Health economics of targeted intraoperative radiotherapy (TARGIT-IORT) for early breast cancer: a cost-effectiveness analysis in the United Kingdom

Objective: The clinical effectiveness of targeted intraoperative radiotherapy (TARGIT-IORT) has been confirmed in the randomised TARGIT-A (targeted intraoperative radiotherapy-alone) trial to be similar to a several weeks’ course of whole-breast external-beam radiation therapy (EBRT) in patients with early breast cancer. This study aims to determine the cost effectiveness of TARGIT-IORT to inform policy decisions about its wider implementation. Setting TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy. Methods: Cost-utility analysis using decision analytic modelling by a Markov model. A cost-effectiveness Markov model was developed using TreeAge Pro V.2015. The decision analytic model compared two strategies of radiotherapy for breast cancer in a hypothetical cohort of patients with early breast cancer based on the published health state transition probability data from the TARGIT-A trial. Analysis was performed for UK setting and National Health Service (NHS) healthcare payer’s perspective using NHS cost data and treatment outcomes were simulated for both strategies for a time horizon of 10 years. Model health state utilities were drawn from the published literature. Future costs and effects were discounted at the rate of 3.5%. To address uncertainty, one-way and probabilistic sensitivity analyses were performed. Main outcome measures: Quality-adjusted life-years (QALYs). Results: In the base case analysis, TARGIT-IORT was a highly cost-effective strategy yielding health gain at a lower cost than its comparator EBRT. Discounted TARGITIORT and EBRT costs for the time horizon of 10 years were £12 455 and £13 280, respectively. TARGIT-IORT gained 0.18 incremental QALY as the discounted QALYs gained by TARGIT-IORT were 8.15 and by EBRT were 7.97 showing TARGIT-IORT as a dominant strategy over EBRT. Model outputs were robust to one-way and probabilistic sensitivity analyses. Conclusions: TARGIT-IORT is a dominant strategy over EBRT, being less costly and producing higher QALY gain

The hydrology of prehistoric farming systems in a central Arizona ecotone

The prehistoric land use and water management in the semi-arid Southwest was examined. Remote sensing data, geology, hydrology and biology are discussed along with an evaluation of remote sensing contributions, recommendations for applications, and proposed future remote sensing studies

Research productivity and academics' conceptions of research

This paper asks the question: do people with different levels of research productivity and identification as a researcher think of research differently? It discusses a study that differentiated levels of research productivity among English and Australian academics working in research-intensive environments in three broad discipline areas: science, engineering and technology; social science and humanities; and medicine and health sciences. The paper explores the different conceptions of research held by these academics in terms of their levels of research productivity, their levels of research training, whether they considered themselves an active researcher and a member of a research team, and their disciplinary differences

Early-Life Adversity Due to Bereavement and Inflammatory Diseases in the Next Generation: A Population Study in Transgenerational Stress Exposure

Emerging evidence suggests that trauma experienced in childhood has negative transgenerational implications for offspring mental and physical health. We aimed to investigate whether early-life adversity experienced as bereavement is associated with chronic inflammatory health in offspring. The study population included 3 generations of Swedish families with a base population of 453,516 children (generation 3) born in 2001-2012. Exposure was defined as the middle generation's (generation 2) experiencing bereavement in childhood due to the death of a parent (generation 1). Outcomes in generation 3 included 2 diagnoses of inflammatory diseases, including asthma, allergic diseases, eczema, and autoimmune diseases. Survival analysis was used to identify causal pathways, including investigation of mediation by generation 2 mood disorders and socioeconomic status (SES). We found that early-life bereavement experienced by women was associated with early-onset offspring asthma (hazard ratio = 1.15, 95% confidence interval: 1.08, 1.23); mediation analysis revealed that 28%-33% of the association may be mediated by SES and 9%-20% by mood disorders. Early-life bereavement experienced by men was associated with autoimmune diseases in offspring (hazard ratio = 1.31, 95% confidence interval: 1.06, 1.62), with no evidence of mediation. In conclusion, adversity experienced early in life may contribute to an increased risk of inflammatory diseases which is partly mediated by mood disorders and SES

Three steps to data quality

The quality of data in general practice clinical information systems varies enormously. This variability jeopardizes the proposed national strategy for an integrated care records service and the capacity of primary care organisations to respond coherently to the demands of clinical governance and the proposed quality-based general practice contract. This is apparent in the difficulty in automating the audit process and in comparing aggregated data from different practices. In an attempt to provide data of adequate quality to support such operational needs, increasing emphasis is being placed on the standardisation of data recording

Plankton community composition, organic carbon and thorium-234 particle size distributions, and particle export in the Sargasso Sea

Measurements of plankton community composition (eight planktonic groups), particle size-fractionated (10, 20, 53, 70, and 100-μm Nitex screens) distributions of organic carbon (OC) and 234Th, and particle export of OC and 234Th are reported over a seasonal cycle (2006–2007) from the Bermuda Atlantic Time-Series (BATS) site. Results indicate a convergence of the particle size distributions of OC and 234Th during the winter-spring bloom period (January–March, 2007). The observed convergence of these particle size distributions is directly correlated to the depth-integrated abundance of autotrophic pico-eukaryotes (r = 0.97, P \u3c 0.05) and, to a lesser extent, Synechococcus (r = 0.85, P \u3c 0.14). In addition, there are positive correlations between the sediment trap flux of OC and 234Th at 150 m and the depth-integrated abundance of pico-eukaryotes (r = 0.94, P \u3c 0.06 for OC, and r = 0.98, P \u3c 0.05 for 234Th) and Synechococcus (r = 0.95, P \u3c 0.05 for OC, and r = 0.94, P \u3c 0.06 for 234Th). An implication of these observations and recent modeling studies (Richardson and Jackson, 2007) is that, although small in size, pico-plankton may influence large particle export from the surface waters of the subtropical Atlantic

Towards Developing AI Literacy: Three Student Provocations on AI in Higher Education

This article reports the reflections of the co-organisers on a recent AI in Higher Education event which was led by students from the University of Leeds and University College London. While academic communities and experts have contributed significantly to the discourse, students’ perspectives have so far been underrepresented. Three student provocations are shared which provided the focus of the discussions during the event. The student co-authors present future-gazing visions of the impact of AI in higher education and beyond. Our collaborative reflections highlight that whether we are seeking to bring about desirable, AI-empowered futures, or aspiring to evade undesirable consequences of these new technologies, it will be vital to develop and enhance the AI literacy of students and educators alike in order to make use of it ethically, creatively and critically

Exogenously added GPI-anchored tissue inhibitor of matrix metal loproteinase-1 (TIMP-1) displays enhanced and novel biological activities

The family of tissue inhibitors of metalloproteinases (TIMPs) exhibits diverse physiological/biological functions including the inhibition of active matrix metalloproteinases, regulation of proMMP activation, cell growth, and the modulation of angiogenesis. TIMP-1 is a secreted protein that can be detected on the cell surface through its interaction with surface proteins. The diverse biological functions of TIMP-1 are thought to lie, in part, in the kinetics of TIMP-1/MMP/surface protein interactions. Proteins anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, are incorporated into their surface membranes. A GPI anchor was fused to TIMP-1 to generate a reagent that could be added directly to cell membranes and thus focus defined concentrations of TIMP-1 protein on any cell surface independent of protein-protein interaction. Unlike native TIMP-1, exogenously added GPI-anchored TIMP-1 protein effectively blocked release of MMP-2 and MMP-9 from osteosarcoma cells. TIMP-1-GP1 was a more effective modulator of migration and proliferation than TIMP-1. While control hTIMP-1 protein did not significantly affect migration of primary microvascular endothelial cells at the concentrations tested, the GPI-anchored TIMP-1 protein showed a pronounced suppression of endothelial cell migration in response to bFGF. In addition, TIMP-1-GPI was more effective at inducing microvascular endothelial proliferation. In contrast, fibroblast proliferation was suppressed by the agent. Reagents based on this method should assist in the dissection of the protease cascades and activities involved in TIMP biology. Membrane-fixed TIMP-1 may represent a more effective version of the protein for use in therapeutic expression

Mapping the potential use of endectocide-treated cattle to reduce malaria transmission

Treating cattle with endectocide is a longstanding veterinary practice to reduce the load of endo and ectoparasites, but has the potential to be added to the malaria control and elimination toolbox, as it also kills malaria mosquitoes feeding on the animals. Here we used openly available data to map the areas of the African continent where high malaria prevalence in 2-10 year old children coincides with a high density of cattle and high density of the partly zoophilic malaria vector Anopheles arabiensis. That is, mapping the areas where treating cattle with endectocide would potentially have the greatest impact on reducing malaria transmission. In regions of Africa that are not dominated by rainforest nor desert, the map shows a scatter of areas in several countries where this intervention shows potential, including central and eastern sub-Saharan Africa. The savanna region underneath the Sahel in West Africa appears as the climatic block that would benefit to the largest extent from this intervention, encompassing several countries. West Africa currently presents the highest under-10 malaria prevalence and elimination within the next twenty years cannot be contemplated there with currently available interventions alone, making the use of endectocide treated cattle as a complementary intervention highly appealing