Importance of Surface Sediments for Reliable 210Pb Dating

Lead-210, 137Cs and 241Am dating techniques have been extensively used in the dating of recent sediments. However, collection of an intact core is the first essential step towards having reliable 210Pb chronologies for the sediments. We collected short gravity cores from Loch Morar, a deep (310 m max. depth), steep-sided lake in Scotland. Lead-210 chronologies for one of the cores did not match with the 137Cs and 241Am records, and the radionuclide data indicate that surface sediments in this core were likely missing. Therefore, sediment chronologies and accumulation rates calculated from unsupported 210Pb activities in the core were deemed unreliable, as confirmed by another core from the same lake. Dating of the cores suggests that sediment dating not only depends on accurate counting of radionuclide activities, but also on the integrity of the cores, in turn determined by sampling location. Importantly, however 210Pb, 137Cs and 241Am data can be carefully assessed to determine the integrity of sediment cores

The ‘Pritchard Trap’: a novel quantitative survey method for crayfish

1. As crayfish invasions continue to threaten native freshwater biota, a detailed understanding of crayfish distribution and population structure becomes imperative. Nonetheless, most current survey methods provide inadequate demographic data. The quantitative ‘Triple Drawdown’ (TDD) dewatering method has highlighted the importance of such data, yet practical constraints prevent its large-scale application. 2. Here, we introduce the ‘Pritchard Trap’, a novel passive sampling method that reliably generates quantitative crayfish population data while requiring substantially lower sampling effort than TDDs. This quadrat-style sampler was extensively tested in headwater streams of North Yorkshire, England, along an invasion gradient for signal crayfish (Pacifastacus leniusculus) from well-established sites to mixed populations of signal crayfish and native white-clawed crayfish (Austropotamobius pallipes). 3. The Pritchard Trap was trialled over several time intervals to determine the minimum required trap deployment time. TDDs at the same sites allowed for a robust evaluation of Pritchard Trap sampling accuracy in representing crayfish densities and population structure. 4. The Pritchard Trap successfully sampled both invasive and native crayfish (8–42 mm carapace length). A minimum passive deployment time of 4 days was required. At low crayfish densities (0.5 individuals m−2), increased trapping effort was necessary to achieve accurate population density and size class distribution estimates. The Pritchard Trap required substantially less sampling effort (working hours) and resources than the TDD, whilst also posing less risk to non-target species. 5. The Pritchard Trap, for the first time, affords logistically simple, truly quantitative investigations of crayfish population demographics for headwater systems. It could be integrated into crayfish research and management, for example to explore density-dependent ecological impacts of invasive crayfish and their management responses or to monitor populations and recruitment in native crayfish conservation initiatives

A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population–Based Observational Data

Objectives To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. Methods All patients newly diagnosed with FL in the UK’s population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. Results Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60–65 million [US$75-80 million], accounting for approximately 10$0.75-2.75 million]. Conclusions Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers

Disease-related factors affecting timely lymphoma diagnosis : a qualitative study exploring patient experiences

Background Expediting cancer diagnosis is widely perceived as one way to improve patient outcomes. Evidence indicates that lymphoma diagnosis is often delayed, yet understanding of issues influencing this is incomplete. Aim To explore patients' and their relatives' perceptions of disease-related factors affecting time to diagnosis of Hodgkin and non-Hodgkin lymphoma. Design and setting Qualitative UK study involving patients with indolent and aggressive lymphomas, and their relatives, from an established population-based cohort in the north of England. Method Semi-structured interviews with 35 patients and 15 of their relatives. Interviews were audiorecorded and transcribed, and qualitative descriptive analysis was undertaken. Results Participant accounts suggest that certain features of lymphoma can impact on patients' and healthcare providers' (HCPs) responses to disease onset. Three characteristics stand out: disease occurrence (rare), manifestation (varied), and investigative options (often inconclusive). Interviewees described how they, and some HCPs, lacked familiarity with lymphoma, seldom considering it a likely explanation for their symptoms. Symptoms reported were highly variable, frequently non-specific, and often initially thought to be associated with various benign, self-limiting causes. Blood tests and other investigations, while frequently able to detect abnormalities, did not reliably indicate malignancy. Interviewees reported the potential for improvements among HCPs in information gathering, communication of uncertainty, and re-presentation advice for non-resolving/ progressive health changes. Conclusion This study demonstrates the complex characteristics of lymphoma, perceived by patients as prolonging time to diagnosis, often despite significant effort by themselves, their relatives, and HCPs to expedite this process. The findings also illustrate why simple solutions to delayed diagnosis of lymphoma are lacking

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG- GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na+/Ca2+ exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies

Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL) : a discrete event simulation model on a UK population-based observational cohort

Background Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL. Methods All patients newly diagnosed with DLBCL in the UK’s population-based Haematological Malignancy Research Network (www.hmrn.org) in 2007 were followed until 2013 (n=271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5% per annum. Results Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2,930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7,376 for first, second, and third line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million. Conclusions This is the first cost modelling study using empirical data to provide ‘real world’ evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine