Marketing a tourism industry in late stage decline: The case of the Isle of Man

Qualitative interviews in the Isle of Man uncovered local perceptions of a tourism industry in late stage decline. Social impacts of decline are pronounced including facilities loss, cultural changes and a heightening of perceived peripherality: which taken together undermine local identity. Tourists are welcomed as they help to affirm the pride residents have in their island in creating a more active atmosphere, provide social interaction opportunities and to combat negative stereotyping. Thus findings emphasise the diverse, unique and persistent benefits of tourism in the Isle of Man, despite its decline. Destination marketing recommendations are therefore made to better address the experiences and desires of communities experiencing decline

A three-arm randomised phase II study of the MEK inhibitor selumetinib alone or in combination with paclitaxel in metastatic uveal melanoma

\ua9 2024 The AuthorsAims: The MAPK pathway is constitutively activated in uveal melanoma (UM). Selumetinib (AZD6244, ARRY-142886), a MEK inhibitor, has shown limited activity as monotherapy in metastatic UM. Pre-clinical studies support synergistic cytotoxic activity for MEK inhibitors combined with taxanes, and here we sought to assess the clinical efficacy of combining selumetinib and paclitaxel. Patients and methods: Seventy-seven patients with metastatic UM who had not received prior chemotherapy were randomised to selumetinib alone, or combined with paclitaxel with or without interruption in selumetinib two days before paclitaxel. The primary endpoint was progression free survival (PFS). After amendment, the combination arms were combined for analysis and the sample size adjusted to detect a hazard ratio (HR): 0.55, 80% power at 1-sided 5% significance level. Results: The median PFS in the combination arms was 4.8 months (95% CI: 3.8 - 5.6) compared with 3.4 months (2.0 - 3.9) in the selumetinib arm (HR 0.62 [90% CI 0.41 - 0.92], 1-sided p-value = 0.022). ORR was 14% and 4% in the combination and monotherapy arms respectively. Median OS was 9 months for the combination and was not significantly different from selumetinib alone (10 months) with HR of 0.98 [90% CI 0.58 - 1.66], 1-sided p-value = 0.469. Toxicity was in keeping with the known profiles of the agents involved. Conclusions: SelPac met its primary endpoint, demonstrating an improvement in PFS for combination selumetinib and paclitaxel. No improvement in OS was observed, and the modest improvement in PFS is not practice changing

Optimal Duration and Timing of Adjuvant Chemotherapy After Definitive Surgery for Ductal Adenocarcinoma of the Pancreas: Ongoing Lessons From the ESPAC-3 Study

n/

Evaluation of a primary care-based collaborative care model (PARTNERS2) for people with diagnoses of schizophrenia, bipolar, or other psychoses: study protocol for a cluster randomised controlled trial

YesCurrent NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses.PARTNERS2 is funded by the National Institute for Health Research (NIHR) under its Programme Grant for Applied Research Programme (grant number: RP-PG- 200625). This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust

The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer

BACKGROUND: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease. METHODS: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Group for Pancreatic Cancer randomised controlled trials. Analyses were carried out to assess the association between clinical characteristics and the presence of preoperative diabetes, as well as the effect of diabetic status on overall survival. RESULTS: In total, 1105 patients were included in the analysis, of whom 257 (23%) had confirmed diabetes and 848 (77%) did not. Median (95% confidence interval (CI)) unadjusted overall survival in non-diabetic patients was 22.3 (20.8–24.1) months compared with 18.8 (16.9–22.1) months for diabetic patients (P=0.24). Diabetic patients were older, had increased weight and more co-morbidities. Following adjustment, multivariable analysis demonstrated that diabetic patients had an increased risk of death (hazard ratio: 1.19 (95% CI 1.01, 1.40), P=0.034). Maximum tumour size of diabetic patients was larger at randomisation (33.6 vs 29.7 mm, P=0.026). CONCLUSIONS: Diabetes mellitus was associated with increased tumour size and reduced survival following pancreatic cancer resection and adjuvant chemotherapy

The nighttime distribution of ozone in the low-latitude mesosphere

The intensity of stars at wavelengths in the Hartley continuum region of ozone has been monitored by the University of Wisconsin stellar photometers aboard the OAO-2 satellite during occultation of the star by the earth's atmosphere. These occultation data have been used to determine the ozone number density profile at the occultation tangent point. The nighttime ozone number density profile has a bulge in its vertical profile with a peak of 1 to 3×10 8 cm −3 at approximately 83 km and a minimum near 75 km. The ozone number density at high altitudes varies by as much as a factor of 4, but does not show any clear seasonal variation or nighttime variation. The retrieved ozone number density profiles define a data envelope that is compared with other nighttime observations of the ozone number density profile and also the results of theoretical models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43102/1/24_2004_Article_BF00881080.pd

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Sedimentary macrofossil records reveal ecological change in English lakes: implications for conservation

Aquatic macrophytes play a key role in providing habitat, refuge and food for a range of biota in shallow lakes. However, many shallow lakes have experienced declines in macrophyte vegetation in recent decades, principally due to eutrophication. As changes in macrophyte composition and abundance can affect overall ecological structure and function of a lake, an assessment of the timing and nature of such changes is crucial to our understanding of the wider lake ecosystem. In the typical absence of historical plant records, the macro-remains of macrophytes preserved in lake sediments can be used to assess long-term changes in aquatic vegetation. We generated recent (150–200 years) plant macrofossil records for six English lakes subject to conservation protection to define past macrophyte communities, assess trajectories of ecological change and consider the implications of our findings for conservation targets and strategies. The data for all six lakes reveal a diverse submerged macrophyte community, with charophytes as a key component, in the early part of the sedimentary records. The stratigraphies indicate considerable change to the aquatic vegetation over the last two centuries with a general shift towards species more typically associated with eutrophic conditions. A common feature is the decline in abundance of low-growing charophytes and an increase in tall canopy-forming angiosperms such as fine-leaved Potamogeton species, Zannichellia palustris and Callitriche species. We hypothesise, based on findings from long-term datasets and palaeoecological records from enriched shallow lakes where plants are now absent, that the observed shifts provide a warning to managers that the lakes are on a pathway to complete macrophyte loss such that nutrient load reduction is urgently needed. It is the sound understanding of present-day plant ecology that affords such reliable interpretation of the fossil data which, in turn, provide valuable context for current conservation decisions