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Biomedical subjects

M J Wade

Publications and source records attributed to M J Wade.

At least 19 recordsLinked to original sources

The effect of delayed visual feedback on telerobotic surgery.

BACKGROUND: Telerobotic surgery is ideally suited for remote applications in which the instrument control console is stationed separately from the end-effectors at the patient's bedside. However, if the distance between the console and the patient is great enough, a lag effect or latency between end-effector manipulation and the depicted image leads to alterations in movement patterns. The purpose of this study was to determine the effect of visual delay on surgical task performance. METHODS: At an endoscopic skill station, an analogue delay device was interposed between the surgical field and monitor to delay the transmission of visual information, thus mimicking the distance effect of data transmission. Three surgeons with similar laparoscopic experience participated in the laparoscopic knot tying portion of the study, and seven residents participated in the accuracy and dexterity tasks. The time to complete a single throw was recorded in seconds after adding consecutively increasingly time delay in 50 ms increments. Similar time delay increments were added for the accuracy and dexterity tasks, which involved passing a needle through two adjacent circles and passing a small cylinder through a larger one to reproduce two-handed coordination and spatial resolution. Data were presented as the median time to complete each task. RESULTS: For all three tasks, an incremental increase in time delay was associated with a significant (p < 0.001) increase in the time to complete the task. For dexterity, a statistically significant (p <or= 0.05) delay was identified at 0.25 s of delay from control values without delay. A move-and-wait strategy was gradually adopted up to 0.4 s of visual delay. CONCLUSIONS: Compensation for visually delayed image perception occurs on several levels. Initial adaptations include slower end-effector manipulation; late adaptive changes include a move-and-wait strategy. Increased time to perform surgical maneuvers as well as diminished accuracy, diminished dexterity, and increasing fatigue represent additional performance encumbrances evoked by visual time delay. The nuances of both human and digital compensatory mechanisms for visual time delay must be defined and enhanced to maximize the potential for telerobotic surgical applications.

Adaptation, Physiological↗

Spread of parasites in metapopulations: an experimental study of the effects of host migration rate and local host population size.

We established experimental metapopulations of the flour beetle, Tribolium castaneum, and its ectoparasitic mite, Acarophenax tribolii, to investigate the effects of host migration rate and local host population size on the spread of mite infections. Global prevalence across our metapopulations was less than half the observed within-patch prevalence, so that spatial structure alone afforded a great deal of protection to hosts against parasite infection. Our results showed further that migration played a determining role in occupancy, the number of patches infected within a metapopulation, while host population size played a determining role in local prevalence, the fraction of hosts infected within local patches. Local and global prevalence appeared to reach equilibrium levels on 2 different time-scales. Local host prevalence reached equilibrium values within 30 days of receiving an infected host migrant. Global prevalence increased more slowly and was clearly dependent upon occupancy, the number of host patches with at least 1 infected host, which in turn depended on the level of host migration among host patches. The effect of population size was not limited to local prevalence in patches without spatial structure but extended to sets of patches across the metapopulation. Lloyd's index of patchiness differed significantly between metapopulations with small versus large numbers of hosts. Although parasites were aggregated on hosts for both local patch sizes, they tended to aggregate to a much greater degree at the smaller host patch size. We discuss our empirical findings in light of current epidemiological theory.

Animals↗

Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease.

OBJECTIVES: To determine whether nondemented subjects with pathological evidence of preclinical Alzheimer disease (AD) demonstrate neuronal loss in the entorhinal cortex and hippocampus, and whether the onset of cognitive deficits in AD coincides with the onset of neuronal degeneration. METHODS: Preclinical AD cases have been defined by the absence of cognitive decline but with neuropathological evidence of AD. The hippocampus and entorhinal cortex were examined in 13 nondemented cases (Clinical Dementia Rating [CDR] 0) with healthy brains, 4 cases with preclinical AD, 8 cases with very mild symptomatic AD (CDR 0.5), and 4 cases with severe AD (CDR 3, hippocampus only). The volume and number of neurons were determined stereologically in 2 areas that are vulnerable to AD--the entorhinal cortex (as a whole and layer II alone) and hippocampal field CA1. RESULTS: There was no significant decrease in neuron number or volume with age in the healthy nondemented group and little or none between the healthy and preclinical AD groups. Substantial decreases were found in the very mild AD group in neuron number (35% in the entorhinal cortex, 50% in layer II, and 46% in CA1) and volume (28% in the entorhinal cortex, 21% in layer II, and 29% in CA1). Greater decrements were observed in CA1 in the severe AD group. CONCLUSIONS: There is little or no neuronal loss in aging or preclinical AD but substantial loss in very mild AD. The findings indicate that AD results in clinical deficits only when it produces significant neuronal loss.

Aged↗

Maternal effect genes and the evolution of sociality in haplo-diploid organisms.

Maternal care and female-biased sex ratios are considered by many to be essential prerequisites for the evolution of eusocial behaviors among the hymenoptera. Using population genetic models, I investigate the evolution of genes that have positive maternal effects but negative, direct effects on offspring fitness. I find that, under many conditions, such genes evolve more easily in haplo-diploids than in diplo-diploids. In fact, the conditions are less restrictive than those of kin selection theory, which postulate genes with negative direct effects but positive sib-social effects. For example, the conditions permitting the evolution of maternal effect genes are not affected if females mate multiply, whereas multiple mating reduces the efficacy of kin selection by reducing genetic relatedness within colonies. Inbreeding also differentially facilitates evolution of maternal effect genes in haplo-diploids relative to diplo-diploids, although it does not differentially affect the evolution of sib-altruism genes. Furthermore, when the direct, deleterious pleiotropic effect is restricted to sons, a maternal effect gene can evolve when the beneficial maternal effect is less than half (with inbreeding, much less) of the deleterious effect on sons. For kin selection, however, the sib-social benefits must always exceed the direct costs because genetic relatedness is always less than or equal to 1.0. The results suggest that haplo-diploidy facilitates (1) the evolution of maternal care, and (2) the evolution of maternal effect genes with antagonistic pleiotropic effects on sons. The latter effect may help explain the tendency toward female-biased sex ratios in haplo-diploids, especially those with inbreeding. I conclude that haplo-diploidy not only facilitates the evolution of sister-sister altruism by kin selection but also facilitates the evolution of maternal care and female-biased sex ratios, two prerequisites for eusociality.

Alleles↗

Cultural inheritance as a mechanism for population sex-ratio bias in reptiles.

Although natural populations of most species exhibit a 1:1 sex ratio, biased sex ratios are known to be associated with non-Mendelian inheritance, as in sex-linked meiotic drive and cytoplasmic inheritance (Charnov 1982; Hurst 1993). We show how cultural inheritance, another type of non-Mendelian inheritance, can favor skewed primary sex ratios and propose that it may explain the female-biased sex ratios commonly observed in reptiles with environmental sex determination (ESD). Like cytoplasmic elements, cultural traits can be inherited through one sex. This, in turn, favors skewing the primary sex allocation in favor of the transmitting sex. Female nest-site philopatry is a sex-specific, culturally inherited trait in many reptiles with ESD and highly female-biased sex ratios. We propose that the association of nest-site selection with ESD facilitates the maternal manipulation of offspring sex ratios toward females.

Animals↗

Epistasis, complex traits, and mapping genes.

Using a three-locus model wherein two loci regulate a third, candidate locus, I examine physiological epistasis from the 'gene's eye view' of the regulated locus. I show that, depending upon genetic background at the regulatory loci, an allele at the candidate locus can be dominant, additive, recessive, neutral, over-dominant, or under-dominant in its effects on fitness. This kind of variation in allelic effect caused by variation in genetic background from population to population, from time to time in the same population, or sample to sample makes finding and mapping the genes underlying a complex phenotype difficult. The rate of evolution of such genes can also be slowed, especially in genetically subdivided metapopulations with migration. Nevertheless, understanding how variation in genetic background causes variation in allelic effects permits the genetic architecture of such complex traits to be dissected into the interacting component genes. While some backgrounds diminish allelic effects and make finding and mapping genes difficult, other backgrounds enhance allelic effects and facilitate gene mapping.

Alleles↗

Molecular evolution near a two-locus balanced polymorphism.

Balancing selection at one locus can increase the amount of selectively neutral variation within neighboring genomic regions. Discrete phenotypic polymorphisms studied in natural populations are frequently determined by sets of interacting genes instead of alternative alleles at single loci. We extend coalescent theory to investigate balancing selection on combinations of linked genes. We find that variation at neutral sites is increased across a much larger genomic region relative to the single-locus models: the entire region lying between the two loci in balanced combination is affected to some degree. Epistatic selection maintains these high levels of neutral variation because it directly opposes the homogenizing effect of recombination. The results of the theory are discussed in relation to published gene sequence data, primarily from Drosophila.

Alleles↗

Early invasive versus ischaemia-guided strategies in the management of non-Q wave myocardial infarction patients with and without prior myocardial infarction; results of Veterans Affairs Non-Q Wave Infarction Strategies in Hospital (VANQWISH) trial.

AIMS: To compare the role of early invasive vs conservative management strategies in treating patients with non-Q wave myocardial infarction with or without a prior myocardial infarction. BACKGROUND: In patients recovering from non-Q wave myocardial infarction, the prognosis among patients with a first non-Q wave myocardial infarction is significantly better than in patients with a prior myocardial infarction, yet physicians often adopt an early invasive strategy to treat patients with a first non-Q wave myocardial infarction. METHODS: Non-Q wave myocardial infarction patients enrolled in the VANQWISH trial with a history of prior myocardial infarction were compared to those with a first non-Q wave myocardial infarction, for the trial primary end-point of death or myocardial infarction at 1 and 12 months, as well as for the initial randomized treatment strategy. RESULTS: Of the 920 non-Q wave myocardial infarction patients, 396 had a history of prior myocardial infarction and 524 did not. Patients with a history of prior myocardial infarction were older and had a higher incidence of multiple high-risk baseline characteristics than those with a first non-Q wave myocardial infarction. Compared to the group with a first myocardial infarction, the prior myocardial infarction group suffered more events at both 1 month (11% vs 6%, P=0.007) and at 12 months (29% vs 16%, P<0.001). This difference in outcome remained significant even after adjusting for confounding variables (P<0.0001 at 12 months). Among the non-Q wave myocardial infarction patients with a prior myocardial infarction, the frequency of death or recurrent myocardial infarction was similar in both invasive and conservative groups during the first year of follow-up. Among the first non-Q wave myocardial infarction group, those assigned to the conservative strategy had significantly fewer events (3% vs 9%, P=0.009 at 1 month; 12% vs 20%, P=0.016 at 12 months) and mortality (1% vs 5%, P=0.012 at one month; 5% vs 11%, P=0.009 at 12 months) than those assigned to early invasive strategy. CONCLUSION: A history of prior myocardial infarction identifies a moderately high-risk subset of non-Q wave myocardial infarction patients who display similar long-term outcomes regardless of the strategy assignment; however, patients with a first non-Q wave myocardial infarction may fare better with a conservative or ischaemia-guided approach during the first post infarction year.

Aged↗

Opposing levels of selection can cause neutrality: mating patterns and maternal-fetal interactions.

A biallelic viability model based on human data for maternal-fetal interactions reported by Hedrick (1997) gives the interesting result of neutral stability at all gene frequencies. I show that there are two levels of selection, within and among families, acting in opposing directions in this model and that the neutral stability occurs when the two levels of selection exactly balance one another, as they do in a randomly mating population. Deviations from random mating disrupt the balance and consequently destroy the neutral stability. However, with inbreeding avoidance, which characterizes the human histocompatibility loci, within-family selection is strengthened and among-family selection is weakened. This favors the invasion of new alleles and contributes to a high equilibrium level of genetic diversity at loci with maternal-fetal interactions affecting offspring viability in the pattern described by Hedrick. This pattern of selection is remarkably similar to that observed for the maternal effect selfish genes, Medea in flour beetles and scat in the mouse, and the Gp-9 gene in the fire ant.

Alleles↗

Genetic variation segregating in natural populations of Tribolium castaneum affecting traits observed in hybrids with T. freemani.

We investigated patterns of within-species genetic variation for traits observed in hybrids (hybrid numbers, hybrid sex ratios, and hybrid male deformities) between two species of flour beetles, Tribolium castaneum and T. freemani. We found genetic variation segregating among four natural populations of T. castaneum as well as within these populations. For some hybrid traits, we observed as much variation among populations 750 km apart as between populations on different continents, suggesting genetic differentiation at a local scale. Within natural populations, the variation segregating among sires is greater than that found in an earlier study for an outbred laboratory population and comparable to that observed between inbred lines derived from the outbred stock by eight generations of brother-sister mating. When sires from T. castaneum are mated to conspecific and heterospecific females, we do not observe a significant correlation at the level of the family mean between the intraspecific and interspecific phenotypes, suggesting the independence of the hybrid traits from comparable traits within species. We discuss our findings in relation to the evolutionary genetics of speciation and the expression of epistatic genetic variance in interspecific crosses.

Animals↗

An improved microinjection protocol for the transfer of Wolbachia pipientis between infected and uninfected strains of the flour beetle Tribolium confusum.

The lethality of halocarbon and other oils to hatching larvae of the flour beetle Tribolium confusum limits existing microinjection protocols, because postinjection survivorship is only 5.6% of the eggs injected. We report the development of an oil-free protocol that improves survivorship fivefold. We used this protocol to transfect the cytoplasmic endosymbiont Wolbachia pipientis from infected donor eggs to uninfected host eggs and observed reproductive incompatibility in 40% of the surviving, injected eggs. Compared with mock injected controls (35.9% survival) or microinjection of uninfected cytoplasm (32.3% survival), injection of Wolbachia-infected cytoplasm into host eggs significantly reduced egg-to-adult survival (25.1%).

Animals↗

Conditions for soft selection favoring the evolution of hybrid inviability.

Hybrid inviability per se is not generally considered adaptive; it is believed to evolve as a pleiotropic consequence of other genetic changes, either adaptive or neutral, between diverging populations. However, given the pre-existence of hybrid sterility, there are circumstances under which hybrid inviability may be directly selected. In this report, we model the evolution of hybrid inviability in the context of within-family density-dependent selection (soft selection). This paper shows that under certain conditions, an allele causing hybrid inviability can increase when rare, despite also decreasing viability in conspecifics. These conditions depend upon the strength of density effects within families and upon the frequency of matings with heterospecifics. It is found that, under the most favorable conditions (strong soft selection and frequent hybridization), the inviability allele can invade when its deleterious effect on the hybrid viability exceeds four times its deleterious effects on conspecific heterozygotes. The conditions for fixation of the allele are also investigated and the circumstances under which this process might operate in natural populations are discussed. The conclusion is that the most restrictive condition is that for this process to evolve, there must be little opportunity for postzygotic reproductive isolation to evolve.

Alleles↗

Increased male fertility in Tribolium confusum beetles after infection with the intracellular parasite Wolbachia.

The cytoplasmically inherited microorganism Wolbachia pipientis behaves like a sexually selected trait in its host, the flour beetle Tribolium confusum, enhancing male fertility at the expense of female fecundity. Here we show that infected females have fewer offspring than uninfected females but infected males have a large fertility advantage over uninfected males within multiply-inseminated infected or uninfected females. The male fertility effect accelerates the spread of the Wolbachia through the host population and expands the initial opportunity for hitch-hiking of host nuclear genes. Sperm competition in a host, mediated by endosymbionts, has not been previously described.

Animals↗

Incipient speciation in the flour beetle, Tribolium confusum: premating isolation between natural populations.

We report the existence of partial reproductive isolation between two natural populations of the flour beetle, Tribolium confusum, collected in Kaduna, Nigeria and Zagreb, Croatia. When a female from either population is paired with a single sympatric or allopatric male, she produces near normal numbers of semifertile offspring. However, when females are multiply mated with allopatric and sympatric males, the sympatric males sire the large majority of offspring. When measured in offspring numbers, the mean relative fitness of allopatric males is 0.425 with Nigerian females and 0.085 with Croatian females. Thus, the reproductive isolation is reciprocal but asymmetric. Behavioural observations indicate that only a fraction of mating attempts by allopatric males are successful because females do not become quiescent as often when mounted by allopatric males. The premating isolation is also reciprocal but asymmetric: Nigerian females are more accepting of allopatric males as mates than are Croatian females. The prezygotic behavioural isolation between these two populations is different from the postmating, prezygotic isolation observed between two other species in the genus, T. castaneum and T. freemani. Furthermore, the T. confusum interpopulation hybrids are fertile although they exhibit a weak female bias.

Animals↗

The effect of population subdivision on the rate of spread of parasite-mediated cytoplasmic incompatibility.

Over 20 species of arthropods are known to harbor an endosymbiotic bacterium, Wolbachia associated with partial reproductive incompatibility. The micro-organism spreads through a random mating population with positive frequency dependence. Many insect populations, however, are subdivided to some degree. In this paper we model the effect of population subdivision on the rate of spread of Wolbachia and show that it slows the rate of spread of the micro-organism but by itself cannot cause a stable polymorphism. The effects of the micro-organism on host fitness, partial incompatibility, and environmental curing are also investigated, both for panmictic and subdivided populations. In all cases, population subdivision slows the rate of spread relative to a panmictic population, but does not produce a stable polymorphism of infection.

Animals↗