Computed tomography-based radiomic markers are independent prognosticators of survival in advanced laryngeal cancer: a pilot study.

OBJECTIVE: Advanced laryngeal cancers are clinically complex; there is a paucity of modern decision-making models to guide tumour-specific management. This pilot study aims to identify computed tomography-based radiomic features that may predict survival and enhance prognostication. METHODS: Pre-biopsy, contrast-enhanced computed tomography scans were assembled from a retrospective cohort (n = 72) with advanced laryngeal cancers (T3 and T4). The LIFEx software was used for radiomic feature extraction. Two features: shape compacity (irregularity of tumour volume) and grey-level zone length matrix - grey-level non-uniformity (tumour heterogeneity) were selected via least absolute shrinkage and selection operator-based Cox regression and explored for prognostic potential. RESULTS: A greater shape compacity (hazard ratio 2.89) and grey-level zone length matrix - grey-level non-uniformity (hazard ratio 1.64) were significantly associated with worse 5-year disease-specific survival (p < 0.05). Cox regression models yielded a superior C-index when incorporating radiomic features (0.759) versus clinicopathological variables alone (0.655). CONCLUSIONS: Two radiomic features were identified as independent prognostic biomarkers. A multi-centre prospective study is necessary for further exploration. Integrated radiomic models may refine the treatment of advanced laryngeal cancers.

Opportunistic viral surveillance confirms the ongoing disease threat grey squirrels pose to sympatric red squirrel populations in the UK.

BACKGROUND: Red Squirrels United was a UK landscape-scale grey squirrel management programme undertaken between 2016 and 2020. METHODS: A total of 11034 grey squirrels were removed by culling, with 1506 necropsied and 1405 suitable for adenovirus (AdV) or squirrelpox virus (SQPV) quantitative PCR (qPCR) analysis. Spleen, lip or hair were extracted, and DNA was isolated, with samples tested in duplicate by qPCR. RESULTS: Of 1378 tissue samples, 43% were positive for AdV and 10% for SQPV. Of 1031 hair samples, 11% were positive for AdV and 10% for SQPV. Overall, 762 of 1405 (54%) animals were positive for one or both viruses. LIMITATIONS: Ad hoc sampling was undertaken from limited geographical areas but provided the only dataset from that period, instead of extrapolating from historical data. CONCLUSIONS: The grey squirrel is an asymptomatic reservoir host for AdV and SQPV. Interspecific infection transmission potential is demonstrated. Grey squirrel management by culling is essential for mainland red squirrel viability until other suitable management tools are available.

Utility and reliability of the Clinical Frailty Scale in patients scheduled for major vascular surgery: a prospective, observational, multicentre observer-blinded study.

BACKGROUND: Frailty is a distinctive health state associated with a loss of physiological reserve that results in higher rates of perioperative complications and impaired return to pre-morbid functional status. It is prevalent in the vascular population; however routine assessment is not common despite national guidance to the contrary. We aimed to evaluate the reliability of the Clinical Frailty Scale in assessing frailty in the surgical vascular population. METHODS: In this prospective, observational, observer-blinded study, we compared assessment of frailty in patients scheduled for major vascular surgery attending the pre-operative assessment clinic using the Clinical Frailty Scale against the Edmonton Frailty Scale. The study investigator completed the Edmonton Frailty Scale assessment; this was compared to the Clinical Frailty Scale assessments performed by the pre-assessment consultant and pre-assessment nurse, who were blinded to the Edmonton Frailty Scale score. The inter-rater reliability of the Clinical Frailty Scale between the pre-assessment consultant and pre-assessment nurse was determined by comparing their frailty scores for each patient. RESULTS: Ninety-seven patients were included in the analysis (median age 72 years, 84% male and 16% female). There was a moderate level of agreement between the Edmonton and Clinical Frailty Scale score for both consultants (87.6% agreement) and pre-assessment nurses (87.6% agreement). There was a substantial level of agreement between consultants and pre-assessment nurses for the Clinical Frailty Scale (89.7% agreement) CONCLUSIONS: The Clinical Frailty Scale is a useful tool to assess frailty in the vascular surgical population. It is more practical than the Edmonton Frailty Scale: quick to complete, requires minimal training and can be used when physical disability is present. TRIAL REGISTRATION: The study was approved by the Wales Health and Care Research Ethics Service (REC reference 17/WA/0160, IRAS 201173). TRIAL REGISTRATION: NCT03403673. Registered 19 January 2018, https://clinicaltrials.gov/ct2/show/NCT03403673.

Risk Management Assessment Improves the Cost-Effectiveness of Invasive Species Prioritisation.

International agreements commit nations to control or eradicate invasive alien species. The scale of this challenge exceeds available resources and so it is essential to prioritise the management of invasive alien species. Species prioritisation for management typically involves a hierarchy of processes that consider the likelihood and scale of impact (risk assessment) and the feasibility, costs and effectiveness of management (risk management). Risk assessment processes are widely used, risk management less so, but are a crucial component of resource decision making. To assess the cost-effectiveness of prioritisation, we considered 26 high-risk species considered for eradication from Great Britain (GB) with pre-existing risk assessment and risk management outputs. We extracted scores to reflect the overall risk to GB posed by the species, together with the estimated cost and the overall feasibility of eradication. We used these to consider the relative reduction in risk per unit cost when managing prioritised species based on different criteria. We showed that the cost-effectiveness of prioritisation within our sample using risk assessment scores alone, performed no better than a random ranking of the species. In contrast, prioritisation including management feasibility produced nearly two orders of magnitude improvement compared to random. We conclude that basing management actions on priorities based solely on risk assessment without considering management feasibility risks the inefficient use of limited resources. In this study, the cost-effectiveness of species prioritisation for action was greatly increased by the inclusion of risk management assessment.

Using structured eradication feasibility assessment to prioritize the management of new and emerging invasive alien species in Europe.

Prioritizing the management of invasive alien species (IAS) is of global importance and within Europe integral to the EU IAS regulation. To prioritize management effectively, the risks posed by IAS need to be assessed, but so too does the feasibility of their management. While the risk of IAS to the EU has been assessed, the feasibility of management has not. We assessed the feasibility of eradicating 60 new (not yet established) and 35 emerging (established with limited distribution) species that pose a threat to the EU, as identified by horizon scanning. The assessment was carried out by 34 experts in invasion management from across Europe, applying the Non-Native Risk Management scheme to defined invasion scenarios and eradication strategies for each species, assessing the feasibility of eradication using seven key risk management criteria. Management priorities were identified by combining scores for risk (derived from horizon scanning) and feasibility of eradication. The results show eradication feasibility score and risk score were not correlated, indicating that risk management criteria evaluate different information than risk assessment. In all, 17 new species were identified as particularly high priorities for eradication should they establish in the future, whereas 14 emerging species were identified as priorities for eradication now. A number of species considered highest priority for eradication were terrestrial vertebrates, a group that has been the focus of a number of eradication attempts in Europe. However, eradication priorities also included a diverse range of other taxa (plants, invertebrates and fish) suggesting there is scope to broaden the taxonomic range of attempted eradication in Europe. We demonstrate that broad scale structured assessments of management feasibility can help prioritize IAS for management. Such frameworks are needed to support evidence-based decision-making.

Prevalence of pelagic dependence among coral reef predators across an atoll seascape.

Coral reef food webs are complex, vary spatially and remain poorly understood. Certain large predators, notably sharks, are subsidized by pelagic production on outer reef slopes, but how widespread this dependence is across all teleost fishery target species and within atolls is unclear. North Malé Atoll (Maldives) includes oceanic barrier as well as lagoonal reefs. Nine fishery target predators constituting ca. 55% of the local fishery target species biomass at assumed trophic levels 3-5 were selected for analysis. Data were derived from carbon (δ13 C), nitrogen (δ15 N) and sulphur (δ34 S) stable isotopes from predator white dorsal muscle samples, and primary consumer species representing production source end-members. Three-source Bayesian stable isotope mixing models showed that uptake of pelagic production extends throughout the atoll, with predatory fishes showing equal planktonic reliance between inner and outer edge reefs. Median plankton contribution was 65%-80% for all groupers and 68%-88% for an emperor, a jack and snappers. Lagoonal and atoll edge predators are equally at risk from anthropogenic and climate-induced changes, which may impact the linkages they construct, highlighting the need for management plans that transcend the boundaries of this threatened ecosystem.

Comparison of the Use of Serum and Plasma as Matrix Specimens in a Widely Used Noncommercial Dengue IgG ELISA.

Although sera are most commonly used in serological diagnostic tests for dengue, sometimes only plasma containing ethylenediaminetetraacetic acid (EDTA) may be available. When we studied the performance of a widely used noncommercial dengue ELISA in the detection of reactive IgG in sera and plasma from the same individuals, we found no significant differences in the diagnostic performance of the assay. The inter-specimen coefficient of variation (CV) of the optical density was 0.081 and the concordance correlation coefficient (CCC) was 0.92, showing a very strong agreement between the two matrix specimens. The intra-specimen CV and CCC were higher for plasma than for serum at low dilutions, but similar at high dilutions. Overall, our results show that the performance of a widely used in-house ELISA using plasma containing EDTA is equivalent to serum with the recommendation to assay the plasma specimens in duplicate to reduce variability of results at lower dilutions.

Novel tri-isotope ellipsoid approach reveals dietary variation in sympatric predators.

Sympatric species may partition resources to reduce competition and facilitate co-existence. While spatial variation and specialization in feeding strategies may be prevalent among large marine predators, studies have focussed on sharks, birds, and marine mammals. We consider for the first time the isotopic niche partitioning of co-occurring, teleost reef predators spanning multiple families. Using a novel tri-isotope ellipsoid approach, we investigate the feeding strategies of seven of these species across an atoll seascape in the Maldives. We demonstrate substantial spatial variation in resource use of all predator populations. Furthermore, within each area, there was evidence of intraspecific variation in feeding behaviors that could not wholly be attributed to individual body size. Assessing species at the population level will mask these intraspecific differences in resource use. Knowledge of resource use is important for predicting how species will respond to environmental change and spatial variation should be considered when investigating trophic diversity.

Estimating contributions of pelagic and benthic pathways to consumer production in coupled marine food webs.

Pelagic and benthic systems usually interact, but their dynamics and production rates differ. Such differences influence the distribution, reproductive cycles, growth rates, stability and productivity of the consumers they support. Consumer preferences for, and dependence on, pelagic or benthic production are governed by the availability of these sources of production and consumer life history, distribution, habitat, behavioural ecology, ontogenetic stage and morphology. Diet studies may demonstrate the extent to which consumers feed on prey in pelagic or benthic environments. But they do not discriminate benthic production directly supported by phytoplankton from benthic production recycled through detrital pathways. The former will track the dynamics of phytoplankton production more closely than the latter. We develop and apply a new analytical method that uses carbon (C) and sulphur (S) natural abundance stable isotope data to assess the relative contribution of pelagic and benthic pathways to fish consumer production. For 13 species of fish that dominate community biomass in the northern North Sea (estimated >90% of total biomass), relative modal use of pelagic pathways ranged from <25% to >85%. Use of both C and S isotopes as opposed to just C reduced uncertainty in relative modal use estimates. Temporal comparisons of relative modal use of pelagic and benthic pathways revealed similar ranking of species dependency over 4 years, but annual variation in relative modal use within species was typically 10%-40%. For the total fish consumer biomass in the study region, the C and S method linked approximately 70% and 30% of biomass to pelagic and benthic pathways, respectively. As well as providing a new method to define consumers' links to pelagic and benthic pathways, our results demonstrate that a substantial proportion of fish biomass, and by inference production, in the northern North Sea is supported by production that has passed through transformations on the seabed.

Mortalities, amyloidosis and other diseases in free-living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands.

Between 2007 and 2014, 337 free-living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands, were examined post mortem as part of a mortality and disease surveillance scheme. Road traffic accidents (RTAs) were attributable for 50.7 per cent (171/337) of the casualties, 34.4 per cent (116/337) succumbed to diseases including fatal exudative dermatitis (FED), 7.1 per cent (24/337) to predation, 6.5 per cent (22/337) to other trauma and 1.2 per cent (4/337) to suspected poisoning. Cat predation accounted for 5 per cent (17/337) of mortalities. Pathologies were diverse and individual animals were often identified with more than one disease process. Squirrelpox virus (SQPV) particles were not detected in selected cases examined by transmission electron microscopy (TEM). Amyloid was identified in 19.3 per cent (65/337) of squirrels, often in conjunction with inflammatory lesions like hepatic capillariasis. A consistent cause of amyloid accumulation was not identified, although there was a significant association of amyloidosis with hepatic capillariasis and FED. In addition to RTAs, amyloidosis and FED have been identified as important causes of squirrel morbidity and mortality on Jersey, while the underlying aetiology and predisposing factors for these two disease complexes are presently unclear. Disease, fragmented woodlands, an increasingly suburban habitat, along with various anthropogenic factors, may jeopardise the long-term viability of this island red squirrel population.

A citizen science based survey method for estimating the density of urban carnivores.

Globally there are many examples of synanthropic carnivores exploiting growth in urbanisation. As carnivores can come into conflict with humans and are potential vectors of zoonotic disease, assessing densities in suburban areas and identifying factors that influence them are necessary to aid management and mitigation. However, fragmented, privately owned land restricts the use of conventional carnivore surveying techniques in these areas, requiring development of novel methods. We present a method that combines questionnaire distribution to residents with field surveys and GIS, to determine relative density of two urban carnivores in England, Great Britain. We determined the density of: red fox (Vulpes vulpes) social groups in 14, approximately 1km2 suburban areas in 8 different towns and cities; and Eurasian badger (Meles meles) social groups in three suburban areas of one city. Average relative fox group density (FGD) was 3.72 km-2, which was double the estimates for cities with resident foxes in the 1980's. Density was comparable to an alternative estimate derived from trapping and GPS-tracking, indicating the validity of the method. However, FGD did not correlate with a national dataset based on fox sightings, indicating unreliability of the national data to determine actual densities or to extrapolate a national population estimate. Using species-specific clustering units that reflect social organisation, the method was additionally applied to suburban badgers to derive relative badger group density (BGD) for one city (Brighton, 2.41 km-2). We demonstrate that citizen science approaches can effectively obtain data to assess suburban carnivore density, however publicly derived national data sets need to be locally validated before extrapolations can be undertaken. The method we present for assessing densities of foxes and badgers in British towns and cities is also adaptable to other urban carnivores elsewhere. However this transferability is contingent on species traits meeting particular criteria, and on resident responsiveness.

The large-scale removal of mammalian invasive alien species in Northern Europe.

Numerous examples exist of successful mammalian invasive alien species (IAS) eradications from small islands (<10 km2 ), but few from more extensive areas. We review 15 large-scale removals (mean area 2627 km2 ) from Northern Europe since 1900, including edible dormouse, muskrat, coypu, Himalayan porcupine, Pallas' and grey squirrels and American mink, each primarily based on daily checking of static traps. Objectives included true eradication or complete removal to a buffer zone, as distinct from other programmes that involved local control to limit damage or spread. Twelve eradication/removal programmes (80%) were successful. Cost increased with and was best predicted by area, while the cost per unit area decreased; the number of individual animals removed did not add significantly to the model. Doubling the area controlled reduced cost per unit area by 10%, but there was no evidence that cost effectiveness had increased through time. Compared with small islands, larger-scale programmes followed similar patterns of effort in relation to area. However, they brought challenges when defining boundaries and consequent uncertainties around costs, the definition of their objectives, confirmation of success and different considerations for managing recolonisation. Novel technologies or increased use of volunteers may reduce costs. Rapid response to new incursions is recommended as best practice rather than large-scale control to reduce the environmental, financial and welfare costs. © 2016 Crown copyright. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Patterns of Coral-Reef Finfish Species Disappearances Inferred from Fishers' Knowledge in Global Epicentre of Marine Shorefish Diversity.

In the Philippines, very high fishing pressure coincides with the globally greatest number of shorefish species, yet no long-term fisheries data are available to explore species-level changes that may have occurred widely in the most species rich and vulnerable marine ecosystem, namely coral reefs. Through 2655 face-to-face interviews conducted between August 2012 and July 2014, we used fishers' recall of past catch rates of reef-associated finfish to infer species disappearances from catches in five marine key biodiversity areas (Lanuza Bay, Danajon Bank, Verde Island Passage, Polillo Islands and Honda Bay). We modeled temporal trends in perceived catch per unit effort (CPUE) based on fishers' reports of typical good days' catches using Generalized Linear Mixed Modelling. Fifty-nine different finfish disappeared from catches between the 1950s and 2014; 42 fish were identified to species level, two to genus, seven to family and eight to local name only. Five species occurring at all sites with the greatest number of fishers reporting zero catches were the green bumphead parrotfish (Bolbometopon muricatum), humphead wrasse (Cheilinus undulatus), African pompano (Alectis ciliaris), giant grouper (Epinephelus lanceolatus) and mangrove red snapper (Lutjanus argentimaculatus). Between the 1950s and 2014, the mean perceived CPUE of bumphead parrotfish declined by 88%, that of humphead wrasse by 82%, African pompano by 66%, giant grouper by 74% and mangrove red snapper by 64%. These declines were mainly associated with excess and uncontrolled fishing, fish life-history traits like maximum body size and socio-economic factors like access to market infrastructure and services, and overpopulation. The fishers' knowledge is indicative of extirpations where evidence for these losses was otherwise lacking. Our models provide information as basis for area-based conservation and regional resource management particularly for the more vulnerable, once common, large, yet wide-ranging reef finfish species.

Evaluation of the flipped classroom approach in a veterinary professional skills course.

BACKGROUND: The flipped classroom is an educational approach that has had much recent coverage in the literature. Relatively few studies, however, use objective assessment of student performance to measure the impact of the flipped classroom on learning. The purpose of this study was to evaluate the use of a flipped classroom approach within a medical education setting to the first two levels of Kirkpatrick and Kirkpatrick's effectiveness of training framework. METHODS: This study examined the use of a flipped classroom approach within a professional skills course offered to postgraduate veterinary students. A questionnaire was administered to two cohorts of students: those who had completed a traditional, lecture-based version of the course (Introduction to Veterinary Medicine [IVM]) and those who had completed a flipped classroom version (Veterinary Professional Foundations I [VPF I]). The academic performance of students within both cohorts was assessed using a set of multiple-choice items (n=24) nested within a written examination. Data obtained from the questionnaire were analyzed using Cronbach's alpha, Kruskal-Wallis tests, and factor analysis. Data obtained from student performance in the written examination were analyzed using the nonparametric Wilcoxon rank sum test. RESULTS: A total of 133 IVM students and 64 VPF I students (n=197) agreed to take part in the study. Overall, study participants favored the flipped classroom approach over the traditional classroom approach. With respect to student academic performance, the traditional classroom students outperformed the flipped classroom students on a series of multiple-choice items (IVM mean =21.4±1.48 standard deviation; VPF I mean =20.25±2.20 standard deviation; Wilcoxon test, w=7,578; P<0.001). CONCLUSION: This study demonstrates that learners seem to prefer a flipped classroom approach. The flipped classroom was rated more positively than the traditional classroom on many different characteristics. This preference, however, did not translate into improved student performance, as assessed by a series of multiple-choice items delivered during a written examination.

Clustering, persistence and control of a pollinator brood disease: epidemiology of American foulbrood.

American foulbrood (AFB), caused by Paenibacillus larvae, is the most damaging bacterial brood disease of the honeybee (Apis mellifera), causing colony deaths on all continents where honeybees are managed. AFB has been a persistent problem in the UK for over 70 years, with a fluctuating number of cases discovered annually. Once diseased colonies are identified, they are destroyed to reduce pathogen spread. We investigated the pattern of AFB cases recorded over the period 1994 to 2012 using spatial-statistical approaches, with a view to identifying the nature of spread across England and Wales. Our results indicated that AFB exhibits significant spatial aggregation at distances from 10 to 30 km, with aggregations lasting between 1 and 5 years. Kernel smoothing indicated areas of elevated relative risk in different years, and these were further detailed by spatial-scan statistics. We identified disease clusters and successfully estimated their size, location and duration. The majority of clusters did not persist in all years, indicating that management measures may lead to localized extinction of the disease. Whilst less common, persistent clusters likely indicate potential endemic or exotic risk points. The application of robust epidemiological approaches to improve the control of AFB is discussed.

Prevalence of Francisella noatunensis subsp. orientalis in cultured tilapia on the island of Oahu, Hawaii.

Francisellosis is an emergent disease in cultured and wild aquatic animals. The causative agent, Francisella noatunensis subsp. orientalis (Fno), is a gram-negative bacterium recognized as one of the most virulent pathogens of warmwater fish. The main objective of this project was to investigate the prevalence of Fno in cultured tilapia (specifically, Mozambique Tilapia Oreochromis mossambicus, Koilapia [also known as Wami Tilapia] O. hornorum, Blue Tilapia O. aureus, and Nile Tilapia O. niloticus hybrids) on the island of Oahu, Hawaii, using conventional and real-time PCR assays followed by statistical modeling to compare the different diagnostic methods and identify potential risk factors. During 2010 and 2012, 827 fish were collected from different geographical locations throughout the island of Oahu. Upon collection of fish, the water temperature in the rearing system and the length of individual fish were measured. Extraction of DNA from different tissues collected aseptically during necropsy served as a template for molecular diagnosis. High correlation between both molecular methods was observed. Moreover, the bacterium was isolated from infected tilapia on selective media and confirmed to be Fno utilizing a species-specific Taqman-based real-time PCR assay. Although a direct comparison of the prevalence of Fno between the different geographical areas was not possible, the results indicate a high prevalence of Fno DNA in cultured tilapia throughout the farm sites located on Oahu. Of the different tilapia species and hybrids currently cultured in Hawaii, Mozambique Tilapia were more susceptible to infection than Koilapia. Water temperature in the rearing systems and fish size also had a strong effect on the predicted level of infection, with fish held at lower temperatures and smaller fish being more susceptible to piscine francisellosis.

PAH contamination in shellfish: modelling to estimate exposure.

Polycyclic aromatic hydrocarbons (PAH) are known carcinogens and are abundant in the environment and foodstuffs. Currently the majority of PAH research focuses on benzo[a]pyrene (BaP), although a much greater range of PAH are known to have detrimental effects to human health. Monitoring a large number of PAH is expensive, time consuming and analytically demanding, yet there is currently no clear basis for determining which PAH should be monitored to give an indication of overall exposure. A thorough statistical examination of the relationships between different PAH in different foodstuffs has not previously been carried out. Using a test dataset of homogenised edible flesh from shellfish samples as a case study a modelling process using principal components analysis regression is proposed to determine which PAH subset (from a total of 27 monitored PAH) should be assessed as indicators for general PAH exposure. Multivariate ordination and clustering show that PAH concentrations of compounds of similar chemical structure can be highly correlated in the samples, e.g. the five ringed isomers PAHs benzo[b]fluoranthene, benzo[j]fluoranthene and benzo[k]fluoranthene. The model selection process determined which subsets of PAH can be used to predict the presence and abundance of other PAHs in shellfish samples. Models were more accurate in predicating PAHs concentrations of PAH where concentrations were measured above the limit of detection (LoD). PAH with values below the LoD were harder to predict accurately. The current analysis highlights that laboratories should focus on the following PAHs BaP, benzo[a]anthracene, benzo[g,h,i]perylene, phenanthrene, benzo[g,h,i]fluoranthene, chrysene, benzo[k]fluoranthene, benzo[b]fluoranthene and fluoranthene when analysing shellfish samples. Focussing monitoring on this group of PAH may give a better indication of overall PAH content of samples that the summed PAH indicator methods currently adopted.