341 research outputs found

    Governors as CEOs: An Evolution

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    This paper examines the emergence of American governors as modern day CEOs from the historical perspective. In the 1960s, the shift in the power of the governorship was beginning, and by the 1970s, the trend toward stronger chief executives was reinforced by various federalism initiatives and the increasing complexity of managing state government. As the 1980s arrived, shifts in federal responsibilities to state governments, economic challenges and competitiveness, increased urbanization, demands for additional services and programs, and accelerating technologies have required a new kind of leadership in the governor’s office. Such leadership requires not only authority, but a managerial expertise and information to be successful and effective as a governor. With this emergence of a “new breed” of governors, the office has acquired a growth in respect and power. Over the last forty years, five out of the last seven U.S presidents were state governors before becoming the country’s chief executive. This is unprecedented in American history. During the first half of the twentieth century, governors mostly functioned in the traditional role as state figurehead in a strongly political framework. They were often not known beyond their state’s boundaries, and they spent an estimated 15% of their time on traditional management and administration. Today, if states were considered corporations, most would be among the Fortune 500 companies! Now governors are functioning more like corporate chief executive officers than traditional politicians. This paper seeks to explain this shift toward governors becoming influential, effective and powerful organizational leaders

    Long-term effects of reduced renal mass in humans

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    Long-term effects of reduced renal mass in humans. The long-term risks of kidney donation have not been well defined. We carried out a meta-analysis of investigations that examined the long-term effects of reduced renal mass in humans. We used multiple linear regression to combine studies and adjust for differences in the duration of follow-up, the reason for reduced renal mass, the type of controls, age and gender. We analyzed 48 studies with 3124 patients and 1703 controls. Unilateral nephrectomy caused a decrement in glomerular filtration rate (-17.1 ml/min; 95% confidence interval -20.2 to -14.0 ml/min) that tended to improve with each 10 years of follow-up (1.4 ml/min/decade; 0.3 to 2.4 ml/min/decade). Patients with single kidneys had small, progressive increases in proteinuria (76 mg/day/decade; 52 to 101 mg/day/decade), but proteinuria was negligible after nephrectomy for trauma or kidney donation. Nephrectomy did not affect the prevalence of hypertension, but there was a small increase in systolic blood pressure (2.4 mm Hg; -0.3 to 5.1 mm Hg, P > 0.05) which rose further with duration of follow-up (1.1 mm Hg/decade; 0.0 to 2.2 mm Hg/decade). Diastolic blood pressure was higher after nephrectomy (3.1 mm Hg; 1.8 to 4.4 mm Hg), but this increment did not change with duration of follow-up. Thus, in normal individuals, unilateral nephrectomy does not cause progressive renal dysfunction, but may be associated with a small increase in blood pressure

    Therapeutic efficacy of favipiravir against Bourbon virus in mice

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    Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV

    Bioactive oat ÎČ-glucan reduces LDL cholesterol in Caucasians and non-Caucasians

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    <p>Abstract</p> <p>Background</p> <p>There is increasing global acceptance that viscous soluble fibers lower serum LDL cholesterol (LDL-C), but most evidence for this comes from studies in Caucasians. To see if oat ÎČ-glucan lowers LDL-C in Caucasians and non-Caucasians we conducted a post-hoc analysis of the results of a randomized, controlled, double-blind, multi-center clinical trial whose primary aim was to determine if molecular-weight (MW) influenced the LDL-C-lowering effect of oat ÎČ-glucan.</p> <p>Results</p> <p>Caucasian and non-Caucasian subjects with LDL-C-C ≄ 3.0 and ≀ 5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 randomized, n = 345 completed, n = 1 excluded for missing ethnicity) were randomly assigned to consume cereal containing wheat-fiber (Control, n = 74:13 Caucasian:non-Caucasian) or 3 g high-MW (3H, 2,250,000 g/mol, n = 67:19), 4 g medium-MW (4 M, 850,000 g/mol, n = 50:17), 3 g medium-MW (3M, 530,000 g/mol, n = 54:9) or 4 g low-MW (4 L, 210,000 g/mol, n = 51:12) oat ÎČ-glucan daily for 4 weeks. LDL-C after 4 weeks was influenced by baseline LDL-C (p < 0.001) and treatment (p = 0.003), but not ethnicity (p = 0.74). In all subjects, compared to control, 3 H, 4 M and 3 M reduced LDL-C significantly by 4.8 to 6.5%, but 4 L had no effect. Compared to control, the bioactive oat ÎČ-glucan treatments (3H, 4M and 3M) reduced LDL-C by a combined mean (95% CI) of 0.18 (0.06, 0.31) mmol/L (4.8%, n = 171, p = 0.004) in Caucasians, a value not significantly different from the 0.37 (0.09, 0.65) mmol/L (10.3%, n = 45, p = 0.008) reduction in non-Caucasians.</p> <p>Conclusion</p> <p>We conclude that oat ÎČ-glucan reduces LDL-C in both Caucasians and non-Caucasians; there was insufficient power to determine if the magnitude of LDL-C-lowering differed by ethnicity.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981981">NCT00981981</a></p

    A randomised trial of an internet weight control resource: The UK Weight Control Trial [ISRCTN58621669]

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    BACKGROUND: Obesity treatment is notoriously unsuccessful and one of the barriers to successful weight loss reported by patients is a lack of social support. The Internet offers a novel and fast approach to the delivery of health information, enabling 24-hour access to help and advice. However, much of the health information available on the Internet is unregulated or not written by qualified health professionals to provide unbiased information. The proposed study aims to compare a web-based weight loss package with traditional dietary treatment of obesity in participants. The project aims to deliver high quality information to the patient and to evaluate the effectiveness of this information, both in terms of weight loss outcomes and cost-effectiveness. METHODS: This study is a randomised controlled trial of a weight loss package against usual care provided within General Practice (GP) surgeries in Leeds, UK. Participants will be recruited via posters placed in participating practices. A target recruitment figure of 220 will enable 180 people to be recruited (allowing for 22% dropout). Participants agreeing to take part in the study will be randomly allocated using minimisation to either the intervention group, receiving access to the Internet site, or the usual care group. The primary outcome of the study will be the ability of the package to promote change in BMI over 6 and 12 months compared with traditional treatment. Secondary outcomes will be the ability of the Internet package to promote change in reported lifestyle behaviours. Data will be collected on participant preferences, adherence to treatment, health care use and time off work. Difference in cost between groups in provision of the intervention and the cost of the primary outcome will also be estimated. CONCLUSION: A positive result from this study would enhance the repertoire of treatment approaches available for the management of obesity. A negative result would be used to inform the research agenda and contribute to redefining future strategies for tackling obesity

    A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

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    It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s−1^{-1} and an ejecta mass of few ×10−5\times 10^{-5} M⊙_{\odot}. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

    Differential effects of speech and Language therapy and rTMS in chronic versus subacute post-stroke aphasia: Results of the NORTHSTAR-CA trial

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    Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (\u3e6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment. Chronic and subacute results were compared. Results: Adverse events were rare, mild, and did not differ between groups. Language outcomes improved significantly in all groups irrespective of treatment and recovery phase. At 30-day follow-up, there was a significant interaction of stimulation and recovery phase on naming recovery (P \u3c.001). Naming recovery with rTMS was larger in subacute (Mdn = 1.91/IQR =.77) than chronic patients (Mdn =.15/IQR = 1.68/P =.015). There was no significant rTMS effect in the chronic aphasia group. Conclusions: The addition of rTMS to SLT led to significant supplemental gains in naming recovery in the subacute phase only. While this needs confirmation in larger studies, our results clarify neuromodulatory vs training-induced effects and indicate a possible window of opportunity for contralesional inhibitory stimulation interventions in post-stroke aphasia. NORTHSTAR trial registration: https://clinicaltrials.gov/ct2/show/NCT02020421

    Mercury isotope evidence for Arctic summertime re-emission of mercury from the cryosphere

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    During Arctic springtime, halogen radicals oxidize atmospheric elemental mercury (Hg-0), which deposits to the cryosphere. This is followed by a summertime atmospheric Hg-0 peak that is thought to result mostly from terrestrial Hg inputs to the Arctic Ocean, followed by photoreduction and emission to air. The large terrestrial Hg contribution to the Arctic Ocean and global atmosphere has raised concern over the potential release of permafrost Hg, via rivers and coastal erosion, with Arctic warming. Here we investigate Hg isotope variability of Arctic atmospheric, marine, and terrestrial Hg. We observe highly characteristic Hg isotope signatures during the summertime peak that reflect re-emission of Hg deposited to the cryosphere during spring. Air mass back trajectories support a cryospheric Hg emission source but no major terrestrial source. This implies that terrestrial Hg inputs to the Arctic Ocean remain in the marine ecosystem, without substantial loss to the global atmosphere, but with possible effects on food webs.Arctic warming thaws permafrost, leading to enhanced soil mercury transport to the Arctic Ocean. Mercury isotope signatures in arctic rivers, ocean and atmosphere suggest that permafrost mercury is buried in marine sediment and not emitted to the global atmospherePeer reviewe

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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