Conflicts in Development: Tourism and the Cattle Industry in Brazil

This paper challenges the conventional view that where there is a political elite, economic development will proceed along lines that sacrifice future generations for the benefit of the current ruling class. We find that shortfalls in the balance of payments will cause those in authority to promote activities that encourage tourism as a solution to balance of payments deficit. The vehicle for generating tourism is the provision of public goods. More traditional paths toward development particularly cattle ranching are displaced by tourist attractions. While motivated by myopic self-interest, the pursuit of public goods reduces the amount of debt transferred to future generations and thereby serves to redistribute wealth inter-temporally. Brazil over the period 1965 until 1998 is used as a test case

SCH 48973: a Potent, Broad-Spectrum, Antienterovirus Compound.

SCH 48973 is a novel molecule with potent, selective, antienterovirus activity. In assays of the cytopathic effect against five picornaviruses, SCH 48973 had antiviral activity (50% inhibitory concentrations [IC50s]) of 0.02 to 0.11 microg/ml, with no detectable cytotoxicity at 50 microg/ml. SCH 48973 inhibited 80% of 154 recent human enterovirus isolates at an IC50 of 0.9 microg/ml. The antiviral activity of SCH 48973 is derived from its specific interaction with viral capsid, as confirmed by competition binding studies. The affinity constant (Ki) for SCH 48973 binding to poliovirus was 8.85 x 10(-8) M. In kinetic studies, a maximum of approximately 44 molecules of SCH 48973 were bound to poliovirus capsid. SCH 48973 demonstrated efficacy in a murine poliovirus model of enterovirus disease. SCH 48973 increased the survival of infected mice when it was administered orally at dosages of 3 to 20 mg/kg of body weight/day. Oral administration of SCH 48973 also reduced viral titers in the brains of infected mice. On the basis of its in vitro and in vivo profiles, SCH 48973 represents a potential candidate for therapeutic intervention against enterovirus infections

Selective elimination of pluripotent stem cells by PIKfyve specific inhibitors.

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their ability to form teratocarcinomas in mice, and intraperitoneal injections of WX8 into mice harboring teratocarcinoma xenografts selectively eliminated pluripotent cells. Differentiated cells continued to proliferate, but at a reduced rate. These results provide a proof of principle that PIKfyve specific inhibitors can selectively eliminate pluripotent stem cells in vivo as well as in vitro

Outbreak of Mycobacterium chelonae Infection Associated with Tattoo Ink

Background In January 2012, on the basis of an initial report from a dermatologist, we began to investigate an outbreak of tattoo-associated Mycobacterium chelonae skin and softtissue infections in Rochester, New York. The main goals were to identify the extent, cause, and form of transmission of the outbreak and to prevent further cases of infection. Methods We analyzed data from structured interviews with the patients, histopathological testing of skin-biopsy specimens, acid-fast bacilli smears, and microbial cultures and antimicrobial susceptibility testing. We also performed DNA sequencing, pulsed-field gel electrophoresis (PFGE), cultures of the ink and ingredients used in the preparation and packaging of the ink, assessment of source water and faucets at tattoo parlors, and investigation of the ink manufacturer. Results Between October and December 2011, a persistent, raised, erythematous rash in the tattoo area developed in 19 persons (13 men and 6 women) within 3 weeks after they received a tattoo from a single artist who used premixed gray ink; the highest occurrence of tattooing and rash onset was in November (accounting for 15 and 12 patients, respectively). The average age of the patients was 35 years (range, 18 to 48). Skin-biopsy specimens, obtained from 17 patients, showed abnormalities in all 17, with M. chelonae isolated from 14 and confirmed by means of DNA sequencing. PFGE analysis showed indistinguishable patterns in 11 clinical isolates and one of three unopened bottles of premixed ink. Eighteen of the 19 patients were treated with appropriate antibiotics, and their condition improved. Conclusions The premixed ink was the common source of infection in this outbreak. These findings led to a recall by the manufacturer

A Framework For Detecting Noncoding Rare-Variant associations of Large-Scale Whole-Genome Sequencing Studies

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 toPMed samples. We also analyze five non-lipid toPMed traits

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences

Organizational Behavior in Private Nonprofits: A Study of Liberal Arts Colleges

An effort is made to examine empirically the behavior of private nonprofit liberal arts colleges. The conventional wisdom that nonprofits arise to insure quality in a context of asymmetric information, and that behavior is driven by the need to insure implicit contract compliance is studied. A three-equation model is estimated for the demand price and quality of liberal arts education. Among the conclusions are that consumers are able to acquire and respond to information, that market forces analogous to those in the private sector insure contract compliance and that price premia are not systematically related to quality differentials. The endowment proves to be a means of moderating price increases rather than an end in itself

Managerial Efficiency in Nonprofit Private Higher Education

Traditional market indicators (profits, stock prices, etc.) are absent in the nonprofit sector, and, given the shortcomings of variance analysis in analyzing nonprofit budgets, the potential for conflicts between the principal (providers of funds) and the agent (management) abound. Resource-providers to nonprofit entities need a framework in which to evaluate management performance in terms of the efficient use of resources. Based on data obtained from a sample of 33 Tennessee county jails, Hayes and Millar (1990) used a translog budget model to test the responsiveness of cost shares to changes in relative input prices and operating characteristics. Their study presented empirical results that implied managerial responsiveness to such changes. Out study extends that of Hayes and Millar by using a translog budget model to investigate management response to changes in relative input prices and operating characteristics in a nonprofit higher education setting. A system of translog cost and cost share equations is used to analyze data obtained from a national sample of 349 liberal arts colleges. Results of this study are generally consistent with those in the Hayes-Millar study. The translog model is an appropriate approximation of the cost function, and cost shares vary significantly with variations in input prices and operating characteristics of private nonprofit colleges. The results imply that managers do vary their input mix in response to changes in relative input prices and to changes in the operating characteristics. College managements appear to be concerned with efficiency both allocatively and technically