Associations between urogenital carcinoma and DECA-BDE (BDE-209) among wild California Sea lions (Zalophus californianus) and Steller Sea lions (Eumetopias jubatus).

Urogenital carcinoma (UGC) is prevalent among California sea lions (Zalophus californianus), while less is known concerning UGC among Steller sea lions (Eumetopias jubatus). Our objective was to investigate associations between UGC and polybrominated diphenyl ethers (PBDEs) among both sea lion species. Twenty-nine California sea lions and 20 Steller sea lions were lethally removed from the Columbia River Basin, Oregon, USA between 2020 and 2021, under Section 120 of the Marine Mammal Protection Act. UGC was diagnosed through gross necropsy and histopathology. Forty PBDE congeners were analyzed in blubber, including BDE-209, a potential carcinogen. Twenty (69 %) California sea lions and one (5 %) Steller sea lion were diagnosed with UGC. All cases were identified as early stage UGC, aside from one California sea lion with more advanced stage UGC. Among California sea lions, associations between PBDEs and UGC were analyzed using logistic regression. In the adjusted model, BDE-209 (log2-transformed) was associated with increased odds of UGC [Odds Ratio (OR): 4.68, 95 % confidence interval: 1.04, 21.0, OR p-value = 0.044). This is the first study to report BDE-209 concentrations in sea lion blubber. The percentages of California and Steller sea lions diagnosed with UGC were higher than expected for wild (non-stranded) sea lions. Our results suggested blubber BDE-209 was potentially associated with UGC in California sea lions in the Columbia River Basin.

EXPLORING THE USE OF THE ERYTHROCYTE SEDIMENTATION RATE AS AN INFLAMMATORY MARKER FOR FREE-RANGING WILDLIFE: A CASE STUDY IN AFRICAN BUFFALO (SYNCERUS CAFFER).

Measuring inflammatory markers is critical to evaluating both recent infection status and overall human and animal health; however, there are relatively few techniques that do not require specialized equipment or personnel for detecting inflammation among wildlife. Such techniques are useful in that they help determine individual and population-level inflammatory status without the infrastructure and reagents that many more-specific assays require. One such technique, known as the erythrocyte sedimentation rate (ESR), is a measure of how quickly erythrocytes (red blood cells) settle in serum, with a faster rate indicating a general, underlying inflammatory process is occurring. The technique is simple, inexpensive, and can be performed in the field without specialized equipment. We took advantage of a population of African buffalo (Syncerus caffer), well studied from June 2014 to May 2017, to understand the utility of ESR in an important wildlife species. When ESR was compared with other markers of immunity in African buffalo, it correlated to known measures of inflammation. We found that a faster ESR was significantly positively correlated with increased total globulin levels and significantly negatively correlated with increased red blood cell count and albumin levels. We then evaluated if ESR correlated to the incidence of five respiratory pathogens and infection with two tick-borne pathogens in African buffalo. Our results suggest that elevated ESR is associated with the incidence of bovine viral diarrhea virus infection, parainfluenza virus, and Mannheimia haemolytica infections as well as concurrent Anaplasma marginale and Anaplasma centrale coinfection. These findings suggest that ESR is a useful field test as an inflammatory marker in individuals and herds, helping us better monitor overall health status in wild populations.

Clinical utility of abdominal multidetector CT in 85 goats with suspected abdominal disease.

Diagnosing the cause of abdominal disease in goats can be challenging. Clinical history, physical investigation, and laboratory findings do not always allow definitive identification of intra-abdominal disease or the underlying cause. Multidetector CT (MDCT) has become more readily available and now often replaces or augments other abdominal imaging techniques. The objective of this retrospective, observational, descriptive study was to investigate the clinical utility of MDCT for evaluation of the abdomen in goats with suspected abdominal disease involving the urinary, gastrointestinal, reproductive tracts and abdominal wall. Medical records (1/2009-12/2017) were reviewed for all goats undergoing an abdominal MDCT. Signalment, clinical history, examination and MDCT findings and outcome were recorded and categorized by abdominal organ system and wall lesion. Clinical problems and MDCT findings were compared in the various abdominal categories. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (OR) were calculated for MDCT, using clinical examination findings as the reference standard. A total of 85 goats underwent an abdominal MDCT examination. The sensitivity of MDCT for detecting urinary, gastrointestinal, reproductive tract, and abdominal wall abnormalities in goats with clinical problems related to these body systems was high at 94.7 %, 78.3%, 94.1%, and 100%, and the specificity was high at 95.6%, 96.7%, 93.9%, and 100%, respectively. The PPV was 94.7%, 90.0 %, 80.0%, and 100.0%, the NPV was 95.6%, 92.1%, 98.4%, and 100%, and the OR were 387.0, 104.4, 248.0, and infinite. In conclusion, findings supported the use of MDCT as an adjunct diagnostic test for assessing goats with abdominal disease.

Automation of hybridization and capture based next generation sequencing library preparation requires reduction of on-deck bead binding and heated wash temperatures.

Capture-based library preparation for next generation sequencing (NGS) offers a balance between sequencing depth and bioinformatics cost of analysis. Liquid handling automation enhances the reliability of the library preparation process by reducing sample-to-sample variation and substantially enhances throughput, particularly when it can be employed in a 'walk-away' fashion with limited hands-on interaction. This requires complex series of mixing and heating steps like those utilized in capture chemistries to happen on the liquid handler. While developing liquid handling automation for Integrated DNA Technologies (IDT) xGen Exome, Illumina TruSight Oncology 500, and Personal Genome Diagnostics (PGDx) elio Plasma Resolve chemistries on the PerkinElmer Sciclone liquid handler, we found that applying the capture temperatures recommended for manual library preparation results in low yield on automation. To restore the final library yield, we reduced bead binding and/or heated wash temperatures of the Peltier heaters on the liquid handlers by about 10°C. Since this applied across three unique capture-based chemistries, we consider this a generalizable principle of automating capture on the Sciclone. We hypothesize that this is driven by the very different thermodynamic environments represented by a sealed plate on a thermal cycler and a plate with a lid on a Peltier heater. This phenomenon should be considered when automating NGS library preparation on PerkinElmer Sciclone instruments.

Required parameters for modelling heterogeneous geographically dispersed manufacturing systems.

COVID-19 and global crises/events are driving governments to rethink their national manufacturing strategies. The drastic change of societal conditions has exposed our reliance on a constrained set of production practices. Furthermore, the future manufacturing landscape indicates - supply chain crises, trade agreements and natural disasters - a high level of volatility which requires a response that is far from being achieved. While these emergent challenges have called the efficacy of established practices into question, new manufacturing technologies, such as Additive Manufacturing (AM), present the capability to provide a solution. One proposal is agent-based brokering of AM which could be a method for tackling local, regional, national, and international production needs. However, to achieve the reality of brokered AM, it is imperative that the diversity of AM capability is considered. Diversity that existing homogeneous modelling of AM and manufacturing systems rarely consider or capture. This paper conceptualizes the reality of AM systems and elucidates parameters that are necessary for successful modelling and subsequent co-ordination. Having presented the required parameters the paper continues to discuss requisite levels of abstraction, suitable performance metrics and the role of humans in agent-based manufacturing systems.

Sablefish (Anoplopoma fimbra Pallas, 1814) plasma biochemistry and hematology reference intervals including blood cell morphology.

Plasma biochemistry and hematology reference intervals are integral health assessment tools in all medical fields, including aquatic animal health. As sablefish (Anoplopoma fimbria) are becoming aquaculturally and economically more important, this manuscript provides essential reference intervals (RI) for their plasma biochemistry and hematology along with reference photomicrographs of blood cells in healthy, fasted sablefish. Blood cell morphology can differ between fish species. In addition, blood cell counts and blood chemistry can vary between fish species, demographics, water conditions, seasons, diets, and culture systems, which precludes the use of RI's from other fish species. For this study, blood was collected for plasma biochemistry and hematology analysis between June 20 and July 18, 2019, from healthy, yearling sablefish, hatched and reared in captivity on a commercial diet. Overnight fast of 16-18 hours did not sufficiently reduce lipids in the blood, which led to visible lipemia and frequent rupture of blood cells during analysis. Therefore, sablefish should be fasted for 24 to 36 hours before blood is collected to reduce hematology artifacts or possible reagent interference in plasma biochemistry analysis. Lymphocytes were the most dominant leukocytes (98%), while eosinophils were rare, and basophils were not detected in sablefish. Neutrophils were very large cells with Döhle bodies. In mammals and avian species, Döhle bodies are usually signs of toxic change from inflammation, but no such association was found in these fish. In conclusion, lipemia can interfere with sablefish blood analysis, and available removal methods should be evaluated as fasting for up to 36 h might not always be feasible. Also, more studies are required to establish RI for different developmental stages and rearing conditions.

A case of canine renal lymphoma of granular lymphocytes with severe polycythemia.

BACKGROUND: Renal lymphoma in dogs is rare and has a poor prognosis. Granular lymphocyte morphology is rarely reported in canine renal lymphoma. Mild to moderate polycythemia is reported in a number of canine renal lymphoma cases. CASE PRESENTATION: A 10-year-old Labrador retriever presented to a university veterinary teaching hospital after a 1-month history of polyuria, polydipsia, and pollakiuria and a 2-week history of abdominal distention, lethargy, and increased respiratory effort. Abdominal ultrasound showed a wedge-shaped to rounded, heterogeneously hypoechoic mass lesion in the left kidney. Cytologic analysis of a percutaneous aspirate of the mass was consistent with lymphoma of granular lymphocytes. Severe polycythemia (hematocrit 0.871) was noted on a complete blood cell count. Clonality analysis identified a clonally rearranged T-cell receptor (TCR) gene and immunohistochemical staining was CD3+, CD79a- and CD11d+, supporting cytotoxic T-cell lymphoma. CONCLUSIONS: To our knowledge, this is the first report of renal cytotoxic T-cell lymphoma with severe polycythemia in a dog. Severe polycythemia and renal cytotoxic T-cell lymphoma are both rare in dogs; this report adds to the body of knowledge on these conditions.

Survey of Institutional Teaching Approaches to Clinical-Year Clinical Pathology Instruction and Comparison with Prior Survey Results.

Teaching approaches to veterinary clinical pathology in the final (clinical) year of veterinary school are often different than those for other specialties. Anecdotally, many schools teach these rotations separately from the routine diagnostic service, but minimal published data are available on this topic or on approaches to teaching and assessment in these rotations. An online survey of 69 veterinary institutions around the world was conducted in 2019. A total of 30 completed surveys were received from 10 countries; 22 completed responses were from North American institutions (73.3%). Survey question categories included information on basic rotations, including microscopy format, personnel involved in instruction, and assessment methods; information on advanced rotations; and challenges and successes with clinical pathology instruction. Data were analyzed and, when appropriate, compared with results from a similar survey conducted in 1997. Formats and content varied greatly among institutions. Several shifts in teaching strategies and rotation format over time were found since the 1997 survey, including increased use of projection microscopy and decreased use of multiheaded microscopy in 2019. More teaching by medical technologists and residents, less teaching by faculty, and a significant increase in the number of students per rotation were seen in 2019 compared with 1997. Several free-text comments referred to challenges related to increasing class size. These data and the comparison with the prior survey highlight common challenges and potential solutions to final-year clinical pathology instruction. Creation of specific, measurable objectives for clinical pathology competence may aid future development and refinement of clinical pathology teaching.

Hematology and Culture Assessment of Cranially Implanted Rhesus Macaques (Macaca mulatta).

The use of percutaneous cranial implants in rhesus macaques (Macaca mulatta) has long been a valuable tool for neuroscience research. However, when treating and assessing these animals, veterinarians are required to make assumptions about diagnostic results due to a lack of research into how these implants affect physiology. Microbial cultures of cranial implant sites show an abundance of colonizing bacteria, but whether these microbes affect animal health and wellbeing is poorly understood. In addition, microbial antibiotic resistance can present significant health concerns for both the animals and the researchers. To help elucidate the relationship between percutaneous cranial implants and blood parameters, complete blood cell counts and serum chemistry results were assessed on 57 nonhuman primates at our institution from September 2001 to March 2017. Generalized estimating equations were used to compare the results before and after an animal's first implant surgery. This modelling showed that cranial implants were a significant predictor of alterations in the number of neutrophils, lymphocytes, and red blood cells, and in the concentration of hemoglobin, alkaline phosphatase, creatinine, calcium, phos- phorus, total protein, albumin, and globulin. Anaerobic and aerobic bacterial cultures were performed to identify bacteria associated with cranial implants. Staphylococcus spp., Streptococcus spp., and Corynebacterium spp. comprised the majority of the aerobic bacterial isolates, while Fusobacterium spp., Peptostreptococcus spp. and Bacterioides fragilis comprised the majority of anaerobic bacterial isolates. Using a Pearson r correlation for statistical analysis, we assessed whether any of these bacterial isolates developed antibiotic resistances over time. Cefazolin, the most frequently used antibiotic in monkeys in this study, was the only antimicrobial out of 41 agents tested to which bacteria developed resistance over time. These results indicate that percutaneous implants are associated with a generalized inflammatory state, multiple bacterial species are present at the implant site, and these bacteria may contribute to the inflammatory response.

Hematologic Conditions of Small Ruminants.

Anemia is a clinically important syndrome in small ruminants. Anemia can be divided into regenerative and nonregenerative forms. Differentials for regenerative anemia include hemorrhage owing to gastrointestinal or external parasitism or hemostatic disorders, and hemolysis owing to infectious, osmotic, toxic, and nutritional causes. Differentials for nonregenerative anemia include inflammatory and chronic diseases, renal failure, pancytopenia, copper deficiency, and heavy metal toxicosis. Iron deficiency anemia can be caused by chronic gastrointestinal and external hemorrhage or nutritional deficiency and may be mildly regenerative or nonregenerative. Appropriate diagnostic tests are described along with treatments, including blood transfusion, parasite control, and prevention.

Historicizing Modern Slavery: Free-Grown Sugar as an Ethics-Driven Market Category in Nineteenth-Century Britain.

The modern slavery literature engages with history in an extremely limited fashion. Our paper demonstrates to the utility of historical research to modern slavery researchers by explaining the rise and fall of the ethics-driven market category of "free-grown sugar" in nineteenth-century Britain. In the first decades of the century, the market category of "free-grown sugar" enabled consumers who were opposed to slavery to pay a premium for a more ethical product. After circa 1840, this market category disappeared, even though considerable quantities of slave-grown sugar continued to arrive into the UK. We explain the disappearance of the market category. Our paper contributes to the on-going debates about slavery in management by historicizing and thus problematizing the concept of "slavery". The paper challenges those modern slavery scholars who argue that lack of consumer knowledge about product provenance is the main barrier to the elimination of slavery from today's international supply chains. The historical research presented in this paper suggests that consumer indifference, rather than simply ignorance, may be the more fundamental problem. The paper challenges the optimistic historical metanarrative that pervades much of the research on ethical consumption. It highlights the fragility of ethics-driven market categories, offering lessons for researchers and practitioners seeking to tackle modern slavery.

Influence of specific management practices on blood selenium, vitamin E, and beta-carotene concentrations in horses and risk of nutritional deficiency.

BACKGROUND: Selenium or alpha-tocopherol deficiency can cause neuromuscular disease. Beta-carotene has limited documentation in horses. OBJECTIVE: To evaluate the effect of owner practices on plasma beta-carotene concentration and risk of selenium and alpha-tocopherol deficiencies. ANIMALS: Three-hundred and forty-nine adult (≥1 year), university and privately owned horses and mules. METHODS: Cross-sectional study. Whole blood selenium, plasma alpha-tocopherol, and plasma beta-carotene concentrations were measured once. Estimates of daily selenium and vitamin E intake, pasture access, and exercise load were determined by owner questionnaire. Data were analyzed using t tests, Mann-Whitney tests, parametric or nonparametric analysis of variance (ANOVA), Kruskal-Wallis test, Spearman's correlation and contingency tables (P < .05). RESULTS: Nearly 88% of the horses received supplemental selenium; 71.3% received ≥1 mg/d. Low blood selenium concentration (<80 ng/mL) was identified in 3.3% of horses, and 13.6% had marginal concentrations (80-159 ng/mL). Non-supplemented horses were much more likely to have low blood selenium (odds ratio [OR], 20.2; 95% confidence interval [CI], 9.26-42.7; P < .001). Supplemental vitamin E was provided to 87.3% of horses; 57.7% received ≥500 IU/d. Deficient (<1.5 µg/mL) and marginal (1.5-2.0 µg/mL) plasma (alpha-tocopherol) occurred in 15.4% and 19.9% of horses, respectively. Pasture access (>6 h/d) and daily provision of ≥500 IU of vitamin E was associated (P < .001) with higher plasma alpha-tocopherol concentrations. Plasma beta-carotene concentration was higher in horses with pasture access (0.26 ± 0.43 versus 0.12 ± 0.13 µg/mL, P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Suboptimal blood selenium and plasma alpha-tocopherol concentrations occurred in 16.7% and 35.5% of horses, respectively, despite most owners providing supplementation. Inadequate pasture access was associated with alpha-tocopherol deficiency, and reliance on selenium-containing salt blocks was associated with selenium deficiency.

Comparison of serum cytokine concentrations between healthy dogs and canine osteosarcoma patients at the time of diagnosis.

Systemic immune responses in cancer patients are of tremendous importance, both to advance understanding of disease mechanisms and for development of new diagnostic testing. Minimal published information is available on the systemic cytokine response in canine osteosarcoma (OS) patients. The goal of this study was to investigate serum cytokine alterations present in OS patients at the time of diagnosis. Serum samples from 22 canine OS patients at the time of diagnosis and 18 healthy control dogs were evaluated via multiplex immunoassay for 14 analytes. Significant increases in serum interleukin-8 (IL-8) and interleukin-12p40 (IL-12p40) concentrations were found in OS patients when compared to healthy controls. The results correlate with several published studies on serum cytokine alterations in human OS patients. These data add to the growing body of knowledge on immunologic alterations in OS, including potential immunomodulatory therapy of canine patients, and support future studies on serum cytokine testing to investigate diagnostic and prognostic utility.

Good at heart: Developing a tertiary perinatal cardiac service; the first eight years of experience.

BACKGROUND: Maternal cardiac disease is the most common cause of indirect maternal death, and women with pre-existing cardiac disease have complex medical, obstetric and anaesthetic requirements. Our hospital commenced a multidisciplinary perinatal cardiac service in 2009 to optimise outcomes in women with cardiac disease. AIM: To assess the maternal and perinatal outcomes of women referred to the clinic to evaluate clinical practice and inform future service provision. MATERIALS AND METHODS: This is a single-centre retrospective study of women referred to the perinatal cardiac service between 2009-2016. Data collected included: demographic details; cardiac diagnosis; pregnancy outcomes, including anaesthetic and delivery complications, and admission to intensive care unit (ICU)/high dependency unit (HDU). RESULTS: One hundred and fifty-two women were referred for care in 165 pregnancies. Congenital heart disease was the most common indication for referral (35%), followed by maternal cardiac arrhythmia (26%) and valvular disease (18%). The perinatal mortality rate was 2%, median gestational age at delivery was 38 weeks 4 days, fetal growth restriction (customised birthweight <10th centile) was 9% although 25 (17%) pregnancies resulted in preterm birth, 36% of which were spontaneous and 64% were iatrogenic. Maternal outcomes were favourable and there were no maternal deaths. However, 51% of women required a caesarean section, and 23% who achieved a live birth required ICU/HDU admission. CONCLUSION: This study confirmed that women with cardiac disease are at increased risk of preterm birth, and high acuity in the peripartum period but otherwise good maternal and perinatal outcomes. An integrated multidisciplinary perinatal cardiac service can optimise perinatal outcomes in these women.

Allenoate Prenucleophiles: A Triply Diastereoselective Approach to ß-Hydroxy Esters Containing All-Carbon α-Quaternary Centers.

Allenyl esters activated by titanium(IV) underwent additions to a wide range of aldehydes in high regio- and diastereoselectivities leading to products containing an all-carbon quaternary center bearing an α-vinyl group that was installed with high selectivity for the Z-geometry. An aldol product was also converted to an indanone offering a new route to this important compound class. Product triple diastereoselectivity has been rationalized using a concerted transition-state model.

Mitral Valve Prolapse and Sudden Cardiac Death: A Systematic Review.

Background The relationship between mitral valve prolapse ( MVP ) and sudden cardiac death ( SCD ) remains controversial. In this systematic review, we evaluate the relationship between isolated MVP and SCD to better define a potential high-risk subtype. In addition, we determine whether premortem parameters could predict SCD in patients with MVP and the incidence of SCD in MVP . Methods and Results Electronic searches were conducted in PubMed and Embase for all English literature articles published between 1960 and 2018 regarding MVP and SCD or cardiac arrest. We also identified articles investigating predictors of ventricular arrhythmias or SCD and cohort studies reporting SCD outcomes in MVP . From 2180 citations, there were 79 articles describing 161 cases of MVP with SCD or cardiac arrest. The median age was 30 years and 69% of cases were female. Cardiac arrest occurred during situations of stress in 47% and was caused by ventricular fibrillation in 81%. Premature ventricular complexes on Holter monitoring (92%) were common. Most cases had bileaflet involvement (70%) with redundancy (99%) and nonsevere mitral regurgitation (83%). From 22 articles describing predictors for ventricular arrhythmias or SCD in MVP , leaflet redundancy was the only independent predictor of SCD . The incidence of SCD with MVP was estimated at 217 events per 100 000 person-years. Conclusions Isolated MVP and SCD predominantly affects young females with redundant bileaflet prolapse, with cardiac arrest usually occurring as a result of ventricular arrhythmias. To better understand the complex relationship between MVP and SCD , standardized reporting of clinical, electrophysiological, and cardiac imaging parameters with longitudinal follow-up is required.

Achieving "Zero" Defects for Visible Particles in Injectables.

The reduction of visible particles in injectable products is an important element in the consistent delivery of high-quality parenteral products. An important part of this effort is the control of particles that may emanate from the primary packaging materials. The Parenteral Drug Association (PDA), with the support of the Pharmaceutical Manufacturers Forum (PMF), has undertaken the task of developing test methods to assess the cleanliness of primary packaging components used in the manufacturing of sterile injectable products. Further work is focused on end-to-end analysis of the supply chain to identify additional points where particles may enter the finished product workflow. This includes shipment, receipt, transfer, and fill and finishing operations. This information and appropriate corrective actions and control methods, coupled with appropriate patient risk-based acceptance limits, are intended to provide better and more consistent supply of injectable products that meet current compendial and good manufacturing practice (GMP) expectations. Aligning control limits between supplier and pharmaceutical manufacturers will offer further improvement. This paper describes the formation of a task force to address these needs and current progress to date.LAY ABSTRACT: Visible particles must be controlled in parenteral products. Such particles come from many sources including the primary packaging materials. The Parenteral Drug Association (PDA), with the support of the Pharmaceutical Manufacturers Forum (PMF), has formed a task force to review and improve particle measurement methods and perform an end-to-end analysis of how particles may enter into parenteral products. These activities are intended to lead to more consistent control limits for visible particles and ultimately more consistent supply of high quality injectable products.