Surrogacy in invasion research and management: inferring “impact” from “invasiveness”

Biological invasions are widely accepted drivers of biodiversity decline, yet the ecological impacts of invaders in many contexts remain largely unmeasured. Consequently, other measures of a species invasion (e.g. local abundance) are regularly used as surrogates (or ‘proxies’) to infer impact on recipient ecosystems. The use of surrogates for impact represents an implicit application of ecological surrogacy in invasion science, but without the evaluation and validation of surrogate-target relationships that characterizes surrogate use in other fields. While there are practical reasons for this, there also are risks associated with not testing the accuracy, stability and certainty of surrogate-impact relationships that need to be acknowledged. Recognizing the role of surrogacy in invasion science offers previously unappreciated solutions for increasing the quantitative rigor of invasive species impact assessments that inform management decisions.ARC Laureate Fellowshi

Climate change impacts on critical international transportation assets of Caribbean Small Island Developing States (SIDS): the case of Jamaica and Saint Lucia

This contribution presents an assessment of the potential vulnerabilities to climate variability and change (CV & C) of the critical transportation infrastructure of Caribbean Small Island Developing States (SIDS). It focuses on potential operational disruptions and coastal inundation forced by CV & C on four coastal international airports and four seaports in Jamaica and Saint Lucia which are critical facilitators of international connectivity and socioeconomic development. Impact assessments have been carried out under climatic conditions forced by a 1.5 °C specific warming level (SWL) above pre-industrial levels, as well as for different emission scenarios and time periods in the twenty-first century. Disruptions and increasing costs due to, e.g., more frequent exceedance of high temperature thresholds that could impede transport operations are predicted, even under the 1.5 °C SWL, advocated by the Alliance of Small Island States (AOSIS) and reflected as an aspirational goal in the Paris Climate Agreement. Dynamic modeling of the coastal inundation under different return periods of projected extreme sea levels (ESLs) indicates that the examined airports and seaports will face increasing coastal inundation during the century. Inundation is projected for the airport runways of some of the examined international airports and most of the seaports, even from the 100-year extreme sea level under 1.5 °C SWL. In the absence of effective technical adaptation measures, both operational disruptions and coastal inundation are projected to increasingly affect all examined assets over the course of the century

Energy dependence of fission product yields from 235

Under a joint collaboration between TUNL-LANL-LLNL, a set of absolute fission product yield measurements has been performed. The energy dependence of a number of cumulative fission product yields (FPY) have been measured using quasi-monoenergetic neutron beams for three actinide targets, 235U, 238U and 239Pu, between 0.5 and 14.8 MeV. The FPYs were measured by a combination of fission counting using specially designed dual-fission chambers and γ-ray counting. Each dual-fission chamber is a back-to-back ionization chamber encasing an activation target in the center with thin deposits of the same target isotope in each chamber. This method allows for the direct measurement of the total number of fissions in the activation target with no reference to the fission cross-section, thus reducing uncertainties. γ-ray counting of the activation target was performed on well-shielded HPGe detectors over a period of two months post irradiation to properly identify fission products. Reported are absolute cumulative fission product yields for incident neutron energies of 0.5, 1.37, 2.4, 3.6, 4.6, 5.5, 7.5, 8.9 and 14.8 MeV. Preliminary results from thermal irradiations at the MIT research reactor will also be presented and compared to present data and evaluations. This work was performed under the auspices of the U.S. Department of Energy by Los Alamos National Security, LLC under contract DE-AC52-06NA25396, Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344 and by Duke University and Triangle Universities Nuclear Laboratory through NNSA Stewardship Science Academic Alliance grant No. DE-FG52-09NA29465, DE-FG52-09NA29448 and Office of Nuclear Physics Grant No. DE-FG02-97ER41033

Random DNA fragmentation allows detection of single-copy, single-exon alterations of copy number by oligonucleotide array CGH in clinical FFPE samples

Genomic technologies, such as array comparative genomic hybridization (aCGH), increasingly offer definitive gene dosage profiles in clinical samples. Historically, copy number profiling was limited to large fresh-frozen tumors where intact DNA could be readily extracted. Genomic analyses of pre-neoplastic tumors and diagnostic biopsies are often limited to DNA processed by formalin-fixation and paraffin-embedding (FFPE). We present specialized protocols for DNA extraction and processing from FFPE tissues utilizing DNase processing to generate randomly fragmented DNA. The protocols are applied to FFPE clinical samples of varied tumor types, from multiple institutions and of varied block age. Direct comparative analyses with regression coefficient were calculated on split-sample (portion fresh/portion FFPE) of colorectal tumor samples. We show equal detection of a homozygous loss of SMAD4 at the exon-level in the SW480 cell line and gene-specific alterations in the split tumor samples. aCGH application to a set of archival FFPE samples of skin squamous cell carcinomas detected a novel hemizygous deletion in INPP5A on 10q26.3. Finally we present data on derivative of log ratio, a particular sensitive detector of measurement variance, for 216 sequential hybridizations to assess protocol reliability over a wide range of FFPE samples

Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain

TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis - known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions

Mixed methods study protocol for combining stakeholder-led rapid evaluation with near real-time continuous registry data to facilitate evaluations of quality of care in intensive care units [version 1; peer review: awaiting peer review]

BACKGROUND: Improved access to healthcare in low- and middle-income countries (LMICs) has not equated to improved health outcomes. Absence or unsustained quality of care is partly to blame. Improving outcomes in intensive care units (ICUs) requires delivery of complex interventions by multiple specialties working in concert, and the simultaneous prevention of avoidable harms associated with the illness and the treatment interventions. Therefore, successful design and implementation of improvement interventions requires understanding of the behavioural, organisational, and external factors that determine care delivery and the likelihood of achieving sustained improvement. We aim to identify care processes that contribute to suboptimal clinical outcomes in ICUs located in LMICs and to establish barriers and enablers for improving the care processes. METHODS: Using rapid evaluation methods, we will use four data collection methods: 1) registry embedded indicators to assess quality of care processes and their associated outcomes; 2) process mapping to provide a preliminary framework to understand gaps between current and desired care practices; 3) structured observations of processes of interest identified from the process mapping and; 4) focus group discussions with stakeholders to identify barriers and enablers influencing the gap between current and desired care practices. We will also collect self-assessments of readiness for quality improvement. Data collection and analysis will be performed in parallel and through an iterative process across eight countries: Kenya, India, Malaysia, Nepal, Pakistan, South Africa, Uganda and Vietnam. CONCLUSIONS: The results of our study will provide essential information on where and how care processes can be improved to facilitate better quality of care to critically ill patients in LMICs; thus, reduce preventable mortality and morbidity in ICUs. Furthermore, understanding the rapid evaluation methods that will be used for this study will allow other researchers and healthcare professionals to carry out similar research in ICUs and other health services

Using a Delphi process to determine optimal care for patients with pancreatic cancer

Aim Overall 5-year survival for pancreatic cancer is ~5%. Optimising the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. Methods Using a Delphi process, a multi-disciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one (no importance/disagree) to 10 (very important/agree) the factors. The mean and coefficient of variation scores were calculated and categorised into three levels of importance. Results Overall 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from 9 disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multi-disciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and inter- disciplinary variation in views about MDT membership and roles. Conclusion Overall the opinions of Australian health professionals reflect international guideline recommended care; however they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multi-disciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America