Proportionate vs disproportionate distribution of wealth of two individuals in a tempered Paretian ensemble

We study the distribution P(\omega) of the random variable \omega = x_1/(x_1 + x_2), where x_1 and x_2 are the wealths of two individuals selected at random from the same tempered Paretian ensemble characterized by the distribution \Psi(x) \sim \phi(x)/x^{1 + \alpha}, where \alpha > 0 is the Pareto index and $\phi(x)$ is the cut-off function. We consider two forms of \phi(x): a bounded function \phi(x) = 1 for L \leq x \leq H, and zero otherwise, and a smooth exponential function \phi(x) = \exp(-L/x - x/H). In both cases \Psi(x) has moments of arbitrary order. We show that, for \alpha > 1, P(\omega) always has a unimodal form and is peaked at \omega = 1/2, so that most probably x_1 \approx x_2. For 0 < \alpha < 1 we observe a more complicated behavior which depends on the value of \delta = L/H. In particular, for \delta < \delta_c - a certain threshold value - P(\omega) has a three-modal (for a bounded \phi(x)) and a bimodal M-shape (for an exponential \phi(x)) form which signifies that in such ensembles the wealths x_1 and x_2 are disproportionately different.Comment: 9 pages, 8 figures, to appear in Physica

Effectiveness of technology-assisted case management in low income adults with type 2 diabetes (TACM-DM): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>An estimated 1 in 3 American adults will have diabetes by the year 2050. Nationally, South Carolina ranks 10^thin cases of diagnosed diabetes compared to other states. In adults, type 2 diabetes (T2DM) accounts for approximately 90-95% of all diagnosed cases of diabetes. Clinically, provider and health system factors account for < 10% of the variance in major diabetes outcomes including hemoglobin A1c (HbA1c), lipid control, and resource use. Use of telemonitoring systems offer new opportunities to support patients with T2DM while waiting to be seen by their health care providers at actual office visits. A variety of interventions testing the efficacy of telemedicine interventions have been conducted, but the outcomes have yielded equivocal results, emphasizing the shortage of controlled, randomized trials in this area. This study provides a unique opportunity to address this gap in the literature by optimizing two strategies that have been shown to improve glycemic control, while simultaneously implementing clinical outcomes measures, using a sufficient sample size, and offering health care delivery to rural, underserved and low income communities with T2DM who are seen at Federally Qualified Health Centers (FQHCs) in coastal South Carolina.</p> <p>Methods</p> <p>We describe a four-year prospective, randomized clinical trial, which will test the effectiveness of technology-assisted case management in low income rural adults with T2DM. Two-hundred (200) male and female participants, 18 years of age or older and with an HbA1c ≥ 8%, will be randomized into one of two groups: (1) an intervention arm employing the innovative FORA system coupled with nurse case management or (2) a usual care group. Participants will be followed for 6-months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that among indigent, rural adult patients with T2DM treated in FQHC's, participants randomized to the technology-assisted case management intervention will have significantly greater reduction in HbA1c at 6 months of follow-up compared to usual care.</p> <p>Discussion</p> <p>Results from this study will provide important insight into the effectiveness of technology-assisted case management intervention (TACM) for optimizing diabetes care in indigent, rural adult patients with T2DM treated in FQHC's.</p> <p>Trial Registration</p> <p>National Institutes of Health Clinical Trials Registry (<url>http://ClinicalTrials.gov</url> identifier# <a href="http://www.clinicaltrials.gov/ct2/show/NCT01373489">NCT01373489</a></p

Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis

Purpose: Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis. Methods: Evolutionarily conserved differentially expressed genes were identified through in silico analysis, with in situ hybridization, gene knockdown, and rescue performed to confirm spatiotemporal gene expression and phenotype. Interrogation of the 100,000 Genomes Project for putative pathogenic variants was performed. Results: Nine conserved differentially expressed genes between zebrafish and mouse were identified. Expression of zebrafish ank3a, bmpr1ba/b, cdh4, and pdgfaa was localized to the OF, periocular mesenchyme cells, or ciliary marginal zone, regions traversed by the OF. Knockdown of ank3, bmpr1b, and pdgfaa revealed a coloboma and/or microphthalmia phenotype. Novel pathogenic variants in ANK3, BMPR1B, PDGFRA, and CDH4 were identified in 8 unrelated coloboma families. We showed BMPR1B rescued the knockdown phenotype but variant messenger RNAs failed, providing evidence of pathogenicity. Conclusion: We show the utility of cross-species meta-analysis to identify several novel coloboma disease-causing genes. There is a potential to increase the diagnostic yield for new and unsolved patients while adding to our understanding of the genetic basis of OF morphogenesis

Assessing the digenic model in rare disorders using population sequencing data

An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples

A systematic review on the effectiveness of physical and rehabilitation interventions for chronic non-specific low back pain

Low back pain (LBP) is a common and disabling disorder in western society. The management of LBP comprises a range of different intervention strategies including surgery, drug therapy, and non-medical interventions. The objective of the present study is to determine the effectiveness of physical and rehabilitation interventions (i.e. exercise therapy, back school, transcutaneous electrical nerve stimulation (TENS), low level laser therapy, education, massage, behavioural treatment, traction, multidisciplinary treatment, lumbar supports, and heat/cold therapy) for chronic LBP. The primary search was conducted in MEDLINE, EMBASE, CINAHL, CENTRAL, and PEDro up to 22 December 2008. Existing Cochrane reviews for the individual interventions were screened for studies fulfilling the inclusion criteria. The search strategy outlined by the Cochrane Back Review Groups (CBRG) was followed. The following were included for selection criteria: (1) randomized controlled trials, (2) adult (≥18 years) population with chronic (≥12 weeks) non-specific LBP, and (3) evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work). Two reviewers independently selected studies and extracted data on study characteristics, risk of bias, and outcomes at short, intermediate, and long-term follow-up. The GRADE approach was used to determine the quality of evidence. In total 83 randomized controlled trials met the inclusion criteria: exercise therapy (n = 37), back school (n = 5), TENS (n = 6), low level laser therapy (n = 3), behavioural treatment (n = 21), patient education (n = 1), traction (n = 1), and multidisciplinary treatment (n = 6). Compared to usual care, exercise therapy improved post-treatment pain intensity and disability, and long-term function. Behavioural treatment was found to be effective in reducing pain intensity at short-term follow-up compared to no treatment/waiting list controls. Finally, multidisciplinary treatment was found to reduce pain intensity and disability at short-term follow-up compared to no treatment/waiting list controls. Overall, the level of evidence was low. Evidence from randomized controlled trials demonstrates that there is low quality evidence for the effectiveness of exercise therapy compared to usual care, there is low evidence for the effectiveness of behavioural therapy compared to no treatment and there is moderate evidence for the effectiveness of a multidisciplinary treatment compared to no treatment and other active treatments at reducing pain at short-term in the treatment of chronic low back pain. Based on the heterogeneity of the populations, interventions, and comparison groups, we conclude that there are insufficient data to draw firm conclusion on the clinical effect of back schools, low-level laser therapy, patient education, massage, traction, superficial heat/cold, and lumbar supports for chronic LBP

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered