Special Section: Moving Forward in Animal Research Ethics Guest Editorial Reassessing Animal Research Ethics

Animal research has long been a source of biomedical aspirations and moral concern. Examples of both hope and concern are abundant today. In recent months, as is common practice, monkeys have served as test subjects in promising preclinical trials for an Ebola vaccine or treatment 1 , 2 , 3 and in controversial maternal deprivation studies. 4 The unresolved tension between the noble aspirations of animal research and the ethical controversies it often generates motivates the present issue of the Cambridge Quarterly of Healthcare Ethics. As editors of this special section, we hope that these original and timely articles will push the professional discussion of animal research ethics in a positive direction that will benefi t research scientists and others interested in moral problems in animal research. We also look forward to a day when animal research will genuinely meet both appropriate scientifi c and appropriate ethical criteria—criteria that themselves can be improved by critical scrutiny. Animal research—that is, the use of live animals as experimental subjects in biomedical and behavioral fi elds of learning—has been deeply entrenched for well over half a century. One signal development was the enactment in the late 1930s of federal product safety legislation in the United States and other nations that required animal testing of food, drugs, and medical devices prior to use by human subjects or consumers. 5 Another development was the publication of codes of research ethics that called for animal research prior to human research. The Nuremberg Code, published by an American military tribunal in 1947–48 after scrutiny of Nazi medical atrocities, stated that experiments involving the use of human subjects should be " based on the results of animal experimentation. " 6 The Declaration of Helsinki, fi rst published in 1964, reaffi rmed this assumption and added, rather imprecisely, that " the welfare of animals used for research must be respected. " 7 Against the background of such statements, the institutionalization and widespread acceptance of animal research in the twentieth century rested on two basic assumptions, one factual and one moral. The factual assumption was that animal research is suffi ciently reliable as a basis for predicting the effects of drugs, products, and other materials on human beings that animal trials can be expected to yield signifi cant scientifi c conclusions and medical benefi ts to humanity

Bilateral keratoprostheses in a patient with ocular mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) with ocular involvement, also referred to as ocular cicatricial pemphigoid, is a rare, autoimmune blistering disease that can have devastating effects for patients. The resulting corneal neovascularization, recurrent corneal abrasions, and ulceration can ultimately result in severe vision loss. We present a 64-year-old man with recalcitrant ocular MMP and consequently advanced corneal involvement that received bilateral keratoprostheses. This case highlights an aggressive but successful placement of bilateral keratoprostheses in recalcitrant ocular MMP, which restored his vision and ultimately his quality of life

Relieving pain using dose-extending placebos

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated

On the possibility of invertebrate sentience

Mikhalevich & Powell (M&P) set up the basic criteria for according moral status equitably, including the capacity for affect. They argue persuasively against assuming that all invertebrates are insentient and hence ineligible for moral consideration. In addition to the relatively clear case of cephalopods, various arthropods may prove to be sentient. We should be aware of various sources of prejudice that M&P discuss and not assume that it would be absurd to attribute sentience and moral status to certain invertebrates

Stability of the Infant Car Seat Challenge and Risk Factors for Oxygen Desaturation Events

Research suggests that infants with poor neck and upper torso muscle tone experience lateral slouching and a compromised airway when placed in the semi-upright seating position. Studies reveal that 4-60% of premature infants (born at less than 3-7 weeks gestation) may experience oxygen desaturation events when in their child safety seats (CSS), potentially resulting in adverse neurodevelopmental outcomes. Therefore, the American Academy of Pediatrics recommends that premature infants be tested in their CSS prior to hospital discharge. However, neonatal healthcare providers are concerned that this method of testing might not be reliable. No formal studies have investigated the outcomes of repeat testing of premature infants, and little is known about the risk factors for oxygen desaturation events. Therefore, the purpose of this descriptive, non-experimental, observational study was to explore the stability of the one-point Infant Car Seat Challenge (ICSC) and risk factors that may be associated with oxygen desaturation events. A sample of 49 premature infants was used to explore the following variables: 1) pass/fail rates following two (ICSC) observation points, 2) oxygen saturation and desaturation patterns, sleep/wake activity, and a measure of head lag (using the pull-to-sit maneuver) during two ICSCs, and 3) the association between head lag, chronological age, time spent sleeping in the CSS and oxygen desaturation events. Data were analyzed by descriptive and nonparametric statistical tests. This study\u27s findings indicated that 86% of premature infants had stable results, 8% passed rcsc 1 but not ICSC 2, and 6% failed ICSC l and passed ICSC 2. In addition the odds for oxygen desaturation events increased in infants that are born at a gestational age ≤ 34 weeks, were discharged home at a chronological age of \u3e 7 days and had a corrected gestational age of ≤ 37 weeks. Neither head lag or sleep time influenced the ICSC outcomes. Furthermore the ICSC success rate for identifying at risk infants was equal to or better than that of other screening tests for newborn medical conditions. These findings will assist neonatal healthcare providers in making appropriate recommendations for safe travel

Modelling dispersion from elevated sources in a planetary boundary layer dominated by moderate convection

A general method to evaluate dispersion parameters for a turbulent Planetary Boundary Layer (PBL) under convective conditions is described in this paper. The method is based on Taylor’s diffusion theory. By employing the Gaussian plume approach the model performances are evaluated against experimental groundlevel concentrations

A Theory of Bioethics

Intended for students, scholars, and others interested in bioethics, this volume offers a compelling theory of bioethics while eliciting practical implications for issues including medical assistance-in-dying, the right to health care, abortion, animal research, and the definition of death. This title is available as Open Access on Cambridge Core

Comparação entre o modelo CALPUFF e o modelo Lagrangiano LAMBDA com fonte linha

The aim of this study is to compare the CALPUFF and LAMBDA models and evaluate the regulatory model CALPUFF accuracy in situations of line instant source emissions. Line source emissions exist in a variety of situations in the environmental field. Paved and unpaved roads are the most common examples of line sources. For instance, in the mining sector these two types of sources play an important role of anthropogenic influences in the environment. The OLAD experiment is appropriate to evaluate these models and check the accuracy of both. The CALPUFF results show in the simulations for short and long distances a systematic tendency of sub-prediction for the concentration. The LAMBDA model presented better accuracy in the prediction of natural pollutant dispersion even disregarding the spatial variability of meteorological field and topography. When the LAMBDA model is used the flow of pollutants to greater distances is less pronounced, especially because of the time step of one second adopted in the simulation.O objetivo deste estudo é comparar os modelos CALPUFF e LAMBDA e avaliar acurácia do modelo regulatório CALPUFF em situações de emissões de fontes em linha instantâneas. As fontes em linha são muitas vezes utilizadas em simulações de dispersão de poluentes para representar as emissões atmosféricas de vias não pavimentadas e pavimentadas (suspensão de material particulado pela passagem de veículo sobre a via). No setor de mineração estes dois tipos de fontes de emissão constituem uma influência antropogênica importante no ambiente. O experimento OLAD é apropriado para avaliar estes modelos e estabelecer a acurácia de ambos nestas situações descritas. Os resultados do modelo CALPUFF mostrou nas simulações de curtas e longas distâncias uma sistemática tendência de sub previsão das concentrações. O modelo LAMBDA apresentou melhor precisão mesmo desconsiderando a variabilidade espacial do campo meteorológico e da topografia. Quando o modelo LAMBDA é utilizado, o fluxo de poluentes para distâncias maiores é menos pronunciado, especialmente pelo passo de tempo de um segundo adotado na simulação

Two-dimensional dispersion analytical approach: Eddy diffusivities depending on source distance

An analytical air quality dispersion approach based on the steadystate two-dimensional advection-diffusion equation is presented. The solution employs a spectral method and is analytical in the sense that no approximation is made along its derivation. The approach is valid for homogeneous turbulence and for situations of uniform mean wind speed, and for practical purposes, to elevated releases that occur in neutral stability conditions without strong buoyancy. To simulate and compare the results of this approach against observed ground-level crosswind-integrated concentration two eddy diffusivities are considered. The first eddy diffusivity depends on the distance from the source while the second one assumes a constant value independent of the source distance. It is found that the memory effect contained in the eddy diffusivity, which is a function of downwind distance from the source, allows a better description of the turbulent dispersion of atmospheric contaminants released by an elevated continuous point source

Derivation of a decorrelation timescale depending on source distance for inhomogeneous turbulence in a shear dominated planetary boundary layer

In the literature there exists a variety of pollution of dispersion models and in general, Lagrangian stochastic models are efficient and fundamentals tools in the investigation and study of turbulent diffusion phenomenon in the planetary boundary layer. The LAMBDA model is one of them. In this study, the influence of decorrelation time scales in the LAMBDA model under neutral conditions is evaluated. To this end a new parameterization of decorrelation time scales is proposed and validated. This method is based on the Eulerian velocity spectra and a formulation of the evolution of the Lagrangian decorrelation timescales. A spectral distribution of an Eulerian velocity profile and a formulation of the evolution of Lagrangian decorrelation timescales under neutral conditions is used as the forcing mechanisms (shear-dominated boundary layer) for the turbulent dispersion. The model performance was established by comparing the levels of ground-level concentrations of the tracer gas with experimental results from the classical Prarie Grass experiment