The role of entrepreneurship, innovation, and urbanity-diversity on growth, unemployment, and income: US state-level evidence and an fsQCA elucidation

The purpose of this study is to consider the differing roles played by combinations of dimensions of entrepreneurship, innovation and geography (here - urbanity-diversity) on United States (US) state level growth, unemployment and income. Fuzzy-set Qualitative Comparative Analysis (fsQCA) forms the primary methodology to investigate these potential roles. One important developmental feature of the analysis is the use of a novel fuzzy membership score creation process, undertaken to calibrate the considered condition and outcome variables. Moreover, fuzzy cluster analyses are undertaken, using the fuzzy c-means technique, on sets of constituent variables to produce sets of clusters interpretable to the relevant condition and outcome variables. A series of fsQCA investigations are undertaken across the different outcome variables of growth, unemployment and income. The main results of the study are that high growth entrepreneurship and innovation are key to economic growth but may require additional (though differing) supporting entrepreneurial activities and processes depending on the economic geography of the State. With regards to unemployment, it is Main Street Entrepreneurship that was consistently present for absence of unemployment causal-recipes and its absence in four of the five high unemployment causal-recipes, the absence of Urbanity-diversity was consistently shown in absence of unemployment causal-recipes and its present in three of the five high unemployment complex causal-recipes. For income, the presence of Innovation in all the high income causal-recipes and its absence in three of the four absence of income causal-recipes, Urbanity-diversity present in two of the three high income causal-recipes, and absent in three of the four absence of income causal-recipes. Overall, the results of the study suggest that for non urban-diverse states, the presence of Innovation, Growth Entrepreneurship and Main Street, and relative absence of start-up activity is of relevance in supporting positive growth, unemployment and income outcomes. For more urban-diverse states however, this combination of factors is less effective in generating positive outcomes across all three variables, suggesting trade-offs needing to be considered in these more complex economies. This study contributes to the theory of entrepreneurship and innovation by offering new insights into how different combinations of entrepreneurship, innovation and the urbanity-diversity affect growth, unemployment and income levels across different US states, consequently informing entreprenurship policy practice in terms of which policies work most effectively in which conditions. The novel applied and technical developments demonstrated in the study offer novel implementations on this area of research

An in vivo control map for the eukaryotic mRNA translation machinery

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis

Assaying activity and assessing thermostability of hyperthermophilic enzymes

There is now a wide variety of intra- and extra-cellular enzymes available from organisms growing above 75°C, and having sufficient stability to allow assay well above this temperature. For some of these enzymes, to assay below even 95°C will involve measurement below the optimal growth temperature for the organism. The purpose of this chapter is to cover practical aspects of enzyme assay procedures that are specific to high temperatures. Since by far the commonest routine assessment of enzyme stability is activity loss, and because it is always unwise to measure enzyme activity without being confident of its stability during the assay, we include an outline of procedures for measuring enzyme activity loss/stability at high temperatures

Selection Criteria for the Radical Treatment of Locally Advanced Rectal Cancer

There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T3/T4) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22–42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas

The utility of diagnostic selective nerve root blocks in the management of patients with lumbar radiculopathy: a systematic review.

OBJECTIVE: Lumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery. DESIGN: Systematic review of diagnostic test accuracy studies. ELIGIBILITY CRITERIA: Primary research articles using a patient population with low back pain and symptoms in the leg, SNRB administered under radiological guidance as index test, and any reported reference standard for the diagnosis of LR. INFORMATION SOURCES: MEDLINE (Ovid), MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index, Biosis, LILACS, Dissertation abstracts and National Technical Information Service from inception to 2018. METHODS: Risk of bias and applicability was assessed using the QUADAS-2 tool. We performed random-effects logistic regression to meta-analyse studies grouped by reference standard. RESULTS: 6 studies (341 patients) were included in this review. All studies were judged at high risk of bias. There was substantial heterogeneity across studies in sensitivity (range 57%-100%) and specificity (10%-86%) estimates. Four studies were diagnostic cohort studies that used either intraoperative findings during surgery (pooled sensitivity: 93.5% [95% CI 84.0 to 97.6]; specificity: 50.0% [16.8 to 83.2]) or 'outcome following surgery' as the reference standard (pooled sensitivity: 90.9% [83.1 to 95.3]; specificity 22.0% [7.4 to 49.9]). Two studies had a within-patient case-control study design, but results were not pooled because different types of control injections were used. CONCLUSIONS: We found limited evidence which was of low methodological quality indicating that the diagnostic accuracy of SNRB is uncertain and that specificity in particular may be low. SNRB is a safe test with a low risk of clinically significant complications, but it remains unclear whether the additional diagnostic information it provides justifies the cost of the test.National Institute for Health Research Health Technology Assessment programme grant (project number 09/111/01)

Differing commissioning arrangements may contribute to geographic variation in clinical management of digital ulcers in systemic sclerosis

Phosphodiesterase inhibitors (such as sildenafil) and endothelin receptor antagonist, bosentan, are effective for digital ulcer disease in systemic sclerosis (SSc-DU) and are endorsed in international treatment recommendations. Commissioning of high-cost drugs, such as bosentan, however, differs across devolved nations of the UK. We report a multicentre service evaluation project to examine ‘real world’ management of SSc-DU before and following the 2015 UK Scleroderma Study Group (UKSSG) guidance, across southwest (SW) England and Wales. Results showed that iloprost and sildenafil use for SSc-DU was higher in patients in Wales prior to 2015. Between 2015–2017, sildenafil use for SSc-DU increased in SW England while remaining stable in Wales. Bosentan use for SSc-DU after 2015 in SW England increased, while remaining stable and proportionately lower in Wales. These findings demonstrate that differing commissioning guidance across devolved nations of the UK seems to contribute to geographic variation in patient care.</p

Formation of 3-nitrotyrosines in carbonic anhydrase III is a sensitive marker of oxidative stress in skeletal muscle

Oxidation of skeletal muscle proteins has been reported to occur following contractions, with ageing, and with a variety of disease states, but the nature of the oxidised proteins has not been identified. A proteomics approach was utilised to identify major proteins that contain carbonyls and/or 3-nitrotyrosine (3-NT) groups in the gastrocnemius (GTN) muscles of adult (5–11 14months of age) and old (26–28 14months of age) wild type (WT) mice and adult mice lacking copper, zinc superoxide dismutase ( Sod1 −/− mice), manganese superoxide dismutase ( Sod2 +/− mice) or glutathione peroxidase 1 ( GPx1 −/− mice). In quiescent GTN muscles of adult and old WT mice, protein carbonylation and/or formation of 3-NT occurred in several proteins involved in glycolysis, as well as creatine kinase and carbonic anhydrase III. Following contractions, the 3-NT intensity was increased in specific protein bands from GTN muscles of both adult and old WT mice. In quiescent GTN muscles from adult Sod1 −/− , Sod2 +/− or GPx1 −/− mice compared with age-matched WT mice only carbonic anhydrase III showed a greater 3-NT content. We conclude that formation of 3-NT occurs readily in response to oxidative stress in carbonic anhydrase III and this may provide a sensitive measure of oxidative damage to muscle proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56035/1/362_ftp.pd

Seroprevalence of hepatitis B and hepatitis C among blood donors in Sierra Leone: A multi-year retrospective study

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Effect of telecare on use of health and social care services: findings from the Whole Systems Demonstrator cluster randomised trial

Objective: to assess the impact of telecare on the use of social and health care. Part of the evaluation of the Whole Systems Demonstrator trial. Participants and setting: a total of 2,600 people with social care needs were recruited from 217 general practices in three areas in England. Design: a cluster randomised trial comparing telecare with usual care, general practice being the unit of randomisation. Participants were followed up for 12 months and analyses were conducted as intention-to-treat. Data sources: trial data were linked at the person level to administrative data sets on care funded at least in part by local authorities or the National Health Service. Main outcome measures: the proportion of people admitted to hospital within 12 months. Secondary endpoints included mortality, rates of secondary care use (seven different metrics), contacts with general practitioners and practice nurses, proportion of people admitted to permanent residential or nursing care, weeks in domiciliary social care and notional costs. Results: 46.8% of intervention participants were admitted to hospital, compared with 49.2% of controls. Unadjusted differences were not statistically significant (odds ratio: 0.90, 95% CI: 0.75–1.07, P = 0.211). They reached statistical significance after adjusting for baseline covariates, but this was not replicated when adjusting for the predictive risk score. Secondary metrics including impacts on social care use were not statistically significant. Conclusions: telecare as implemented in the Whole Systems Demonstrator trial did not lead to significant reductions in service use, at least in terms of results assessed over 12 months