A consensus on the use of daylight photodynamic therapy in the UK

Background: Actinic keratoses (AKs) are a consequence of chronic exposure to ultraviolet radiation. Treatment of chronically photo-damaged skin and AKs is driven by risk of progression to squamous cell carcinoma, as well as for symptomatic relief. Conventional photodynamic therapy (c-PDT) is indicated when AKs are multiple or confluent and if patients respond poorly or are unable to tolerate other therapies. c-PDT is limited by the field size that can be treated in single sessions and can cause significant discomfort.Objective: Recent studies investigated daylight illumination to activate protoporphyrin IX and daylight-PDT (d-PDT) is now licensed in the UK for face and scalp AKs. A group of experts met to discuss application of d-PDT with methyl aminolevulinate (MAL) and develop a UK consensus statement, specific to UK weather conditions.Methods: The UK consensus recommendations were reached among eight experts, who reviewed recent studies on d-PDT, assessed UK meteorological data and discussed personal experiences of d-PDT for AKs.Results: Recommendations from these discussions provide guidance on d-PDT use, specifically regarding patient selection, therapeutic indications, when to treat, skin preparation, MAL application and daylight exposure for patients with AKs.Conclusions: This UK expert consensus provides practical guidance for UK application of d-PDT

Public health outcome of Tuberculosis Cluster Investigations, England 2010–2013

Objectives: Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB straintyped (ST) clusters. Methods: A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. Results: There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. Conclusions: We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients.This work was funded by CHDI Inc. (A.J.M), and supported in part by a UK Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/I019405/1 (D.J.S). D.J.S. is a Royal Society Wolfson Research Merit Award Holder

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Freedom of choice to migrate: adaptation to climate change in Bangladesh

Adaptation is an essential part of climate change policy. In areas where impacts are likely to be severe, migration is considered to be an adaptation option. In Bangladesh coastal areas migration due to climate change is contingent on people’s freedom of choice at individual and household level. Following Amartya Sen’s capability approach, we argue that there should be a line drawn between migrations by free choice versus forced migration. Sen’s capability approach focuses on the importance of people’s freedom of choice to act, and the ability to achieve what they consider valuable in their life. In this paper, we use an extensive empirical work engaging 22 focus groups discussions (8–12 individuals in each group) and 14 Key Informants Interviews in South-West Bangladesh to elicit how freedom of choice changes with the economic class and social status of an individual. Using these data we apply Sen’s capability approach to understand the role of the freedom of choice when considering migration as an adaptation option. We argue that the capability approach is essential in revealing a thin border between migration as a (planned) adaptation option and forced migration