413 research outputs found

    Electoral Certainty and Policy Uncertainty in Authoritarian Regimes: Russia as a Case Study

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    Under the guidance of Professor Rivera, I attempted to study two hypotheses using the data on perceptions of Russian elites. The two hypotheses respectively question the influence of (1) Russian elites on electoral uncertainty and (2) Russian elites on policy uncertainty. First, I explored the established relationship between authoritarianism and uncertainty, especially from a comparative perspective with case-studies from authoritarian countries around the world. Second, I investigated the case of both electoral and policy (un)certainty in Russia to explain why it is reasonable to use Russia as an empirical case to test the hypotheses. Followed by the literature review section, I will present the data analysis on uncertainty in electoral and policy outcomes, especially by looking at predictive perceptions rather than past results (i.e., perceptions of political succession and stability in the future). The conclusion will demonstrate whether the data confirms my hypotheses and how my study contributes to the current literature resources on this topic

    Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.

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    To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence. The induction of P53 appeared to affect dendritic branching in Rett neurons, as P53 inhibition restored dendritic complexity. The induction of P53 targets was also detectable in analyses of human Rett patient brain, suggesting that this disease-in-a-dish model can provide relevant insights into the human disorder

    Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC^4RS) and ground-based (SOAS) observations in the Southeast US

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    Formation of organic nitrates (RONO_2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NO_x), but the chemistry of RONO_2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO_2) in the GEOS-Chem global chemical transport model with  ∼  25  ×  25 km^2 resolution over North America. We evaluate the model using aircraft (SEAC^4RS) and ground-based (SOAS) observations of NO_x, BVOCs, and RONO_2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO_2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25–50 % of observed RONO_2 in surface air, and we find that another 10 % is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10 % of observed boundary layer RONO_2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO_3 accounts for 60 % of simulated gas-phase RONO_2 loss in the boundary layer. Other losses are 20 % by photolysis to recycle NO_x and 15 % by dry deposition. RONO_2 production accounts for 20 % of the net regional NO_x sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NO_x emissions. This segregation implies that RONO_2 production will remain a minor sink for NO_x in the Southeast US in the future even as NO_x emissions continue to decline

    Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals

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    Background: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. Methods: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages ( > 0 years). Findings: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91–0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37–1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9–2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58–1·64), and did so earlier in life than those from the most affluent group (adjusted difference −3·51 years, 95% CI −3·77 to −3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. Interpretation: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. Funding: British Heart Foundation and National Institute for Health Research

    Clinical Implications of Combinatorial Pharmacogenomic Tests Based on Cytochrome P450 Variant Selection

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    Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of a given population with an “altered metabolizer” genotype predicted phenotype, where a CPGx test targeted both gene variants a prospective diplotypes. A potential genotype predicted phenotype was considered an altered metabolizer when it resulted in medication therapy modification based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Targeted variant CPGx tests found in the Genetic Testing Registry (GTR), gene selection information, and diplotype frequency data from the Pharmacogenomics Knowledge Base (PharmGKB) were used to determine the detection rate of each CPGx test. Our results indicated that the detection rate of CPGx tests covering CYP2C19, CYP2C9, CYP2D6, and CYP2B6 show significant variation across ethnic groups. Specifically, the Sub-Saharan Africans have 63.9% and 77.9% average detection rates for CYP2B6 and CYP2C19 assays analyzed, respectively. In addition, East Asians (EAs) have an average detection rate of 55.1% for CYP2C9 assays. Therefore, the patient’s ethnic background should be carefully considered in selecting CPGx tests

    Perceptions of a mobile health intervention for Community Case Management in Malawi: Opportunities and challenges for Health Surveillance Assistants in a community setting

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    AbstractBackground Improved availability of mobile phones in low- and middle-income countries (LMICs) offer an opportunity to improve delivery of Community Case Management (CCM). Despite enthusiasm for introducing mHealth into healthcare across LMICs, end-user attitudes towards mHealth solutions for CCM are limited. We aimed to explore Health Surveillance Assistants’ (HSAs) perceptions of the Supporting LIFE electronic CCM Application (SL eCCM App) and their experiences incorporating it as part of their clinical practice. Methods This exploratory qualitative study was part of a mixed methods feasibility study investigating whether children under-5 presenting to village clinics could be followed-up to collect patient outcome data. The convenience sample of 12 HSAs enrolled into the feasibility study participated in semi-structured interviews, which were conducted at village clinics after HSAs had field-tested the SL eCCM App over a 10-day period. Interviews explored HSAs perceptions of the SL eCCM App and their experiences in using the App in addition to paper CCM to assess and treat acutely unwell children. Open coding was used to label emerging concepts, which were iteratively defined and developed into six key themes. Results HSAs’ perceived enhanced clinical decision-making, quality of CCM delivery, and work efficiency as opportunities associated with using the SL eCCM App. HSAs believed the inability to retrieve patient records,, cumbersome duplicate assessments/data entry study procedures, and inconsistencies between the SL eCCM App and paper-based CCM guidelines as challenges to implementation. Adding features to the App, such as, permitting communication between colleagues/supervisors, drug stock-out reporting, and community assessments, were identified as potentially supporting HSAs’ many roles in the community. Conclusion This study identified opportunities and challenges associated with using the SL eCCM App in Malawi. This information can be used to inform future development and evaluation of the SL eCCM App, and similar mHealth solutions for CCM in Malawi and other developing countries.

    Low-Mass Seyfert 2 Galaxies in the Sloan Digital Sky Survey

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    (Abridged) We describe a sample of low-mass Seyfert 2 galaxies selected from the Sloan Digital Sky Survey, having a median absolute magnitude of M_g = -19.0 mag. These galaxies are Type 2 counterparts to the Seyfert 1 galaxies with intermediate-mass black holes identified by Greene & Ho (2004). Spectra obtained with the Echellette Spectrograph and Imager at the Keck Observatory are used to determine the central stellar velocity dispersions and to examine the emission-line properties. Overall, the stellar velocity dispersions are low (40-90 km/s), and we find 12 objects having sigma < 60 km/s, a range where very few Seyfert 2 galaxies were previously known. The sample follows the correlation between stellar velocity dispersion and FWHM([OIII]) seen in more massive Seyfert galaxies, indicating that the narrow-line FWHM values are largely determined by virial motion of gas in the central regions of the host galaxies. Using estimates of the black hole masses and AGN bolometric luminosities, we find that these galaxies are typically radiating at a high fraction of their Eddington rate, with a median L_bol/L_Edd = 0.4. We identify one galaxy, SDSS J110912.40+612346.7, as a Type 2 analog of the nearby dwarf Seyfert 1 galaxy NGC 4395, with a nearly identical narrow-line spectrum and a dwarf spiral host of only M_g = -16.8 mag. Forthcoming observations of this sample, including X-ray and mid-infrared spectroscopy, can provide new tests of the obscuring torus model for active galaxies at low luminosities.Comment: 34 pages, 16 figures. Some figures bitmapped to reduce size. To appear in A

    Host Galaxies of Luminous Type 2 Quasars at z ~ 0.5

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    We present deep Gemini GMOS optical spectroscopy of nine luminous quasars at redshifts z ~ 0.5, drawn from the SDSS type 2 quasar sample. Our targets were selected to have high intrinsic luminosities (M_V < -26 mag) as indicated by the [O III] 5007 A emission-line luminosity (L_[O III]). Our sample has a median black hole mass of ~ 10^8.8 M_sun inferred assuming the local M_BH-sigma_* relation and a median Eddington ratio of ~ 0.7, using stellar velocity dispersions sigma_* measured from the G band. We estimate the contamination of the stellar continuum from scattered quasar light based on the strength of broad H-beta, and provide an empirical calibration of the contamination as a function of L_[O III]; the scattered light fraction is ~ 30% of L_5100 for objects with L_[O III] = 10^9.5 L_sun. Population synthesis indicates that young post-starburst populations (< 0.1 Gyr) are prevalent in luminous type 2 quasars, in addition to a relatively old population (> 1 Gyr) which dominates the stellar mass. Broad emission complexes around He II 4686 A with luminosities up to 10^8.3 L_sun are unambiguously detected in three out of the nine targets, indicative of Wolf-Rayet populations. Population synthesis shows that ~ 5-Myr post-starburst populations contribute substantially to the luminosities (> 50% of L_5100) of all three objects with Wolf-Rayet detections. We find two objects with double cores and four with close companions. Our results may suggest that luminous type 2 quasars trace an early stage of galaxy interaction, perhaps responsible for both the quasar and the starburst activity.Comment: 20 pages, 13 figures, 7 tables; accepted to Ap
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