Health-related quality of life after treatment for bladder cancer in England

Background Little is known about quality of life after bladder cancer treatment. This common cancer is managed using treatments that can affect urinary, sexual and bowel function. Methods To understand quality of life and inform future care, the Department of Health (England) surveyed adults surviving bladder cancer 1–5 years after diagnosis. Questions related to disease status, co-existing conditions, generic health (EQ-5D), cancer-generic (Social Difficulties Inventory) and cancer-specific outcomes (Functional Assessment of Cancer Therapy—Bladder). Results In total, 673 (54%) patients responded; including 500 (74%) men and 539 (80%) with co-existing conditions. Most respondents received endoscopic treatment (60%), while 92 (14%) and 99 (15%) received radical cystectomy or radiotherapy, respectively. Questionnaire completion rates varied (51–97%). Treatment groups reported ≥1 problem using EQ-5D generic domains (59–74%). Usual activities was the most common concern. Urinary frequency was common after endoscopy (34–37%) and radiotherapy (44–50%). Certain populations were more likely to report generic, cancer-generic and cancer-specific problems; notably those with co-existing long-term conditions and those treated with radiotherapy. Conclusion The study demonstrates the importance of assessing patient-reported outcomes in this population. There is a need for larger, more in-depth studies to fully understand the challenges patients with bladder cancer face

Adoption incentives and environmental policy timing under asymmetric information and strategic firm behaviour

We consider the incentives of a single firm to invest in a cleaner technology under emission quotas and emission taxation. We assume asymmetric information about the firm's cost of employing the new technology. Policy is set either before the firm invests (commitment) or after (time consistency). Contrary to conventional wisdom, we find that with commitment (time consistency), quotas give higher (lower) investment incentives than taxes. With quotas (taxes), commitment generally leads to higher (lower) welfare than time consistency. Under commitment with quadratic abatement costs and environmental damages, a modified Weitzman rule applies and quotas usually lead to higher welfare than taxes

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

The mechanism underlying persistent hepatitis B virus (HBV) infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively), were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-β1) were found in sera from persistently infected HBV patients. TGF-β1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-β1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-β1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT) patients. We conclude that TGF-β1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection

Impacts of an Invasive Snail (Tarebia granifera) on Nutrient Cycling in Tropical Streams: The Role of Riparian Deforestation in Trinidad, West Indies

Non-native species and habitat degradation are two major catalysts of environmental change and often occur simultaneously. In freshwater systems, degradation of adjacent terrestrial vegetation may facilitate introduced species by altering resource availability. Here we examine how the presence of intact riparian cover influences the impact of an invasive herbivorous snail, Tarebia granifera, on nitrogen (N) cycling in aquatic systems on the island of Trinidad. We quantified snail biomass, growth, and N excretion in locations where riparian vegetation was present or removed to determine how snail demographics and excretion were related to the condition of the riparian zone. In three Neotropical streams, we measured snail biomass and N excretion in open and closed canopy habitats to generate estimates of mass- and area-specific N excretion rates. Snail biomass was 2 to 8 times greater and areal N excretion rates ranged from 3 to 9 times greater in open canopy habitats. Snails foraging in open canopy habitat also had access to more abundant food resources and exhibited greater growth and mass-specific N excretion rates. Estimates of ecosystem N demand indicated that snail N excretion in fully closed, partially closed, and open canopy habitats supplied 2%, 11%, and 16% of integrated ecosystem N demand, respectively. We conclude that human-mediated riparian canopy loss can generate hotspots of snail biomass, growth, and N excretion along tropical stream networks, altering the impacts of an invasive snail on the biogeochemical cycling of N

Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors

BACKGROUND: Mutations in the c-KIT proto-oncogene have been implicated in the progression of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs) in canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon 17, which encodes a portion of its kinase domain. In contrast, deletions and internal tandem duplication (ITD) mutations are found in the juxtamembrane domain of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations are significantly associated with aberrant KIT protein localization in canine MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT mutations, suggesting that other mutations or other factors may be responsible for aberrant KIT localization in these tumors. METHODS: In order to characterize the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase domain in canine MCTs exons 16–20 of 33 canine MCTs from 33 dogs were amplified and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17 are responsible for aberrant KIT localization in MCTs that lack juxtamembrane domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT mutations. RESULTS: No mutations or polymorphisms were identified in exons 16–20 of any of the MCTs examined. CONCLUSION: In conclusion, mutations in the phospho-transferase portion of c-KIT's kinase domain do not play an important role in the progression of canine cutaneous MCTs, or in the aberrant localization of KIT in canine MCTs

Multiple high-reward items can be prioritized in working memory but with greater vulnerability to interference

An emerging literature indicates that working memory and attention interact in determining what is retained over time, though the nature of this relationship and the impacts on performance across different task contexts remain to be mapped out. In the present study, four experiments examined whether participants can prioritize one or more ‘high reward’ items within a four-item target array for the purposes of an immediate cued recall task, and the extent to which this mediates the disruptive impact of a post-display to-be-ignored suffix. All four experiments indicated that endogenous direction of attention towards high-reward items results in their improved recall. Furthermore, increasing the number of high-reward items from 1 to 3 (Experiments 1-3) produces no decline in recall performance for those items, while associating each item in an array with a different reward value results in correspondingly graded levels of recall performance (Experiment 4). These results suggest the ability to exert precise voluntary control in the prioritization of multiple targets. However, in line with recent outcomes drawn from serial visual memory, this endogenously driven focus on high-reward items results in greater susceptibility to exogenous suffix interference, relative to low-reward items. This contrasts with outcomes from cueing paradigms, indicating that different methods of attentional direction may not always result in equivalent outcomes on working memory performance

Feasibility test of a UK-scalable electronic system for regular collection of patient-reported outcome measures and linkage with clinical cancer registry data: The electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system

<p>Abstract</p> <p>Background</p> <p>Cancer survivors can face significant physical and psychosocial challenges; there is a need to identify and predict which survivors experience what sorts of difficulties. As highlighted in the UK National Cancer Survivorship Initiative, routine post-diagnostic collection of patient reported outcome measures (PROMs) is required; to be most informative, PROMs must be linked and analysed with patients' diagnostic and treatment information. We have designed and built a potentially cost-efficient UK-scalable electronic system for collecting PROMs via the internet, at regular post-diagnostic time-points, for linking these data with patients' clinical data in cancer registries, and for electronically managing the associated patient monitoring and communications; the electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system. This study aims to test the feasibility of the ePOCS system, by running it for 2 years in two Yorkshire NHS Trusts, and using the Northern and Yorkshire Cancer Registry and Information Service.</p> <p>Methods/Design</p> <p>Non-metastatic breast, colorectal and prostate cancer patients (largest survivor groups), within 6 months post-diagnosis, will be recruited from hospitals in the Yorkshire Cancer Network. Participants will be asked to complete PROMS, assessing a range of health-related quality-of-life outcomes, at three time-points up to 15 months post-diagnosis, and subsequently to provide opinion on the ePOCS system via a feedback questionnaire. Feasibility will be examined primarily in terms of patient recruitment and retention rates, the representativeness of participating patients, the quantity and quality of collected PROMs data, patients' feedback, the success and reliability of the underpinning informatics, and the system running costs. If sufficient data are generated during system testing, these will be analysed to assess the health-related quality-of-life outcomes reported by patients, and to explore if and how they relate to disease, treatment and/or individual differences characteristics.</p> <p>Discussion</p> <p>There is currently no system in the UK for collecting PROMs online and linking these with patients' clinical data in cancer registries. If feasible, ePOCS has potential to provide an affordable UK-scalable technical platform to facilitate and support longitudinal cohort research, and improve understanding of cancer survivors' experiences. Comprehensive understanding of survivorship difficulties is vital to inform the development and provision of supportive services and interventions.</p