A Zoopolean look at animal research ethics

I will discuss how animal laboratory research can be ethically analyzed using Donaldson and Kymlicka’s political theory of animal rights. To accomplish this, I will not presuppose their strong animal rights framework. Donaldson and Kymlicka’s approach revolves around some basic human-animal relationships, reflecting the relational turn in applied ethics writ large. However, they do not discuss laboratory animal research in any detail, and so an extension to that domain of animal use is in order. Donaldson and Kymlicka’s emphasis on human-animal relationships is useful for reminding ourselves that in laboratories various staff or personnel can develop bonds with captive animals that make it difficult to follow certain protocols as well as create a deep and lasting negative impression. Though, when suitably modified, Donaldson and Kymlicka’s political theory can apply to animal research ethics, it can only do so though if we ask more from all members of our society

Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis.</p> <p>The objectives of this study were to determine whether 1) low urine pH, or 2) acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a) fragility fractures; and b) five-year change of bone mineral density (BMD) in adults.</p> <p>Methods</p> <p>Design: Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion) in fasting morning with the incidence of fractures (6804 person years). Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651). Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index.</p> <p>Results</p> <p>There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders.</p> <p>Conclusion</p> <p>Urine pH and urine acid excretion do not predict osteoporosis risk.</p

The Significance of African Lions for the Financial Viability of Trophy Hunting and the Maintenance of Wild Land

Recent studies indicate that trophy hunting is impacting negatively on some lion populations, notably in Tanzania. In 2004 there was a proposal to list lions on CITES Appendix I and in 2011 animal-welfare groups petitioned the United States government to list lions as endangered under their Endangered Species Act. Such listings would likely curtail the trophy hunting of lions by limiting the import of lion trophies. Concurrent efforts are underway to encourage the European Union to ban lion trophy imports. We assessed the significance of lions to the financial viability of trophy hunting across five countries to help determine the financial impact and advisability of the proposed trade restrictions. Lion hunts attract the highest mean prices (US$24,000–US$71,000) of all trophy species. Lions generate 5–17% of gross trophy hunting income on national levels, the proportional significance highest in Mozambique, Tanzania, and Zambia. If lion hunting was effectively precluded, trophy hunting could potentially become financially unviable across at least 59,538 km2 that could result in a concomitant loss of habitat. However, the loss of lion hunting could have other potentially broader negative impacts including reduction of competitiveness of wildlife-based land uses relative to ecologically unfavourable alternatives. Restrictions on lion hunting may also reduce tolerance for the species among communities where local people benefit from trophy hunting, and may reduce funds available for anti-poaching. If lion off-takes were reduced to recommended maximums (0.5/1000 km2), the loss of viability and reduction in profitability would be much lower than if lion hunting was stopped altogether (7,005 km2). We recommend that interventions focus on reducing off-takes to sustainable levels, implementing age-based regulations and improving governance of trophy hunting. Such measures could ensure sustainability, while retaining incentives for the conservation of lions and their habitat from hunting

Factors associated with preservation of facial nerve function after surgical resection of vestibular schwannoma

Avoidance of facial nerve palsy is one of the major goals of vestibular schwannoma (VS) microsurgery. In this study, we examined the significance of previously implicated prognostic factors (age, tumor size, the extent of resection and the surgical approach) on post-operative facial nerve function. We selected all VS patients from prospectively collected database (1984–2009) who underwent microsurgical resection as their initial treatment for histopathologically confirmed VS. The effect of variables such as surgical approach, tumor size, patient age and extent of resection on rates facial nerve dysfunction after surgery, were analyzed using multivariate logistic regression. Patients with preoperative facial nerve dysfunction (House-Brackman [HB] score 3 or higher) were excluded, and HB grade of 1 or 2 at the last follow-up visit was defined as “facial nerve preservation.” A total of 624 VS patients were included in this study. Multivariate logistic regression analysis found that only pre-operative tumor size significantly predicted poorer facial nerve outcome for patients followed-up for ≥6 and ≥12 months (OR 1.27, 95% CI 1.09–1.49, p < 0.01; OR 1.35, 95% CI 1.10–1.67, P < 0.01, respectively). We found no significant relationship between facial nerve function and age, extent of resection, surgical approach, or tumor size (when extent of resection and surgical approach were included in the regression analysis). Because facial nerve palsy is a debilitating and psychologically devastating condition for the patient, we suggest altering surgical aggressiveness in patients with unfavorable tumor anatomy, particularly in cases with large tumors where overaggressive resection might subject the patient to unwarranted risk. Residual disease can be followed and controlled with radiosurgery if interval growth is noted

Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

<p>Abstract</p> <p>Background</p> <p>The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.</p> <p>Methods</p> <p>Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement.</p> <p>Results</p> <p>Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement.</p> <p>Conclusion</p> <p>All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.</p

Fussy Feeders: Phyllosoma Larvae of the Western Rocklobster (Panulirus cygnus) Demonstrate Prey Preference

The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P. cygnus were previously unknown, hampering both management and aquaculture efforts for this species. Ship-board feeding trials of wild-caught mid-late stage P. cygnus phyllosoma in the eastern Indian Ocean, off the coast of Western Australia, were conducted in July 2010 and August-September 2011. In a series of experiments, phyllosoma were fed single and mixed species diets of relatively abundant potential prey items (chaetognaths, salps, and krill). Chaetognaths were consumed in 2–8 times higher numbers than the other prey, and the rate of consumption of chaetognaths increased with increasing concentration of prey. The highly variable lipid content of the phyllosoma, and the fatty acid profiles of the phyllosoma and chaetognaths, indicated they were from an oligotrophic oceanic food chain where food resources for macrozooplankton were likely to be constrained. Phyllosoma fed chaetognaths over 6 days showed significant changes in some fatty acids and tended to accumulate lipid, indicating an improvement in overall nutritional condition. The discovery of a preferred prey for P. cygnus will provide a basis for future oceanographic, management and aquaculture research for this economically and ecologically valuable species

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

True versus False Parasite Interactions: A Robust Method to Take Risk Factors into Account and Its Application to Feline Viruses

International audienceBACKGROUND: Multiple infections are common in natural host populations and interspecific parasite interactions are therefore likely within a host individual. As they may seriously impact the circulation of certain parasites and the emergence and management of infectious diseases, their study is essential. In the field, detecting parasite interactions is rendered difficult by the fact that a large number of co-infected individuals may also be observed when two parasites share common risk factors. To correct for these "false interactions", methods accounting for parasite risk factors must be used. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper we propose such a method for presence-absence data (i.e., serology). Our method enables the calculation of the expected frequencies of single and double infected individuals under the independence hypothesis, before comparing them to the observed ones using the chi-square statistic. The method is termed "the corrected chi-square." Its robustness was compared to a pre-existing method based on logistic regression and the corrected chi-square proved to be much more robust for small sample sizes. Since the logistic regression approach is easier to implement, we propose as a rule of thumb to use the latter when the ratio between the sample size and the number of parameters is above ten. Applied to serological data for four viruses infecting cats, the approach revealed pairwise interactions between the Feline Herpesvirus, Parvovirus and Calicivirus, whereas the infection by FIV, the feline equivalent of HIV, did not modify the risk of infection by any of these viruses. CONCLUSIONS/SIGNIFICANCE: This work therefore points out possible interactions that can be further investigated in experimental conditions and, by providing a user-friendly R program and a tutorial example, offers new opportunities for animal and human epidemiologists to detect interactions of interest in the field, a crucial step in the challenge of multiple infections

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy