False‐negative detections from environmental DNA collected in the presence of large numbers of killer whales (Orcinus orca)

While environmental DNA (eDNA) is becoming increasingly established in biodiversity monitoring of freshwater ecosystems, the use of eDNA surveys in the marine environment is still in its infancy. Here, we use two approaches: targeted quantitative PCR (qPCR) and whole-genome enrichment capture followed by shotgun sequencing in an effort to amplify killer whale DNA from seawater samples. Samples were collected in close proximity to killer whales in inshore and offshore waters, in varying sea conditions and from the surface and subsurface but none returned strongly positive detections of killer whale eDNA. We validated our laboratory methodologies by successfully amplifying a dilution series of a positive control of killer whale DNA. Furthermore, DNA of Atlantic mackerel, which was present at all sites during sampling, was successfully amplified from the same seawater samples, with positive detections found in ten of the eighteen eDNA extracts. We discuss the various eDNA collection and amplification methodologies used and the abiotic and biotic factors that influence eDNA detection. We discuss possible explanations for the lack of positive killer whale detections, potential pitfalls, and the apparent limitations of eDNA for genetic research on cetaceans, particularly in offshore regions

Emergency medical services knowledge and attitudes about non-heart-beating donors: Effect of an educational intervention

More than 750,000 people die of sudden death each year, and many are potential non-heart-beating donors (NHBDs) for lung transplant. Although critical, the role of emergency medical services (EMS) personnel in assisting with recovery of NHBD lungs has not been studied. The purpose of this study was to assess knowledge of and attitudes about NHBDs among EMS personnel, evaluate the extent to which knowledge and personal experience with organ donation is associated with attitude, and ascertain the effectiveness of an intervention designed to teach EMS professionals about NHBDs

A Synergistic Approach for Evaluating Climate Model Output for Ecological Applications

Increasing concern about the impacts of climate change on ecosystems is prompting ecologists and ecosystem managers to seek reliable projections of physical drivers of change. The use of global climate models in ecology is growing, although drawing ecologically meaningful conclusions can be problematic. The expertise required to access and interpret output from climate and earth system models is hampering progress in utilizing them most effectively to determine the wider implications of climate change. To address this issue, we present a joint approach between climate scientists and ecologists that explores key challenges and opportunities for progress. As an exemplar, our focus is the Southern Ocean, notable for significant change with global implications, and on sea ice, given its crucial role in this dynamic ecosystem. We combined perspectives to evaluate the representation of sea ice in global climate models. With an emphasis on ecologically-relevant criteria (sea ice extent and seasonality) we selected a subset of eight models that reliably reproduce extant sea ice distributions. While the model subset shows a similar mean change to the full ensemble in sea ice extent (approximately 50% decline in winter and 30% decline in summer), there is a marked reduction in the range. This improved the precision of projected future sea ice distributions by approximately one third, and means they are more amenable to ecological interpretation. We conclude that careful multidisciplinary evaluation of climate models, in conjunction with ongoing modeling advances, should form an integral part of utilizing model output. © 2017 Cavanagh, Murphy, Bracegirdle, Turner, Knowland, Corney, Smith, Waluda, Johnston, Bellerby, Constable, Costa, Hofmann, Jackson, Staniland, Wolf-Gladrow, Xavier

Phase I Study of Cetuximab, Irinotecan, and Vandetanib (ZD6474) as Therapy for Patients with Previously Treated Metastastic Colorectal Cancer

BACKGROUND: To determine the maximum tolerated dose (MTD) and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer. METHODS: Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design). Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1β, IL-6, IL-8, TNF-α, SDF1α) were measured before and after treatment. RESULTS: Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea) were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6) and median overall survival was 10.5 months (95% CI, 5.1-20.7). Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%). Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2. CONCLUSIONS: Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination. TRIAL REGISTRATION: Clinicaltrials.gov NCT00436072

What Can a Pilot Congestive Heart Failure Disease Management Program Tell Us about Likely Return on Investment?: A Case Study from a Program Offered to Federal Employees

In 1999, the Blue Cross and Blue Shield Federal Employee Program (FEP) implemented a pilot disease management program to manage congestive heart failure (CHF) among members. The purpose of this project was to estimate the financial return on investment in the pilot CHF program, prior to a full program rollout. A cohort of 457 participants from the state of Maryland was matched to a cohort of 803 nonparticipants from a neighboring state where the CHF program was not offered. Each cohort was followed for 12 months before the program began and 12 months afterward. The outcome measures of primary interest were the differences over time in medical care expenditures paid by FEP and by all payers. Independent variables included indicators of program participation, type of heart disease, comorbidity measures, and demographics. From the perspective of the funding organization (FEP), the estimated return on investment for the pilot CHF disease management program was a savings of $1.08 in medical expenditure for every dollar spent on the program. Adding savings to other payers as well, the return on investment was a savings of$1.15 in medical expenditures per dollar spent on the program. The amount of savings depended upon CHF risk levels. The value of a pilot initiative and evaluation is that lessons for larger-scale efforts can be learned prior to full-scale rollout. (Disease Management 2005;8:346-360)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63402/1/dis.2005.8.346.pd

New technologies to study helminth development and host-parasite interactions

How parasites develop and survive, and how they stimulate or modulate host immune responses are important in understanding disease pathology and for the design of new control strategies. Microarray analysis and bulk RNA sequencing have provided a wealth of data on gene expression as parasites develop through different life-cycle stages and on host cell responses to infection. These techniques have enabled gene expression in the whole organism or host tissue to be detailed, but do not take account of the heterogeneity between cells of different types or developmental stages, nor the spatial organisation of these cells. Single-cell RNA-seq (scRNA-seq) adds a new dimension to studying parasite biology and host immunity by enabling gene profiling at the individual cell level. Here we review the application of scRNA-seq to establish gene expression cell atlases for multicellular helminths and to explore the expansion and molecular profile of individual host cell types involved in parasite immunity and tissue repair. Studying host-parasite interactions in vivo is challenging and we conclude this review by briefly discussing the applications of organoids (stem-cell derived mini-tissues) to examine host-parasite interactions at the local level, and as a potential system to study parasite development in vitro. Organoid technology and its applications have developed rapidly, and the elegant studies performed to date support the use of organoids as an alternative in vitro system for research on helminth parasites

New horizons in geriatric medicine education and training: the need for pan-European education and training standards

The ageing population ought to be celebrated as evidence for the efficacy of modern medicine, but the challenge that this demographic shift presents for 21st century healthcare systems, with increasing numbers of people living with multi-morbidity and frailty, cannot be ignored. There is therefore a need to ensure that all healthcare professionals grasp the basic principles of care of older people. In this paper, we make a case for the development of pan-European education and training standards for the field of geriatric medicine. Firstly, the challenges which face the implementation and delivery of geriatric medicine in a systematic way across Europe are described – these include, but are not limited to; variance in geriatric medicine practice across Europe, insecurity of the specialty in some countries and significant heterogeneity in geriatric medicine training programs across Europe. The opportunities for geriatric medicine are then presented and we consider how engendering core geriatric medicine competencies amongst nongeriatricians has potential to bridge existing gaps in service provision across Europe. Finally, we consider how work can proceed to teach sufficient numbers of doctors and health professionals in the core knowledge, skills and attitudes required to do this. To safeguard the future of the specialty across Europe, we contend that there is a need to strive towards harmonisation of post-graduate geriatric medicine training across Europe, through the establishment of pan-European education and training standards in the specialty