Inequality and Production Elasticity

We address a contention regarding capital deepening when the labor share of income declines and the elasticity of substitution is above unity between Karabarbounis and Neiman (2013) and Elsby et. al (2013). We demonstrate the incentive for technical change, which increases inequality and how investments in new technology create temporal misalignment between a decrease in the labor share of income and capital deepening. We show how the decline in the saving rate that occurred during the 80's and 90's may resolve the contention regarding capital deepening. We find that elasticity of substitution below unity is less consistent with the decline in the labor share of income. A second contention is whether the elasticity of substitution is above or below unity. We perform a time-varying state-space estimation of the evolution of elasticity using the unadjusted marginal product of labor and the Kalman Filter. We find that the elasticity between capital and labor has been fluctuating slightly above unity since 1980, which is consistent with our theoretical findings. We note that an elasticity of substitution above unity has important implications for balanced growth under capital augmentation

TEs or not TEs? That is the evolutionary question

Transposable elements (TEs) have contributed a wide range of functional sequences to their host genomes. A recent paper in BMC Molecular Biology discusses the creation of new transcripts by transposable element insertion upstream of retrocopies and the involvement of such insertions in tissue-specific post-transcriptional regulation

Inequality, Technical Change or Leverage?

Exploring the determinants of growing income inequality, I show how constant capital income shares and inequality can be explained without technical change. I show why despite the fact that technical change is capital augmenting, rather than labor augmenting, it may not be sufficient to explain the last few decades of growing capital share of income and inequality due to the balancing mechanism of depreciation. Finally, I show how the growth of leverage, which coincided with the growth of inequality, can explain the growth of capital share of income and inequality. I introduce a simple model of leverage and business cycle and show how leverage is justified by more leverage and how depressed interest rate allows leveraging and inequality growth to persist

Inequality and Production Elasticity

We address a contention regarding capital deepening when the labor share of income declines and the elasticity of substitution is above unity between Karabarbounis and Neiman (2013) and Elsby et. al (2013). We demonstrate the incentive for technical change, which increases inequality and how investments in new technology create temporal misalignment between a decrease in the labor share of income and capital deepening. We show how the decline in the saving rate that occurred during the 80's and 90's may resolve the contention regarding capital deepening. We find that elasticity of substitution below unity is less consistent with the decline in the labor share of income. A second contention is whether the elasticity of substitution is above or below unity. We perform a time-varying state-space estimation of the evolution of elasticity using the unadjusted marginal product of labor and the Kalman Filter. We find that the elasticity between capital and labor has been fluctuating slightly above unity since 1980, which is consistent with our theoretical findings. We note that an elasticity of substitution above unity has important implications for balanced growth under capital augmentation

Comparison of body mass index and body surface area as outcome predictors in patients with systolic heart failure

Background: We investigated whether the ‘obesity paradox’ in heart failure (HF) is influenced by common confounders, and assessed if body surface area (BSA) may correlate more closely than body mass index (BMI) with prognosis. Methods: We studied 630 systolic HF patients at their initial visit to the HF clinic. Body size was measured by BMI and BSA. The association between body indices and mortality was assessed by Cox proportional-hazard analyses. Results: There were 248 deaths during mean follow-up of 39 months. A progressive inverse association of BMI and BSA tertiles (T1–T3) with mortality risk was observed (for BSA: T3, reference, T2, hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.01–1.95, p = 0.04 and T1, HR = 1.78, 95% CI 1.29–2.45, p < 0.001; for BMI: T3, reference, T2, HR = 1.29, 95% CI 0.92–1.79, p = 0.13 and T1, HR = 1.66, 95% CI 1.21–2.27, p = 0.002). The obesity paradox was attenuated after multivariate adjustment, and did not persist after adjustment for age alone (for BMI: T3, reference, T2, HR = 1.13, 95% CI 0.81–1.58, p = 0.47; T1, HR = 1.30, 95% CI 0.94–1.80, p = 0.12; for BSA: T3, reference, T2, HR = 0.96, 95% CI 0.68–1.35, p = 0.82; T1, HR = 1.15, 95% CI 0.82–1.63, p = 0.42). Conclusions: BSA provides prognostic information similar to BMI in systolic HF. However, the obesity paradox of both BMI and BSA in HF may be confounded by the younger age of the obese patients.

The Alternative Choice of Constitutive Exons throughout Evolution

Alternative cassette exons are known to originate from two processes exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exons suggests that the common ancestors were constitutively spliced. We show that relaxation of the 59 splice site during evolution is one of the molecular mechanisms by which exons shift from constitutive to alternative splicing. This shift is associated with the fixation of exonic splicing regulatory sequences (ESRs) that are essential for exon definition and control the inclusion level only after the transition to alternative splicing. The effect of each ESR on splicing and the combinatorial effects between two ESRs are conserved from fish to human. Our results uncover an evolutionary pathway that increases transcriptome diversity by shifting exons from constitutive to alternative splicin

Economic case for stratified medicine

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2007.Includes bibliographical references (leaves 36-39).The goal of this study is to explore the economic conditions that favor the joint development of therapeutics and companion diagnostics. I hypothesize that predictive biomarkers can generate economic value in drug development by increasing success rates. I construct an economic model of the development of a hypothetical new therapy, and devote particular attention to parameters regarding safety, efficacy, cost, and market size, within a decision-theoretic framework. The results include a characterization of the dynamic net present value trade-offs between stratum size and biomarker success, as well as the identification of two complementary concepts of stratified medicine, namely, disease reclassification and value-based reimbursement. I also identify a strong potential incentive mechanism in the hands of public policy makers that could facilitate a resolution of the tension between patient interests and the interests of pharmaceutical sponsors. The conclusion is that a biomarker can compensate for smaller stratum by increasing success probabilities. However, the effects of longer development time due to biomarker inclusion counter the effects of improved success probabilities. Longer exclusivity periods for stratified medicine may be required in order to resolve the tension between patient interests and the interests of pharmaceutical sponsors.by Amir Goren.S.M

Overlapping Splicing Regulatory Motifs—Combinatorial Effects on Splicing

Regulation of splicing in eukaryotes occurs through the coordinated action of multiple splicing factors. Exons and introns contain numerous putative binding sites for splicing regulatory proteins. Regulation of splicing is presumably achieved by the combinatorial output of the binding of splicing factors to the corresponding binding sites. Although putative regulatory sites often overlap, no extensive study has examined whether overlapping regulatory sequences provide yet another dimension to splicing regulation. Here we analyzed experimentally-identified splicing regulatory sequences using a computational method based on the natural distribution of nucleotides and splicing regulatory sequences. We uncovered positive and negative interplay between overlapping regulatory sequences. Examination of these overlapping motifs revealed a unique spatial distribution, especially near splice donor sites of exons with weak splice donor sites. The positively selected overlapping splicing regulatory motifs were highly conserved among different species, implying functionality. Overall, these results suggest that overlap of two splicing regulatory binding sites is an evolutionary conserved widespread mechanism of splicing regulation. Finally, over-abundant motif overlaps were experimentally tested in a reporting minigene revealing that overlaps may facilitate a mode of splicing that did not occur in the presence of only one of the two regulatory sequences that comprise it