Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

Background: Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients. Methods: Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS). Results: Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide. Conclusion: Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment

Dementia risk in a diverse population: A single-region nested case-control study in the East End of London

Background: Most evidence about dementia risk comes from relatively affluent people of White European ancestry. We aimed to determine the association between ethnicity, area level socioeconomic deprivation and dementia risk, and the extent to which variation in risk might be attributable to known modifiable clinical risk factors and health behaviours. Methods: In this nested case-control study, we analysed data from primary care medical records of a population of 1,016,277 from four inner East London boroughs, United Kingdom, collected between 2009 and 2018. The outcome measures were odds ratios for dementia according to ethnicity and deprivation, before and after the addition of major modifiable risk factors for dementia; and weighted population attributable risk for comparison between individual risk factors. Findings: We identified 4137 dementia cases and 15,754 matched controls (mean age for cases and controls were 80·7 years, (SD 8·7); 81·3 years, (SD 8·9) respectively, range 27–103). Black and South Asian ethnicity were both associated with increased risk of dementia relative to White (odds ratios [95% CI]: Black 1·43 [1·31–1·56]; South Asian 1.17 [1·06–1·29]). Area-level deprivation was independently associated with an increased risk of dementia in a dose-dependent manner. Black and South Asian ethnicity were both associated with a younger age at dementia diagnosis (odds ratios [95%CI]: 0·70 [0·61–0·80] and 0·55 [0·47–0·65], respectively). Population attributable risk was higher for ethnicity (9·7%) and deprivation (11·7%) than for any established modifiable risk factor in this population. Interpretation: Ethnicity and area-level deprivation are independently associated with dementia risk in East London. This effect may not be attributable to the effect of known risk factors

PHOTOSTENT-02: porfimer sodium photodynamic therapy plus stenting versus stenting alone in patients with locally advanced or metastatic biliary tract cancer

Background: Endobiliary stenting is standard practice for palliation of obstructive jaundice due to biliary tract cancer (BTC). Photodynamic therapy (PDT) may also improve biliary drainage and previous small studies suggested survival benefit. // Aims: To assess the difference in outcome between patients with BTC undergoing palliative stenting plus PDT versus stenting alone. // Methods: 92 patients with confirmed locally advanced or metastatic BTC, ECOG performance status 0–3 and adequate biliary drainage were randomised (46 per group) to receive porfimer sodium PDT plus stenting or stenting alone. The primary end point was overall survival (OS). Toxicity and progression-free survival (PFS) were secondary end points. Treatment arms were well balanced for baseline factors and prior therapy. // Results: No significant differences in grade 3–4 toxicities and no grade 3–4 adverse events due to PDT were observed. Thirteen (28%) PDT patients and 24 (52%) stent alone patients received subsequent palliative chemotherapy. After a median follow-up of 8.4 months, OS and PFS were worse in patients receiving PDT compared with stent alone group (OS median 6.2 vs 9.8 months (HR 1.56, 95% CI 1.00 to 2.43, p=0.048) and PFS median 3.4 vs 4.3 months (HR 1.43, 95% CI: 0.93 to 2.18, p=0.10), respectively). // Conclusion: In patients with locally advanced or metastatic BTC, PDT was associated with worse outcome than stenting alone, explained only in part by the differences in chemotherapy treatments. We conclude that optimal stenting remains the treatment of choice for malignant biliary obstruction and the use of PDT for this indication cannot be recommended outside of clinical trials. // Trial registration number: ISRCTN 87712758; EudraCT 2005-001173-96; UKCRN ID: 1461

The National Plant Monitoring Scheme: a technical review

The National Plant Monitoring Scheme, coordinated by the Botanical Society of Britain and Ireland, the Centre for Ecology & Hydrology, JNCC and Plantlife, was launched in 2015 to provide an indication of the status and trends of plants and semi-natural habitats across the UK. The scheme is based on volunteer recording according to a set protocol at pre-determined monads selected through a weighted-random sampling scheme

The design, launch and assessment of a new volunteer-based plant monitoring scheme for the United Kingdom

Volunteer-based plant monitoring in the UK has focused mainly on distribution mapping; there has been less emphasis on the collection of data on plant communities and habitats. Abundance data provide different insights into ecological pattern and allow for more powerful inference when considering environmental change. Abundance monitoring for other groups of organisms is well-established in the UK, e.g. for birds and butterflies, and conservation agencies have long desired comparable schemes for plants. We describe a new citizen science scheme for the UK (the ‘National Plant Monitoring Scheme’; NPMS), with the primary aim of monitoring the abundance of plants at small scales. Scheme development emphasised volunteer flexibility through scheme co-creation and feedback, whilst retaining a rigorous approach to design. Sampling frameworks, target habitats and species, field methods and power are all described. We also evaluate several outcomes of the scheme design process, including: (i) landscape-context bias in the first two years of the scheme; (ii) the ability of different sets of indicator species to capture the main ecological gradients of UK vegetation; and, (iii) species richness bias in returns relative to a professional survey. Survey rates have been promising (over 60% of squares released have been surveyed), although upland squares are under-represented. Ecological gradients present in an ordination of an independent, unbiased, national survey were well-represented by NPMS indicator species, although further filtering to an entry-level set of easily identifiable species degraded signal in an ordination axis representing succession and disturbance. Comparison with another professional survey indicated that different biases might be present at different levels of participation within the scheme. Understanding the strengths and limitations of the NPMS will guide development, increase trust in outputs, and direct efforts for maintaining volunteer interest, as well as providing a set of ideas for other countries to experiment with

The environmental effectiveness of the Higher Level Stewardship scheme; resurveying the baseline agreement monitoring sample to quantify change between 2009 and 2016. Full technical final report

Agri-environment schemes (AES) are one of the most significant mechanism for delivering environmental policy within England, both in terms of expenditure and coverage of land. AES are multi-objective, primarily addressing conservation of wildlife, landscapes and the historic environment and providing public access as well as addressing broader environmental issues such as climate change and flood management. This project contributes to evaluation of the Higher Level Stewardship (HLS) AES, which was designed to achieve the highest standards of environmental management and target features of the greatest conservation value, including Sites of Special Scientific Interest (SSSIs). Monitoring is a key element of scheme delivery in order to assess the efficacy of AES, and determine which factors contribute to successful AES outcomes. Here, we resurveyed a sample of HLS agreements (surveyed 6-7 years previously), to assess environmental outcomes and in particular change in plant communities over time in relation to AES management. The assessment of change over time allowed the effects of AES management to be quantified against defined objectives, as opposed to drawing conclusions from a single assessment where the conservation value of land entered into an AES can be confounded with AES management effects

Pollinator monitoring more than pays for itself

1. Resilient pollination services depend on sufficient abundance of pollinating insects over time. Currently, however, most knowledge about the status and trends of pollinators is based on changes in pollinator species richness and distribution only. 2. Systematic, long‐term monitoring of pollinators is urgently needed to provide baseline information on their status, to identify the drivers of declines and to inform suitable response measures. 3. Power analysis was used to determine the number of sites required to detect a 30% change in pollinator populations over 10 years. We then evaluated the full economic costs of implementing four national monitoring schemes in the UK: (a) professional pollinator monitoring, (b) professional pollination service monitoring, (c) volunteer collected pan traps and (d) volunteer focal floral observations. These costs were compared to (a) the costs of implementing separate, expert‐designed research and monitoring networks and (b) the economic benefits of pollination services threatened by pollinator loss. 4. Estimated scheme costs ranged from £6,159/year for a 75‐site volunteer focal flower observation scheme to £2.7 M/year for an 800‐site professional pollination service monitoring network. The estimated research costs saved using the site network as research infrastructure range from £1.46–4.17 M/year. The economic value of UK crop yield lost following a 30% decline in pollinators was estimated at ~£188 M/year. 5. Synthesis and applications. We evaluated the full costs of running pollinator monitoring schemes against the economic benefits to research and society they provide. The annual costs of monitoring are <0.02% of the economic value of pollination services that would be lost after a 30% decline in pollination services. Furthermore, by providing high‐quality scientific data, monitoring schemes would save at least £1.5 on data collection per £1 spent. Our findings demonstrate that long‐term systematic monitoring can be a cost‐effective tool for both answering key research questions and setting action points for policymakers. Careful consideration must be given to scheme design, the logistics of national‐scale implementation and resulting data quality when selecting the most appropriate combination of surveyors, methods and site networks to deliver a successful scheme

Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

Background In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. Methods/design This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. Discussion In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial. Trial registration Clinical trial identifier BACCHUS: NCT0165042