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\"'Essential reading for any young actor' Dame Maggie SmithCompetition for acting work is fierce and talent is not necessarily enough. Actors need all the help they can get with all aspects of the profession. Now in its fifth edition, completely revised and updated, this practical, comprehensive guide contains invaluable information and advice to enable actors to succeed in the business. Written with honesty, humour and thoroughness, An Actor's Guide to Getting Work draws on the author's rich experience in the field to offer advice to both the novice and the seasoned performer. New material in this fifth edition includes what drama schools are looking for, approaching Shakespeare for audition, professional email etiquette, using the internet as a self-marketing tool, and many more useful checklists and updated insights into the profession.

Abstract The glycation gap (GGap) and the similar hemoglobin glycation index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose, respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being >1 U of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices and explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and HGI are associated with variation in risk of complications and mortality and demonstrate the potential for clinical error in the unquestioning use of HbA1c. We explore the underlying etiology of the variation of HbA1c from mean glucose in blood plasma, including the potential role of enzymatic deglycation of hemoglobin by fructosamine-3-kinase. We conclude that measurement of GGap and HGI are important to diabetes clinicians and their patients in individualization of therapy and the avoidance of harm arising from consequent inappropriate assessment of glycemia and use of therapies.

ObjectivesThe objective of this study was to describe variations in COVID-19 outcomes in relation to local risks within a well-defined but diverse single-city area.DesignObservational study of COVID-19 outcomes using quality-assured integrated data from a single UK hospital contextualised to its feeder population and associated factors (comorbidities, ethnicity, age, deprivation).Setting/participantsSingle-city hospital with a feeder population of 228 632 adults in Wolverhampton.Main outcome measuresHospital admissions (defined as COVID-19 admissions (CA) or non-COVID-19 admissions (NCA)) and mortality (defined as COVID-19 deaths or non-COVID-19 deaths).ResultsOf the 5558 patients admitted, 686 died (556 in hospital); 930 were CA, of which 270 were hospital COVID-19 deaths, 47 non-COVID-19 deaths and 36 deaths after discharge; of the 4628 NCA, there were 239 in-hospital deaths (2 COVID-19) and 94 deaths after discharge. Of the 223 074 adults not admitted, 407 died. Age, gender, multimorbidity and black ethnicity (OR 2.1 (95% CI 1.5 to 3.2), p<0.001, compared with white ethnicity, absolute excess risk of <1/1000) were associated with CA and mortality. The South Asian cohort had lower CA and NCA, lower mortality compared with the white group (CA, 0.5 (0.3 to 0.8), p<0.01; NCA, 0.4 (0.3 to 0.6), p<0.001) and community deaths (0.5 (0.3 to 0.7), p<0.001). Despite many common risk factors for CA and NCA, ethnic groups had different admission rates and within-group differing association of risk factors. Deprivation impacted only the white ethnicity, in the oldest age bracket and in a lesser (not most) deprived quintile.ConclusionsWolverhampton’s results, reflecting high ethnic diversity and deprivation, are similar to other studies of black ethnicity, age and comorbidity risk in COVID-19 but strikingly different in South Asians and for deprivation. Sequentially considering population and then hospital-based NCA and CA outcomes, we present a complete single health economy picture. Risk factors may differ within ethnic groups; our data may be more representative of communities with high Black, Asian and minority ethnic populations, highlighting the need for locally focused public health strategies. We emphasise the need for a more comprehensible and nuanced conveyance of risk.

The glycation gap (GGap) and the similar hemoglobin glycation index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose, respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being >1 U of glycated Hb[A.sub.lc]% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices and explain how they can be calculated and that they are not spurious, being consistent in individuals over time. We evaluate the evidence that GGap and HGI are associated with variation in risk of complications and mortality and demonstrate the potential for clinical error in the unquestioning use of Hb[A.sub.lc]. We explore the underlying etiology of the variation of Hb[A.sub.lc] from mean glucose in blood plasma, including the potential role of enzymatic deglycation of hemoglobin by fructosamine-3-kinase. We conclude that measurement of GGap and HGI are important to diabetes clinicians and their patients in individualization of therapy and the avoidance of harm arising from consequent inappropriate assessment of glycemia and use of therapies. (Endocrine Reviews 40: 988 - 999, 2019)

Aquaporins are membrane proteins that regulate cellular water flow. Recently, aquaporins have been proposed as mediators of cancer cell biology. A subset of aquaporins, referred to as aquaglyceroporins are known to facilitate the transport of glycerol. The present study describes the effect of gene knockdown of the aquaglyceroporin AQP3 on MDA-MB-231 breast cancer cell proliferation, migration, invasion, adherence and response to the chemotherapeutic agent 5-fluorouracil. shRNA mediated AQP3 gene knockdown induced a 28% reduction in cellular proliferation (P<0.01), a 39% decrease in migration (P<0.0001), a 24% reduction in invasion (P<0.05) and a 25% increase in cell death at 100 µM 5-FU (P<0.01). Analysis of cell permeability to water and glycerol revealed that MDA-MB-231 cells with knocked down AQP3 demonstrated a modest decrease in water permeability (17%; P<0.05) but a more marked decrease in glycerol permeability (77%; P<0.001). These results suggest that AQP3 has a role in multiple aspects of breast cancer cell pathophysiology and therefore represents a novel target for therapeutic intervention.

The glycaemic index (GI) is used to demonstrate the tendency of foods to increase blood glucose and is thus an important characteristic of newly formulated foods to tackle the rising prevalence of diabetics and associated diseases. The GI of gluten-free biscuits formulated with alternate flours, resistant starch and sucrose replacers was determined using in vivo methods with human subjects. The relationship between in vivo GI values and the predicted glycaemic index (pGI) from the in vitro digestibility-based protocols, generally used by researchers, was established. The in vivo data showed a gradual reduction in GI with increased levels of sucrose substitution by maltitol and inulin with biscuits where sucrose was fully replaced, showing the lowest GI of 33. The correlation between the GI and pGI was food formulation-dependent, even though GI values were lower than the reported pGI. Applying a correction factor to pGI tend to close the gap between the GI and pGI for some formulations but also causes an underestimation of GI for other samples. The results thus suggest that it may not be appropriate to use pGI data to classify food products according to their GI.

Now in its fifth edition, An Actor's Guide to Getting Work is an invaluable book which continues to provide students and young actors with an insider's advice to equip them for the cut-throat world of professional theatre. This new edition has been thoroughly updated to incorporate current trends and practices in the industry.

IntroductionCigarette smoking and oxidative stress are common risk factors for the multi-morbidities associated with chronic obstructive pulmonary disease (COPD). Elevated levels of advanced glycation endproducts (AGE) increase the risk of cardiovascular disease (CVD) comorbidity and mortality. The enzyme fructosamine-3-kinase (FN3K) reduces this risk by lowering AGE levels.MethodsThe distribution and expression of FN3K protein in lung tissues from stable COPD and control subjects, as well as an animal model of COPD, was assessed by immunohistochemistry. Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin. Genetic variants within the FN3K and FN3K-RP genes were evaluated for associations with cardiorespiratory function in the Subpopulations and Intermediate Outcome Measures in COPD Study cohort.ResultsThis pilot study demonstrates that FN3K expression in the blood and human lung epithelium is distributed at either high or low levels irrespective of disease status. The percentage of lung epithelial cells expressing FN3K was higher in control smokers with normal lung function, but this induction was not observed in COPD patients nor in a smoking model of COPD. The top five nominal FN3K polymorphisms with possible association to decreased cardiorespiratory function (p<0.008–0.02), all failed to reach the threshold (p<0.0028) to be considered highly significant following multi-comparison analysis. Metformin enhanced systemic levels of FN3K in COPD subjects independent of their high-expression or low-expression status.DiscussionThe data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.