=0.3978, p= 0.0399) (thromboelastometry parameters) and the peak height (r=0.4615, p=0.0251) (CAT parameter).Rotational thromboelastometry at INTEM condition and thrombin generation test confirmed that there is a hypercoagulable state in Behcet's disease. Procoagulant/anticoagulant protein equilibrium and platelet function may be altered in this pathology as indicated by several parameter measured by both tests.No relevant conflicts of interest to declare.