Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years

Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme

Co-opetition models for governing professional football

In recent years, models for co-creating value in a business-to-business context have often been examined with the aim of studying the strategies implemented by and among organisations for competitive and co-operative purposes. The traditional concepts of competition and co-operation between businesses have now evolved, both in terms of the sector in which the businesses operate and in terms of the type of goods they produce. Many researchers have, in recent times, investigated the determinants that can influence the way in which the model of co-opetition can be applied to the football world. Research interest lies in the particular features of what makes a good football. In this paper, the aim is to conduct an analysis of the rules governing the “football system”, while also looking at the determinants of the demand function within football entertainment. This entails applying to football match management the co-opetition model, a recognised model that combines competition and co-operation with the view of creating and distributing value. It can, therefore, be said that, for a spectator, watching sport is an experience of high suspense, and this suspense, in turn, depends upon the degree of uncertainty in the outcome. It follows that the rules ensuring that both these elements can be satisfied are a fertile ground for co-operation between clubs, as it is in the interest of all stakeholders to offer increasingly more attractive football, in comparison with other competing products. Our end purpose is to understand how co-opetition can be achieved within professional football

Performance measures of the specialty referral process: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Performance of specialty referrals is coming under scrutiny, but a lack of identifiable measures impedes measurement efforts. The objective of this study was to systematically review the literature to identify published measures that assess specialty referrals.</p> <p>Methods</p> <p>We performed a systematic review of the literature for measures of specialty referral. Searches were made of MEDLINE and HealthSTAR databases, references of eligible papers, and citations provided by content experts. Measures were eligible if they were published from January 1973 to June 2009, reported on validity and/or reliability of the measure, and were applicable to Organization for Economic Cooperation and Development healthcare systems. We classified measures according to a conceptual framework, which underwent content validation with an expert panel.</p> <p>Results</p> <p>We identified 2,964 potentially eligible papers. After abstract and full-text review, we selected 214 papers containing 244 measures. Most measures were applied in adults (57%), assessed structural elements of the referral process (60%), and collected data via survey (62%). Measures were classified into non-mutually exclusive domains: need for specialty care (N = 14), referral initiation (N = 73), entry into specialty care (N = 53), coordination (N = 60), referral type (N = 3), clinical tasks (N = 19), resource use (N = 13), quality (N = 57), and outcomes (N = 9).</p> <p>Conclusions</p> <p>Published measures are available to assess the specialty referral process, although some domains are limited. Because many of these measures have been not been extensively validated in general populations, assess limited aspects of the referral process, and require new data collection, their applicability and preference in assessment of the specialty referral process is needed.</p

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Computer-assisted mammographic imaging

Computer-assisted mammography imaging comprises computer-based analysis of digitized images resulting in prompts aiding mammographic interpretation and computerized stereotactic localization devices which improve location accuracy. The commercial prompting systems available are designed to draw attention to mammographic abnormalities detected by algorithms based on symptomatic practise in North America. High sensitivity rates are important commercially but result in increased false prompt rates, which are known to distract radiologists. A national shortage of breast radiologists in the UK necessitates evaluation of such systems in a population breast screening programme to determine effectiveness in increasing cancer detection and feasibility of implementation

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P&lt;0.05) and macrophage (P&lt;0.05) infiltration and microvessel density (P&lt;0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P&lt;0.01), negative hormonal receptor (P&lt;0.10), lower albumin concentrations (P&lt;0.01), increased tumour proliferation (P&lt;0.05), increased tumour microvessel density (P&lt;0.05), the extent of locoregional control (P&lt;0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P&lt;0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer

Prediction of outcome in patients with metastatic breast cancer remains problematical. The present study evaluated the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer. The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg l−1) and hypoalbuminaemia (<35 g l−1) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. In total, 96 patients were studied. During follow-up 51 patients died of their cancer. On multivariate analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45–3.52, P<0.001) remained significantly associated with cancer-specific survival. The presence of a systemic inflammatory response (the GPS) appears to be a useful indicator of poor outcome independent of treatment in patients with metastatic breast cancer

Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with $n$ current particles, a new particle is born with instantaneous rate $\lambda_n$ and a particle dies with instantaneous rate $\mu_n$. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics

Structural insights into the production of 3-hydroxypropionic acid by aldehyde dehydrogenase from Azospirillum brasilense

3-Hydroxypropionic acid (3-HP) is an important platform chemical to be converted to acrylic acid and acrylamide. Aldehyde dehydrogenase (ALDH), an enzyme that catalyzes the reaction of 3-hydroxypropionaldehyde (3-HPA) to 3-HP, determines 3-HP production rate during the conversion of glycerol to 3-HP. To elucidate molecular mechanism of 3-HP production, we determined the first crystal structure of a 3-HP producing ALDH, alpha-ketoglutarate-semialdehyde dehydrogenase from Azospirillum basilensis (AbKGSADH), in its apo-form and in complex with NAD(+). Although showing an overall structure similar to other ALDHs, the AbKGSADH enzyme had an optimal substrate binding site for accepting 3-HPA as a substrate. Molecular docking simulation of 3-HPA into the AbKGSADH structure revealed that the residues Asn159, Gln160 and Arg163 stabilize the aldehyde-and the hydroxyl-groups of 3-HPA through hydrogen bonds, and several hydrophobic residues, such as Phe156, Val286, Ile288, and Phe450, provide the optimal size and shape for 3-HPA binding. We also compared AbKGSADH with other reported 3-HP producing ALDHs for the crucial amino acid residues for enzyme catalysis and substrate binding, which provides structural implications on how these enzymes utilize 3-HPA as a substrate