Hematological, biochemical, and morphological parameters as prognostic indicators for stranded common dolphins (Delphinus delphis) from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 30 (2014): 864–887, doi:10.1111/mms.12093.The current paucity of published blood values and other clinically relevant data for short-beaked common dolphins, Delphinus delphis, hinders the ability of veterinarians and responders to make well-informed diagnoses and disposition decisions regarding live strandings of this species. This study examined hematologic, clinical chemistry, and physical parameters from 26 stranded common dolphins on Cape Cod, Massachusetts, in light of their postrelease survival data to evaluate each parameter's efficacy as a prognostic indicator. Statistically and clinically significant differences were found between failed and survived dolphins, including lower hematocrit, hemoglobin, TCO2, and bicarbonate and higher blood urea nitrogen, uric acid, and length-to-girth ratios in animals that failed. In general when compared to survivors, failed dolphins exhibited acidosis, dehydration, lower PCVs, and decreased body condition. Additionally, failed dolphins had the highest ALT, AST, CK, LDH, GGT, and lactate values. These blood values combined with necropsy findings indicate that there are likely a variety of factors affecting postrelease survival, including both preexisting illness and stranding-induced conditions such as capture myopathy. Closer evaluation of these parameters for stranded common dolphins on point of care analyzers in the field may allow stranding personnel to make better disposition decisions in the future.The John H. Prescott Marine Mammal Rescue Assistance Program provided support for stranding response efforts during this study period (Grants: NA11NMF4390078, NA11NMF4390079, NA11NMF4390093). We would like to thank the Pegasus Foundation and Barbara Birdsey for their support and funding for the IFAW Satellite Tag Program. This project would not have been possible without a summer research grant from the US Army Medical Research and Material Command through Tufts Cummings School of Veterinary Medicine (TCSVM)

A comparison of postrelease survival parameters between single and mass stranded delphinids from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 32 (2016): 161–180, doi:10.1111/mms.12255.The viability of healthy single stranded dolphins as immediate release candidates has received little attention. Responders have been reluctant to release lone delphinids due to their social needs, even when they pass the same health evaluations as mass stranded animals. This study tracked postrelease success of 34 relocated and released satellite tagged delphinids from single and mass strandings. Three postrelease survival parameters (transmission duration, swim speed, and daily distance) were examined to evaluate whether they differed among single stranded/single released (SS/SR), mass stranded/single released (MS/SR), or mass stranded/mass released (MS/MR) dolphin groups. Comparisons were also made between healthy and borderline release candidates. Satellite tags transmitted for a mean of 21.2 d (SD = 19.2, range = 1–79), daily distance traveled was 42.0 km/d (11.25, 20.96–70.72), and swim speed was 4.3 km/h (1.1, 2.15–8.54). Postrelease parameters did not differ between health status groups, however, SS/SR dolphins transmitted for a shorter mean duration than MS/MR and MS/SR groups. Postrelease vessel-based surveys confirmed conspecific group location for two healthy, MS/SR dolphins. Overall, these results support the potential to release healthy stranded single delphinids; however, further refinement of health assessment protocols for these challenging cases is needed.National Oceanic and Atmospheric Administration's National Marine Fisheries Service (NOAA NMFS); John H. Prescott Marine Mammal Rescue Assistance Program Grant Numbers: NA11NMF4390078, NA11NMF4390079, NA11NMF439009

White matter damage and cognitive impairment after traumatic brain injury

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute / chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions

Bubbles in live-stranded dolphins

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Proceedings of the Royal Society B : Biological Sciences 279 (2012): 1396-1404, doi:10.1098/rspb.2011.1754.Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber–muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.Funding for this work was provided by the US Office of Naval Research Award no. N000140811220 and the International Fund for Animal Welfare

Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells.

Huntington's disease is a neurodegenerative disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types. Here, we show that caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3 cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to cleavable htt, caspase-resistant htt with an expanded polyglutamine tract has reduced toxicity in apoptotically stressed neuronal and nonneuronal cells and forms aggregates at a much reduced frequency. These results suggest that inhibiting caspase cleavage of htt may therefore be of potential therapeutic benefit in Huntington's disease

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

Rapid detection of heart failure using a spectroscopic liquid biopsy

Heart disease is growing annually across the globe with numbers expected to rise to 46% of the population by 2030. Early detection is vital for several reasons, firstly it improves the long-term prognosis of the patient by admitting them through the appropriate pathway faster, secondly it reduces healthcare costs by streamlining diagnosis and finally, in combination with management or treatment, it can prevent the progression of the disease which in turn improves the patient’s quality of life. Therefore, there lies an increasing need to develop assays which can rapidly detect heart disease at an early stage. The Dxcover® liquid biopsy platform employs infrared spectroscopy and artificial intelligence, to quickly analyse minute amounts of patient serum. In this study, discrimination between healthy controls and diseased patients was obtained with an area under the receiver operating characteristic curve (AUC) of 0.89. When assessing the heart failure vs all patients, which is most akin to what would be observed in a triage setting, the model when tuned to a minimum of 45% specificity yielded a sensitivity of 89% and an NPV of 0.996, conversely when sensitivity was set at a 45% minimum, the specificity was 96%, giving an NPV of 0.991 when using a 1.5% prevalence. Other models were assessed in parallel, but the performance of the ORFPLS model was overall superior to the other models tested. In this large scale (n = 404) proof-of-concept study, we have shown that the Dxcover liquid biopsy platform has the potential to be a viable triage tool in emergency and routine situations for the diagnosis of heart failure

Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.The SE3238 project “Meta-analysis of diagnostic tests and modelling to identify appropriate testing strategies to reduce M. bovis infection in GB herds” was funded by the UK Department for Environment, Food and Rural Affairs (Defra).http://www.elsevier.com/locate/prevetmedam2018Veterinary Tropical Disease