Observational Study Design in Veterinary Pathology, Part 1: Study Design

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods

The Galactic Distribution of OH/IR Stars

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Buying Years to Extinction: Is Compensatory Mitigation for Marine Bycatch a Sufficient Conservation Measure for Long-Lived Seabirds?

Along the lines of the ‘polluter pays principle’, it has recently been proposed that the local long-line fishing industry should fund eradication of terrestrial predators at seabird breeding colonies, as a compensatory measure for the bycatch caused by the fishing activity. The measure is economically sound, but a quantitative and reliable test of its biological efficacy has never been conducted. Here, we investigated the demographic consequences of predator eradication for Cory's shearwater Calonectris diomedea, breeding in the Mediterranean, using a population model that integrates demographic rates estimated from individual life-history information with experimental measures of predation and habitat structure. We found that similar values of population growth rate can be obtained by different combinations of habitat characteristics, predator abundance and adult mortality, which explains the persistence of shearwater colonies in islands with introduced predators. Even so, given the empirically obtained values of survival, all combinations of predator abundance and habitat characteristics projected a decline in shearwater numbers. Perturbation analyses indicated that the value and the sensitivity of shearwater population growth rates were affected by all covariates considered and their interactions. A decrease in rat abundance delivered only a small increase in the population growth rate, whereas a change in adult survival (a parameter independent of rat abundance) had the strongest impact on population dynamics. When adult survival is low, rat eradication would allow us to “buy” years before extinction but does not reverse the process. Rat eradication can therefore be seen as an emergency measure if threats on adult survival are eliminated in the medium-term period. For species with low fecundity and long life expectancy, our results suggest that rat control campaigns are not a sufficient, self-standing measure to compensate the biological toll of long-line fisheries

Inferring transient dynamics of human populations from matrix non-normality

This is the final version of the article. Available from Springer Verlag via the DOI in this record.In our increasingly unstable and unpredictable world, population dynamics rarely settle uniformly to long-term behaviour. However, projecting period-by-period through the preceding fluctuations is more data-intensive and analytically involved than evaluating at equilibrium. To efficiently model populations and best inform policy, we require pragmatic suggestions as to when it is necessary to incorporate short-term transient dynamics and their effect on eventual projected population size. To estimate this need for matrix population modelling, we adopt a linear algebraic quantity known as non-normality. Matrix non-normality is distinct from normality in the Gaussian sense, and indicates the amplificatory potential of the population projection matrix given a particular population vector. In this paper, we compare and contrast three well-regarded metrics of non-normality, which were calculated for over 1000 age-structured human population projection matrices from 42 European countries in the period 1960 to 2014. Non-normality increased over time, mirroring the indices of transient dynamics that peaked around the millennium. By standardising the matrices to focus on transient dynamics and not changes in the asymptotic growth rate, we show that the damping ratio is an uninformative predictor of whether a population is prone to transient booms or busts in its size. These analyses suggest that population ecology approaches to inferring transient dynamics have too often relied on suboptimal analytical tools focussed on an initial population vector rather than the capacity of the life cycle to amplify or dampen transient fluctuations. Finally, we introduce the engineering technique of pseudospectra analysis to population ecology, which, like matrix non-normality, provides a more complete description of the transient fluctuations than the damping ratio. Pseudospectra analysis could further support non-normality assessment to enable a greater understanding of when we might expect transient phases to impact eventual population dynamics.This work was funded by Wellcome Trust New Investigator 103780 to TE, who is also funded by NERC Fellowship NE/J018163/1. JB gratefully acknowledges the ESRC Centre for Population Change ES/K007394/1

Analysis of lethal and sublethal impacts of environmental disasters on sperm whales using stochastic modeling

Mathematical models are essential for combining data from multiple sources to quantify population endpoints. This is especially true for species, such as marine mammals, for which data on vital rates are difficult to obtain. Since the effects of an environmental disaster are not fixed, we develop time-varying (nonautonomous) matrix population models that account for the eventual recovery of the environment to the pre-disaster state. We use these models to investigate how lethal and sublethal impacts (in the form of reductions in the survival and fecundity, respectively) affect the population’s recovery process. We explore two scenarios of the environmental recovery process and include the effect of demographic stochasticity. Our results provide insights into the relationship between the magnitude of the disaster, the duration of the disaster, and the probability that the population recovers to pre-disaster levels or a biologically relevant threshold level. To illustrate this modeling methodology, we provide an application to a sperm whale population. This application was motivated by the 2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico that has impacted a wide variety of species populations including oysters, fish, corals, and whales

Relative nutritional quality of C 3 and C 4 grasses for a graminivorous lepidopteran, Paratrytone melane (Hesperiidae)

We tested the hypothesis that C 4 grasses are inferior to C 3 grasses as host plants for herbivorous insects by measuring the relative performance of larvae of a graminivorous lepidopteran, Paratrytone melane (Hesperiidae), fed C 3 and C 4 grasses. Relative growth rates and final weights were higher in larvae fed a C 3 grass in Experiment I. However, in two additional experiments, relative growth rates and final weights were not significantly different in larvae fed C 3 and C 4 grasses. We examined two factors which are believed to cause C 4 grasses to be of lower nutritional value than C 3 grasses: foliar nutrient levels and nutrient digestibility. In general, foliar nutrient levels were higher in C 3 grasses. In Experiment I, protein and soluble carbohydrates were digested from a C 3 and a C 4 grass with equivalent efficiencies. Therefore, differences in larval performance are best explained by higher nutrient levels in the C 3 grass in this experiment. In Experiment II, soluble carbohydrates were digested with similar efficiencies from C 3 and C 4 grasses but protein was digested with greater efficiency from the C 3 grasses. We conclude (1) that the bundle sheath anatomy of C 4 grasses is not a barrier to soluble carbohydrate digestion and does not have a nutritionally significant effect on protein digestion and (2) that P. melane may consume C 4 grasses at compensatory rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47798/1/442_2004_Article_BF00317268.pd

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Comparative Geno-Plasticity Analysis of Mycoplasma bovis HB0801 (Chinese Isolate)

Mycoplasma bovis pneumonia in cattle has been epidemic in China since 2008. To investigate M. bovis pathogenesis, we completed genome sequencing of strain HB0801 isolated from a lesioned bovine lung from Hubei, China. The genomic plasticity was determined by comparing HB0801 with M. bovis strain ATCC® 25523™/PG45 from cow mastitis milk, Chinese strain Hubei-1 from lesioned lung tissue, and 16 other Mycoplasmas species. Compared to PG45, the genome size of HB0801 was reduced by 11.7 kb. Furthermore, a large chromosome inversion (580 kb) was confirmed in all Chinese isolates including HB0801, HB1007, a strain from cow mastitis milk, and Hubei-1. In addition, the variable surface lipoproteins (vsp) gene cluster existed in HB0801, but contained less than half of the genes, and had poor identity to that in PG45, but they had conserved structures. Further inter-strain comparisons revealed other mechanisms of gene acquisition and loss in HB0801 that primarily involved insertion sequence (IS) elements, integrative conjugative element, restriction and modification systems, and some lipoproteins and transmembrane proteins. Subsequently, PG45 and HB0801 virulence in cattle was compared. Results indicated that both strains were pathogenic to cattle. The scores of gross pathological assessment for the control group, and the PG45- and HB0801-infected groups were 3, 13 and 9, respectively. Meanwhile the scores of lung lesion for these three groups were 36, 70, and 69, respectively. In addition, immunohistochemistry detection demonstrated that both strains were similarly distributed in lungs and lymph nodes. Although PG45 showed slightly higher virulence in calves than HB0801, there was no statistical difference between the strains (P>0.05). Compared to Hubei-1, a total of 122 SNP loci were disclosed in HB0801. In conclusion, although genomic plasticity was thought to be an evolutionary advantage, it did not apparently affect virulence of M. bovis strains in cattle

A large age for the pulsar B1757-24 from an upper limit on its proper motion

The "characteristic age" of a pulsar usually is considered to approximate its true age, but this assumption has led to some puzzling results, including the fact that many pulsars with small characteristic ages have no associated supernova remnants. The pulsar B1757-24 is located just beyond the edge of a supernova remnant; the properties of the system indicate that the pulsar was born at the centre of the remnant, but that it has subsequently overtaken the expanding blast-wave. With a characteristic age of 16,000 yr, this implies an expected proper motion by the pulsar of 63-80 milliarcsec per year. Here we report observations of the nebula surrounding the pulsar which limit its proper motion to less than 25 mas/yr, implying a minimum age of 39,000 yr. A more detailed analysis argues for a true age as great as 170,000 yr, significantly larger than the characteristic age. From this result and other discrepancies associated with pulsars, we conclude that characteristic ages seriously underestimate the true ages of pulsars