The Economics of Suicide

On April 8th 1994 Kurt Cobain, the lead singer of Nirvana, was found dead in his Seattle home of an apparent shotgun wound to the head and with three times the lethal amount of heroin in his system. A note lay at the scene. The verdict was suicide. Others are sceptical.’ (from www.deathofkurtcobain.com) In the pall of gloom surrounding Michael Jackson’s recent death when we read this extract from a site dedicated to Kurt Cobain, a number of questions struck us as being interesting. Why do famous celebrities commit suicide? Could the reasons be monetary, social or some other phenomenon? Why would such renowned personalities give up an apparent life of luxury? In furthering our understanding of these issues it strikes us as pertinent to ask whether we can ever view suicide from the perspective of an economist. Can we assess human behaviour pertaining to suicide using the ration al science of economics or are we treading on unknown territory in psychiatry instead? Consider a quote by the famous economist Gary Becker from his book The Economic Approach to Human Behaviour

Sensitive and Specific Fluorescent Probes for Functional Analysis of the Three Major Types of Mammalian ABC Transporters

An underlying mechanism for multi drug resistance (MDR) is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins. ABC transporters also determine the general fate and effect of pharmaceutical agents in the body. The three major types of ABC transporters are MDR1 (P-gp, P-glycoprotein, ABCB1), MRP1/2 (ABCC1/2) and BCRP/MXR (ABCG2) proteins. Flow cytometry (FCM) allows determination of the functional expression levels of ABC transporters in live cells, but most dyes used as indicators (rhodamine 123, DiOC2(3), calcein-AM) have limited applicability as they do not detect all three major types of ABC transporters. Dyes with broad coverage (such as doxorubicin, daunorubicin and mitoxantrone) lack sensitivity due to overall dimness and thus may yield a significant percentage of false negative results. We describe two novel fluorescent probes that are substrates for all three common types of ABC transporters and can serve as indicators of MDR in flow cytometry assays using live cells. The probes exhibit fast internalization, favorable uptake/efflux kinetics and high sensitivity of MDR detection, as established by multidrug resistance activity factor (MAF) values and Kolmogorov-Smirnov statistical analysis. Used in combination with general or specific inhibitors of ABC transporters, both dyes readily identify functional efflux and are capable of detecting small levels of efflux as well as defining the type of multidrug resistance. The assay can be applied to the screening of putative modulators of ABC transporters, facilitating rapid, reproducible, specific and relatively simple functional detection of ABC transporter activity, and ready implementation on widely available instruments

Infant and Child Mortality in India in the Last Two Decades: A Geospatial Analysis

Studies examining the intricate interplay between poverty, female literacy, child malnutrition, and child mortality are rare in demographic literature. Given the recent focus on Millennium Development Goals 4 (child survival) and 5 (maternal health), we explored whether the geographic regions that were underprivileged in terms of wealth, female literacy, child nutrition, or safe delivery were also grappling with the elevated risk of child mortality; whether there were any spatial outliers; whether these relationships have undergone any significant change over historical time periods.The present paper attempted to investigate these critical questions using data from household surveys like NFHS 1992-1993, NFHS 1998-1999 and DLHS 2002-2004. For the first time, we employed geo-spatial techniques like Moran's-I, univariate LISA, bivariate LISA, spatial error regression, and spatiotemporal regression to address the research problem. For carrying out the geospatial analysis, we classified India into 76 natural regions based on the agro-climatic scheme proposed by Bhat and Zavier (1999) following the Census of India Study and all estimates were generated for each of the geographic regions.This study brings out the stark intra-state and inter-regional disparities in infant and under-five mortality in India over the past two decades. It further reveals, for the first time, that geographic regions that were underprivileged in child nutrition or wealth or female literacy were also likely to be disadvantaged in terms of infant and child survival irrespective of the state to which they belong. While the role of economic status in explaining child malnutrition and child survival has weakened, the effect of mother's education has actually become stronger over time

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The Economics of Suicide

On April 8th 1994 Kurt Cobain, the lead singer of Nirvana, was found dead in his Seattle home of an apparent shotgun wound to the head and with three times the lethal amount of heroin in his system. A note lay at the scene. The verdict was suicide. Others are sceptical.’ (from www.deathofkurtcobain.com) In the pall of gloom surrounding Michael Jackson’s recent death when we read this extract from a site dedicated to Kurt Cobain, a number of questions struck us as being interesting. Why do famous celebrities commit suicide? Could the reasons be monetary, social or some other phenomenon? Why would such renowned personalities give up an apparent life of luxury? In furthering our understanding of these issues it strikes us as pertinent to ask whether we can ever view suicide from the perspective of an economist. Can we assess human behaviour pertaining to suicide using the ration al science of economics or are we treading on unknown territory in psychiatry instead? Consider a quote by the famous economist Gary Becker from his book The Economic Approach to Human Behaviour

Comparison of MDR activity detection in model cell lines using MDR probes and inhibitors of different specificity.

<p>Average MAF values for three representative experiments are provided, with SD not exceeding 10% for each value.</p

Examples of multiplex (triple) probe treatment for MDR activity profiling in the CHO K1 cell line.

<p>(Average D values for three representative experiments are provided as characteristics of MDR, with SD not exceeding 10% for each value).</p

Detection of the expression levels of three major types of MDR proteins in cultured cell lines using immunostaining with monoclonal antibodies and a flow cytometry assay.

<p>Average D values (± SEM) for three representative experiments are presented.</p

Concentration-dependent inhibitory effect of various general and specific inhibitors on MDR probes accumulation in CHO K1 (panel A), HCT-15 (panel B), HepG2 (panel C) and HL-60/MX1 (panel D) cells.

<p>The following MDR probes were used: eFluxx-ID® Green (filled squares), eFluxx® Gold (filled triangles), calcein AM (grey circles), DiOC₂(3) (open triangles), CMFDA (open diamonds), pheophorbide A (filled diamonds). Cells were stained with the indicated probes in the presence of the various concentrations of the appropriate inhibitors. EC₅₀ values are defined as the concentration of the inhibitor resulting in half-maximum inhibition of dye accumulation.</p