Robots and the skill premium : an automation-based explanation of wage inequality

We analyze the effects of automation on the wages of high-skilled and low- skilled workers and thereby on the evolution of wage inequality. Our model explains the simultaneous presence of i) increasing per capita GDP, ii) de-clining real wages of low-skilled workers, and iii) an increasing skill-premium. These developments are consistent with the experience in the United States over the past decades and have the potential to contribute to the explanation of the rise in overall incomeinequality that we have observed since the 1980s

Overlapping Presence of Macroamylasemia and Hyperamylasemia in Acute Pancreatitis

This is an Open Access article distributed under the terms of the Creative Commons Attributio

A possible role for Ca2+/calmodulin-dependent protein kinase IV during pancreatic acinar stimulus–secretion coupling

AbstractCa2+/calmodulin-dependent protein kinases (CaMKs) are important intracellular mediators in the mediation of stimulus–secretion coupling and excitation–contraction coupling in a wide variety of cell types. We attempted to identify and characterize the functional roles of CaMK in mediating pancreatic enzyme secretion. Immunoprecipitation and immunoblotting studies using a CaMKII or CaMKIV antibody showed that rat pancreatic acini expressed both CaMKII and CaMKIV. Phosphotransferase activities of CaMKs were measured by a radioenzyme assay (REA) using autocamtide II, peptide γ and myosin P-light chain as substrates. Although CaMKII and CaMKIV use autocamtide II as a substrate, peptide γ is more efficiently phosphorylated by CaMKIV than by CaMKII. Intact acini were stimulated with cholecystokinin (CCK)-8, carbachol (CCh) and the high-affinity CCK-A receptor agonist, CCK-OPE, and the cell lysates were used for REA. CCK-8, CCh and CCK-OPE caused a concentration-dependent increase in CaMKs activities. When autocamtide II was used, maximal increases were 1.5–1.8-fold over basal (20.2±2.0 pmol/min/mg protein), with peaks occurring at 20 min after cell stimulation. In separate studies that used peptide γ, CCK-8, CCh and CCK-OPE dose-dependently increased CaMKIV activities. Maximal increases were 1.5–2.4-fold over basal (30.7±3.2 pmol/min/mg protein) with peaks occurring at 20 min after cell stimulation. Peak increases after cell stimulation induced by peptide γ were 1.8–2.8-fold higher than those induced by autocamtide II. CCK-8, CCh and CCK-OPE also significantly increased phosphotransferase activities of myosin light chain kinase (MLCK) substrate (basal: 4.4±0.7 pmol/min/mg protein). However, maximal increases induced by MLCK substrate were less than 10% of those occurring in peptide γ. Characteristics of the phosphotransferase activity were also different between autocamtide II and peptide γ. When autocamtide II was used, elimination of medium Ca2+ in either cell lysates or intact cells resulted in a significant decrease in the activity, whereas it had no or little effect when peptide γ was used. This suggests that Ca2+ influx from the extracellular space is not fully required for CaMKIV activity and Ca2+ is not a prerequisite for phosphotransferase activity once CaMKIV is activated by either intracellular Ca2+ release or intracellular Ca2+ oscillations. The specific CaMKII inhibitor KN-62 (50 μM) had no effect on the CaMKIV activity and pancreatic enzyme secretion elicited by CCK-8, CCh and CCK-OPE. The specific MLCK inhibitor, ML-9 (10 μM), also did not inhibit CCK-8-stimulated pancreatic amylase secretion. In contrast, wide spectrum CaMK inhibitors, K-252a (1 μM) and KT5926 (3 μM), significantly inhibited CaMKIV activities and enzyme secretion evoked by secretagogues. Thus, CaMKIV appears to be an important intracellular mediator during stimulus–secretion coupling of rat pancreatic acinar cells

Effect of the Frequency of Self-Monitoring Blood Glucose in Patients with Type 2 Diabetes Treated with Oral Antidiabetic Drugs—A Multi-Centre, Randomized Controlled Trial

OBJECTIVE: Recommendations on the frequency of self-monitoring of blood glucose (SMBG) vary widely among physicians treating patients with type 2 diabetes (T2D). Aim of this study was to investigate two testing regimen of SMBG in patients with stable metabolic control. RESEARCH DESIGN AND METHODS: Patients with T2D treated with oral antidiabetic drugs were randomized to two groups: either one SMBG (low) or four SMBG (high) per week. Subjects were followed up after 3, 6 and 12 months. Primary outcome parameter was the change in HbA1c between baseline and 6 months. Primary outcome criterion was tested by a one-sided t- test for non- inferiority. Secondary outcome parameters were safety, compliance and HbA1c at 3 and 12 months. RESULTS: There were no differences in the 202 subjects for demographic and sociodemographic parameters and drug treatment. HbA(1)c (%) at baseline was similar in both groups (7.2+/-1.4 vs. 7.2+/-1.0). Non- inferiority was demonstrated for the low group (p = 0.0022) with a difference from baseline to 6 months of 0.24 in the low and of 0.16 in the high group. Compliance with the testing regimen was 82-90% in both groups. There were no statistical significant differences for compliance, HbA(1)c at 3 and 12 months and serious adverse events (SAE). CONCLUSION: One SMBG per week is as sufficient and safe as four SMBG per week to maintain HbA(1)c in non-insulin treated T2D close to metabolic target. The results of this study are in contrast to current international consensus guidelines. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN79164268

Use of a basal-plus insulin regimen in persons with type 2 diabetes stratified by age and body mass index: A pooled analysis of four clinical trials

AIMS: To evaluate the efficacy and safety of adding a single bolus dose of insulin glulisine to basal insulin ('basal-plus') in persons with type 2 diabetes. METHODS: Data from patients with poor glycemic control on oral antihyperglycemic drugs who were initiated on a 'basal-plus' regimen for up to 6 months were pooled from four randomized, multicenter studies. Glycated hemoglobin (HbA1c), fasting blood glucose, postprandial glucose (PPG), insulin dose and demographics were measured at baseline and end of study. RESULTS: 711 patients with a mean age of 59.9 years and a mean duration of diabetes of 11.0 years were included in the analysis population. A 'basal-plus' regimen was associated with significant decreases in HbA1c and PPG at 6 months, an increase in glargine and glulisine doses and small, but statistically significant, changes in body weight and BMI in all patient subsets. The proportion of patients with HbA1c<7% also increased in all populations studied, while the prevalence of severe hypoglycemia was low and did not significantly differ across patient groups. CONCLUSIONS: These results suggest that the use of 'basal-plus' can achieve a good therapeutic response with a low risk of hypoglycemia and weight gain, regardless of a patient's age or BMI. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved

A progressive increase in cardiovascular risk assessed by coronary angiography in non-diabetic patients at sub-diabetic glucose levels

<p>Abstract</p> <p>Objective</p> <p>Diabetes mellitus type 2 (DM2) is a risk factor for coronary heart disease (CHD). While there is a clear correlation of fasting blood glucose (FBG) and 2 h post-challenge blood glucose values (2h-BG) with microvascular complications, the risk for CHD conferred by glucose dysregulation antecedent to DM2 is less clear. Therefore, we investigated associations of FBG and 2h-BG values with the prevalence of CHD assessed by coronary angiography as the most sensitive diagnostic tool.</p> <p>Research Design and Methods</p> <p>Coronary angiography was performed in 1394 patients without known DM. Capillary blood glucose was analyzed before and 2 h after an oral glucose tolerance test. Associations between FBG as well as 2h-BG levels and the risk for CHD were assessed by logistic regression analysis.</p> <p>Results</p> <p>1064 (75%) of patients were diagnosed with CHD. 204 (15%) were diagnosed with so far unknown DM2, 274 (20%) with isolated impaired fasting glucose (IFG), 188 (13%) with isolated impaired glucose tolerance (IGT) and 282 (20%) with both, IGT and IFG. We found a continuous increase in the risk for CHD with fasting and post-challenge blood glucose values even in the subdiabetic range. This correlation did however not suggest clear cut-off values. The increase in risk for CHD reached statistical significance at FBG levels of > 120 mg/dl (Odds Ratio of 2.7 [1.3-5.6] and 2h-BG levels > 140 mg/dl (141-160 mg/dl OR 1.8 [1.1-2.9], which was however lost after adjusting for age, sex and BMI.</p> <p>Conclusions</p> <p>In our study population we found a continuous increased risk for CHD at fasting and 2h-BG levels in the sub-diabetic glucose range, but no clear cut-off values for cardiovascular risk.</p

Relation of global longitudinal strain to left ventricular geometry in aortic valve stenosis

Background: In patients with aortic stenosis (AS), increased afterload induces changes in left ventricular (LV) geometry to preserve a normal ejection fraction (EF). Nevertheless, myocardial dysfunction may occur in spite of a normal EF. Global longitudinal strain (GLS) analysis can detect subtle contractile dysfunction at a pre-clinical stage. The aim of our study was to assess LV function deteriorations with GLS analysis and the association with geometric changes in patients with AS and normal EF. Methods: Forty four patients with moderate to severe AS and 40 controls were enrolled. All patients underwent echocardiography, including two-dimensional strain imaging. The relative wall thickness and LV muscle mass measurements were performed with magnetic resonance imaging and patients were subdivided into four groups: Group 1 with normal LV, Group 2 with concentric remodeling, Group 3 with eccentric hypertrophy, and Group 4 with concentric hypertrophy. Results: The total group of patients with AS showed a GLS of -15.3 &#177; 3.6% while the control group reached -18.9 &#177; 3.2% (p < 0.001). GLS was lower in the hypertrophy Groups 3 and 4 compared to Groups 1 and 2 (12.9 &#177; 3.4% vs 17.2 &#177; 2.5%, p < 0.05, respectively). Splitting the patients into Groups 1 to 4, the GLS was -17.2 &#177; 2.4%, -17.2 &#177; 2.7%, -12.4 &#177; 3.8% and -13.1 &#177; 3.3, respectively (p = 0.002). Conclusions: In subjects with AS, lower GLS is related to LV hypertrophy, but not to the presence of concentric remodeling. Assessment of GLS can identify subtle contractile dysfunction independent of a preserved EF, and might be useful in identifying patients at high risk for the transition from compensatory to pathological remodeling. (Cardiol J 2011; 18, 2: 151-156

Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD.</p> <p>Methods</p> <p>We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines.</p> <p>Results</p> <p>IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001).</p> <p>Conclusions</p> <p>Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.</p

Correlations between atazanavir Ctrough and hyperbilirubinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hyperbilirubinemia is a common side effect of the antiretroviral agent atazanavir but is generally reversible upon discontinuation of treatment. We used therapeutic drug monitoring to investigate the occurrence of hyperbilirubinemia in a 49-year-old Hispanic man infected with HIV, following an overdose of ritonavir in ritonavir-boosted atazanavir therapy.</p> <p>Case presentation</p> <p>A 49-year-old Hispanic man with HIV who had received several highly active antiretroviral therapy regimens over a number of years including atazanavir-containing regimens, was diagnosed with hyperbilirubinemia. An inappropriate doubling of ritonavir boosting resulted in a high atazanavir C_troughand an initial rise in bilirubin plasma levels. Bilirubin levels later decreased, probably as a consequence of enzyme induction, while atazanavir plasma concentrations remained elevated.</p> <p>Conclusion</p> <p>This article describes an occurrence of hyperbilirubinemia in a man infected with HIV and supports the importance of therapeutic drug monitoring in investigations of hyperbilirubinemia among patients receiving antiretroviral agents. That the patient tolerated exceptionally high atazanavir levels further strengthens the tolerability profile of this drug.</p