Lack of effect of the human GM-CSF analog E21R on the survival of primary human acute myeloid leukemia cells

The granulocyte-macrophage colony-stimulating factor (GM-CSF) analog E21R binds to the GM-CSF receptor complex with low affinity and acts as a competitive antagonist. In addition, it has been reported to be a potent direct activator of apoptosis in primary human acute myeloid leukemia (AML) cells. We have confirmed the ability of E21R to neutralize the biologic effects of GM-CSF and investigated its activity on primary AML blasts. We find that it failed to induce cell death in blast cells from 23 separate AML cases treated in vitro at concentrations of E21R up to 30 µg/mL. Significant cell death resulted in all cases after incubation with cytosine arabinoside. The lack of effect of E21R on AML blasts was unlikely to be due to an absence of functional GM-CSF receptors because 13 cases demonstrated an increase in cell number with the addition of exogenous GM-CSF. These results do not support the use of E21R for the treatment of AML

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Secondary hyperparathyroidism (SHPT) is a common complication of CKD and is part of the chronic kidney disease-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality, thus SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between pre-dialysis CKD and dialysis patients which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options

Hemichorea as a presentation of acute rheumatic fever: a case report

Chorea is a major manifestation of acute RF and is the only evidence of RF in approximately 20% of cases. We report on a 15-year-old boy who presented with transient right side involuntary jerky movements, apical systolic murmur, sinus bradycardia, arthralgia, elevated antistreptolysin O titer and ESR, who was diagnosed with acute rheumatic fever and improved with haloperidol, prednisolone, digoxin, aspirin and furosemide and was given benzathine penicillin prophylaxis for future RF. Patient is faring well in follow up visits. We present our case because of its rarity

Tax farming redux: experimental evidence on performance pay for tax collectors

Performance pay for tax collectors has the potential to raise revenues, but might come at a cost if it increases the bargaining power of tax collectors vis-à-vis taxpayers. We report the first large-scale field experiment on these issues, where we experimentally allocated 482 property tax units in Punjab, Pakistan, into one of three performance pay schemes or a control. After two years, incentivized units had 9.4 log points higher revenue than controls, which translates to a 46% higher growth rate. The scheme that rewarded purely on revenue did best, increasing revenue by 12.9 log points (64% higher growth rate), with little penalty for customer satisfaction and assessment accuracy compared to the two other schemes that explicitly also rewarded these dimensions. The revenue gains accrue from a small number of properties becoming taxed at their true value, which is substantially more than they had been taxed at previously. The majority of properties in incentivized areas in fact pay no more taxes, but instead report higher bribes. The results are consistent with a collusive setting in which performance pay increases collectors’ bargaining power over taxpayers, who have to either pay higher bribes to avoid being reassessed or pay substantially higher taxes if collusion breaks down

Aligning daily activities with personality: towards a recommender system for improving wellbeing

Recommender Systems have not been explored to a great extentfor improving health and subjective wellbeing. Recent advances inmobile technologies and user modelling present the opportunityfor delivering such systems, however the key issue is understand-ing the drivers of subjective wellbeing at an individual level. Inthis paper we propose a novel approach for deriving personalizedactivity recommendations to improve subjective wellbeing by maxi-mizing the congruence between activities and personality traits. Toevaluate the model, we leveraged a rich dataset collected in a smart-phone study, which contains three weeks of daily activity probes,the Big-Five personality questionnaire and subjective wellbeingsurveys. We show that the model correctly infers a range of activ-ities that are ’good’ or ’bad’ (i.e. that are positively or negativelyrelated to subjective wellbeing) for a given user and that the derivedrecommendations greatly match outcomes in the real-world