Containing, embracing and hyper-activating Britishness: British-based foreign-owned firms

There are in the UK ownership forms different to the characteristics of Britishness – British-based foreign-owned firms where dominant owners may have differentiated control interests. These may contain, that is, override, national institutional characteristics embedded in a particular national capitalism. Accordingly, separating the agency of these firms from presumed business system structures may reveal how diverse patterns of firm ownership – those associated with British-based foreign-owned firms – can inform dynamic ownership developments in British capitalism which contain and hyper-activate Britishness. The article theorizes British-based foreign-owned firms and provides empirical detail on how ownership characteristics influence financial commitment and strategic control in 10 of these firms

Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity

SNOT-22 in a Control Population

AIM: To assess SNOT-22 and its subscales in a non-rhinosinusitis UK-wide population.  METHODOLOGY/PRINCIPLE: This analysis uses data from the 'Chronic Rhinosinusitis Epidemiology Study' (CRES) which recruited from 30 centres across the UK, and the Socioeconomic Cost of ChrOnic Rhinosinusitis study' (SocCoR); 250 volunteers without CRS were recruited as part of these studies. Study-specific questionnaires including demographics, socioeconomic factors and past medical history as well as SNOT-22 and SF-36 were distributed. The control (non-CRS) population had no self-reported nasal problems in the past, no chronic conditions undergoing active treatment and no hospital admissions in the preceding 12 months.  RESULTS: The mean SNOT-22 total score overall was 12.0. The mean was 10.2 for males with a median of 6.5, and a mean of 13.2 for females with a median of 9. Females scored significantly more highly than males on the sleep/fatigue and facial domains.  CONCLUSIONS: Our data demonstrate differences in SNOT-22 amongst males and females. These data can be used in future studies for comparison with different disease populations with rhinosinusitis. This article is protected by copyright. All rights reserved

Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation

Abstract: Background: The five-tiered Cambridge Prognostic Group (CPG) classification is a better predictor of prostate cancer-specific mortality than the traditional three-tiered classification (low, intermediate, and high risk). We investigated radical treatment rates according to CPG in men diagnosed with non-metastatic prostate cancer in England between 2014 and 2017. Methods: Patients diagnosed with non-metastatic prostate cancer were identified from the National Prostate Cancer Audit database. Men were risk stratified according to the CPG classification. Risk ratios (RR) were estimated for undergoing radical treatment according to CPG and for receiving radiotherapy for those treated radically. Funnel plots were used to display variation in radical treatment rates across hospitals. Results: A total of 61,999 men were included with 10,963 (17.7%) in CPG1 (lowest risk group), 13,588 (21.9%) in CPG2, 9452 (15.2%) in CPG3, 12,831 (20.7%) in CPG4, and 15,165 (24.5%) in CPG5 (highest risk group). The proportion of men receiving radical treatment increased from 11.3% in CPG1 to 78.8% in CGP4, and 73.3% in CPG5. Men in CPG3 were more likely to receive radical treatment than men in CPG2 (66.3% versus 48.4%; adjusted RR 1.44; 95% CI 1.36–1.53; P < 0.001). Radically treated men in CPG3 were also more likely to receive radiotherapy than men in CPG2 (59.2% versus 43.9%; adjusted RR, 1.18; 95% CI 1.10–1.26). Although radical treatment rates were similar in CPG4 and CPG5 (78.8% versus 73.3%; adjusted RR 1.01; 95% CI 0.98–1.04), more men in CPG5 had radiotherapy than men in CPG4 (79.9% versus 59.1%, adjusted RR 1.26; 95% CI 1.12–1.40). Conclusions: The CPG classification distributes men in five risk groups that are about equal in size. It reveals differences in treatment practices in men with intermediate-risk disease (CPG2 and CPG3) and in men with high-risk disease (CPG4 and CPGP5) that are not visible when using the traditional three-tiered risk classification

Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation

Abstract: Background: The five-tiered Cambridge Prognostic Group (CPG) classification is a better predictor of prostate cancer-specific mortality than the traditional three-tiered classification (low, intermediate, and high risk). We investigated radical treatment rates according to CPG in men diagnosed with non-metastatic prostate cancer in England between 2014 and 2017. Methods: Patients diagnosed with non-metastatic prostate cancer were identified from the National Prostate Cancer Audit database. Men were risk stratified according to the CPG classification. Risk ratios (RR) were estimated for undergoing radical treatment according to CPG and for receiving radiotherapy for those treated radically. Funnel plots were used to display variation in radical treatment rates across hospitals. Results: A total of 61,999 men were included with 10,963 (17.7%) in CPG1 (lowest risk group), 13,588 (21.9%) in CPG2, 9452 (15.2%) in CPG3, 12,831 (20.7%) in CPG4, and 15,165 (24.5%) in CPG5 (highest risk group). The proportion of men receiving radical treatment increased from 11.3% in CPG1 to 78.8% in CGP4, and 73.3% in CPG5. Men in CPG3 were more likely to receive radical treatment than men in CPG2 (66.3% versus 48.4%; adjusted RR 1.44; 95% CI 1.36–1.53; P < 0.001). Radically treated men in CPG3 were also more likely to receive radiotherapy than men in CPG2 (59.2% versus 43.9%; adjusted RR, 1.18; 95% CI 1.10–1.26). Although radical treatment rates were similar in CPG4 and CPG5 (78.8% versus 73.3%; adjusted RR 1.01; 95% CI 0.98–1.04), more men in CPG5 had radiotherapy than men in CPG4 (79.9% versus 59.1%, adjusted RR 1.26; 95% CI 1.12–1.40). Conclusions: The CPG classification distributes men in five risk groups that are about equal in size. It reveals differences in treatment practices in men with intermediate-risk disease (CPG2 and CPG3) and in men with high-risk disease (CPG4 and CPGP5) that are not visible when using the traditional three-tiered risk classification

Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters

Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. Patients and methods: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. Results: We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of beta-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of beta-catenin. Analysis of all patients with activating Wnt/beta-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion. Conclusions: The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/beta-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. Clinical Trials.gov Identifier: NCT02022371

Cystatin C: current position and future prospects.

Abstract Cystatin C is a low-molecular-weight protein which has been proposed as a marker of renal function that could replace creatinine. Indeed, the concentration of cystatin C is mainly determined by glomerular filtration and is particularly of interest in clinical settings where the relationship between creatinine production and muscle mass impairs the clinical performance of creatinine. Since the last decade, numerous studies have evaluated its potential use in measuring renal function in various populations. More recently, other potential developments for its clinical use have emerged. This review summarises current knowledge about the physiology of cystatin C and about its use as a renal marker, either alone or in equations developed to estimate the glomerular filtration rate. This paper also reviews recent data about the other applications of cystatin C, particularly in cardiology, oncology and clinical pharmacology. Clin Chem Lab Med 2008;46:1664-86