Shorter time to diagnosis and improved stage at presentation in Swiss patients with retinoblastoma treated from 1963 to 2004

Rapport de synthèse : Le rétinoblastome est la tumeur de l'oeil la plus fréquente chez l'enfant. Un diagnostic précoce est important pour sauver le globe oculaire et la survie du patient. Le but de notre étude est de déterminer l'évolution de l'intervalle diagnostique, c'est-à-dire le délai entre les premiers symptômes et la date du diagnostic officiel du rétinoblastome, sur une période de 40 ans en Suisse. Matériel et méthode : Il s'agit d'une étude rétrospective faite sur 139 patients suisses traités pour rétinoblastome durant trois différentes périodes : (1) 1963-1983 ; (2) 1984-1993 ; et (3) 1994-2004. On compare certaines caractéristiques : le sexe du patient, la latéralité de la maladie, les premiers symptômes, leurs observateurs, l'intervalle diagnostique, l'âge au diagnostic, le stade de la maladie, l'histoire familiale. Résultats : 37 patients (26.6%) ont été traités dans la première période ; 44 (31.7%) dans la période 2 et 58 (41.7%) dans la période 3. L'intervalle diagnostique diminue de façon significative de 6.97 mois dans la période 1 à 3.58 dans la période 2 à 2.25 dans la période 3 pour le total des malades. Ceci reste significatif pour les rétinoblastomes unilatéraux. De plus, dans ce même groupe, on observe une diminution significative des stades avancés de la maladie, groupe E selon Murphree (61.5% dans la période 1 ; 46.7% dans la période 2 et 22.2 % dans la période 3). Lorsque la maladie est bilatérale, les mêmes observations se font de façon un peu moins marquée. Il n'y a aucun patient diagnostiqué au stade E de la maladie en présence d'une anamnèse familiale positive. Leucocorie (48.2%) et strabisme (20.1 %) sont les symptômes les plus fréquents durant les 3 périodes. Les seuls facteurs qui influencent significativement le risque d'avoir un stade E de la maladie sont la durée de l'intervalle diagnostic et la période de diagnostic. Conclusion : On constate un progrès dans le diagnostic du rétinoblastome en Suisse, surtout lors de maladie unilatérale. De même, des améliorations sont notées dans la maladie bilatérale mais de façon non significative. Il est donc important de mieux enseigner aux médecins à reconnaître les symptômes oculaires de la maladie et à référer les patients plus tôt aux spécialistes. Abstract : OBECTIVES : Retinoblastoma is the most frequent intraocular malignancy in children. Early diagnosis is essential for globe salvage and patient survival. The aim of our study was to determine how time to diagnosis of retinoblastoma has evolved over a 40-year period in Switzerland. METHOD AND PATIENTS : A retrospective study of 139 Swiss patients with retinoblastoma was performed comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors taken into account were gender, laterality of retínoblastoma, age at first symptoms, type and first observer of symptoms, time to diagnosis, age at diagnosis, disease stage, and family history. RESULTS : Thirty-seven patients (26.6%) were treated in period 1, 44 (31.7%) in period 2, and S8 (41.7%) in period 3.Overall, the diagnostic interval decreased in a significant way from 6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking separately at unilateral and bilateral disease, the decrease oí the diagnostic interval remained statistically significant in unilateral retinoblastoma; there was also a significant reduction in the number of patients with advanced group E disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in period 3). In bilateral disease, the same observations were made to a lesser extent. However, there were no cases with group E disease in 10 patients with positive family history. Leukornria (48.2%) and strabismus (20.1 %) were the 2 most frequent symptoms throughout the 3 periods. The only factors that statistically influenced the chances of having a diagnosis of group E disease were the diagnostic interval and period of diagnosis. Conclusion : Progress has been made in the diagnosis of retinoblastoma in Switzerland, notably in unilateral disease. Improvement to a lesser extent has also been observed in bilateral cases but without statistical significance. Greater effort is needed to teach physians-in-training to recognize the importance of ocular symptoms and refer patients earlier.

Geographical and temporal body size variation in a reptile: roles of sex, ecology, phylogeny and ecology structured in phylogeny.

Geographical body size variation has long interested evolutionary biologists, and a range of mechanisms have been proposed to explain the observed patterns. It is considered to be more puzzling in ectotherms than in endotherms, and integrative approaches are necessary for testing non-exclusive alternative mechanisms. Using lacertid lizards as a model, we adopted an integrative approach, testing different hypotheses for both sexes while incorporating temporal, spatial, and phylogenetic autocorrelation at the individual level. We used data on the Spanish Sand Racer species group from a field survey to disentangle different sources of body size variation through environmental and individual genetic data, while accounting for temporal and spatial autocorrelation. A variation partitioning method was applied to separate independent and shared components of ecology and phylogeny, and estimated their significance. Then, we fed-back our models by controlling for relevant independent components. The pattern was consistent with the geographical Bergmann's cline and the experimental temperature-size rule: adults were larger at lower temperatures (and/or higher elevations). This result was confirmed with additional multi-year independent data-set derived from the literature. Variation partitioning showed no sex differences in phylogenetic inertia but showed sex differences in the independent component of ecology; primarily due to growth differences. Interestingly, only after controlling for independent components did primary productivity also emerge as an important predictor explaining size variation in both sexes. This study highlights the importance of integrating individual-based genetic information, relevant ecological parameters, and temporal and spatial autocorrelation in sex-specific models to detect potentially important hidden effects. Our individual-based approach devoted to extract and control for independent components was useful to reveal hidden effects linked with alternative non-exclusive hypothesis, such as those of primary productivity. Also, including measurement date allowed disentangling and controlling for short-term temporal autocorrelation reflecting sex-specific growth plasticity.

Comparative testing of a miniature diffusion size classifier to assess airborne ultrafine particles under field conditions

Miniature diffusion size classifiers (miniDiSC) are novel handheld devices to measure ultrafine particles (UFP). UFP have been linked to the development of cardiovascular and pulmonary diseases; thus, detection and quantification of these particles are important for evaluating their potential health hazards. As part of the UFP exposure assessments of highwaymaintenance workers in western Switzerland, we compared a miniDiSC with a portable condensation particle counter (P-TRAK). In addition, we performed stationary measurements with a miniDiSC and a scanning mobility particle sizer (SMPS) at a site immediately adjacent to a highway. Measurements with miniDiSC and P-TRAK correlated well (correlation of r = 0.84) but average particle numbers of the miniDiSC were 30%âeuro"60% higher. This difference was significantly increased for mean particle diameters below 40 nm. The correlation between theminiDiSC and the SMPSduring stationary measurements was very high (r = 0.98) although particle numbers from the miniDiSC were 30% lower. Differences between the three devices were attributed to the different cutoff diameters for detection. Correction for this size dependent effect led to very similar results across all counters.We did not observe any significant influence of other particle characteristics. Our results suggest that the miniDiSC provides accurate particle number concentrations and geometric mean diameters at traffic-influenced sites, making it a useful tool for personal exposure assessment in such settings.

Sudden weather deterioration but not brood size affects baseline corticosterone levels in nestling Alpine swifts.

While evidence is accumulating that stress-induced glucocorticoid responses help organisms to quickly adjust their physiology and behaviour to life-threatening environmental perturbations, the function and the ecological factors inducing variation in baseline glucocorticoid levels remain poorly understood. In this study we investigated the effects of brood size by experimentally manipulating the number of nestlings per brood and the effect of weather condition on baseline corticosterone levels of nestling Alpine swifts (Apus melba). We also examined the potential negative consequences of an elevation of baseline corticosterone on nestling immunity by correlating corticosterone levels with ectoparasite intensity and the antibody production towards a vaccine. Although nestlings reared in enlarged broods were in poorer condition than nestlings reared in reduced broods, they showed similar baseline corticosterone levels. In contrast, nestling baseline corticosterone levels were higher immediately after cold and rainy episodes with strong winds. Neither nestling infestation rate by ectoparastic flies nor nestling antibody production against a vaccine was correlated with baseline corticosterone levels. Thus, our results suggest that altricial Alpine swift nestlings can quickly modulate baseline corticosterone levels in response to unpredictable variations in meteorological perturbation but not to brood size which may be associated with the degree of sibling competition. Apparently, short-term elevations of baseline corticosterone have no negative effects on nestling immunocompetence.

Fitness and the level of homozygosity in a social insect.

To date very few studies have addressed the effects of inbreeding in social Hymenoptera, perhaps because the costs of inbreeding are generally considered marginal owing to male haploidy whereby recessive deleterious alleles are strongly exposed to selection in males. Here, we present one of the first studies on the effects of queen and worker homozygosity on colony performance. In a wild population of the ant Formica exsecta, the relative investment of single-queen colonies in sexual production decreased with increased worker homozygosity. This may either stem from increased homozygosity decreasing the likelihood of diploid brood to develop into queens or a lower efficiency of more homozygous workers at feeding larvae and thus a lower proportion of the female brood developing into queens. There was also a significant negative association between colony age and the level of queen but not worker homozygosity. This association may stem from inbreeding affecting queen lifespan and/or their fecundity, and thus colony survival. However, there was no association between queen homozygosity and colony size, suggesting that inbreeding affects colony survival as a result of inbred queens having a shorter lifespan rather than a lower fecundity. Finally, there was no significant association between either worker or queen homozygosity and the probability of successful colony founding, colony size and colony productivity, the three other traits studied. Overall, these results indicate that inbreeding depression may have important effects on colony fitness by affecting both the parental (queen) and offspring (worker)generations cohabiting within an ant colony.

Length of activity season drives geographic variation in body size of a widely distributed lizard

Understanding the factors that drive geographic variation in life history is an important challenge in evolutionary ecology. Here, we analyze what predicts geographic variation in life-history traits of the common lizard, Zootoca vivipara, which has the globally largest distribution range of all terrestrial reptile species. Variation in body size was predicted by differences in the length of activity season, while we found no effects of environmental temperature per se. Females experiencing relatively short activity season mature at a larger size and remain larger on average than females in populations with relatively long activity seasons. Interpopulation variation in fecundity was largely explained by mean body size of females and reproductive mode, with viviparous populations having larger clutch size than oviparous populations. Finally, body size-fecundity relationship differs between viviparous and oviparous populations, with relatively lower reproductive investment for a given body size in oviparous populations. While the phylogenetic signal was weak overall, the patterns of variation showed spatial effects, perhaps reflecting genetic divergence or geographic variation in additional biotic and abiotic factors. Our findings emphasize that time constraints imposed by the environment rather than ambient temperature play a major role in shaping life histories in the common lizard. This might be attributed to the fact that lizards can attain their preferred body temperature via behavioral thermoregulation across different thermal environments. Length of activity season, defining the maximum time available for lizards to maintain optimal performance, is thus the main environmental factor constraining growth rate and annual rates of mortality. Our results suggest that this factor may partly explain variation in the extent to which different taxa follow ecogeographic rules.

Sample size and statistical power in the hierarchical analysis of variance: applications in morphometry of the nervous system.

Analysis of variance is commonly used in morphometry in order to ascertain differences in parameters between several populations. Failure to detect significant differences between populations (type II error) may be due to suboptimal sampling and lead to erroneous conclusions; the concept of statistical power allows one to avoid such failures by means of an adequate sampling. Several examples are given in the morphometry of the nervous system, showing the use of the power of a hierarchical analysis of variance test for the choice of appropriate sample and subsample sizes. In the first case chosen, neuronal densities in the human visual cortex, we find the number of observations to be of little effect. For dendritic spine densities in the visual cortex of mice and humans, the effect is somewhat larger. A substantial effect is shown in our last example, dendritic segmental lengths in monkey lateral geniculate nucleus. It is in the nature of the hierarchical model that sample size is always more important than subsample size. The relative weight to be attributed to subsample size thus depends on the relative magnitude of the between observations variance compared to the between individuals variance.

Melanin-based coloration covaries with ovary size in an age-specific manner in the barn owl.

While the adaptive function of black eumelanin-based coloration is relatively well known, the function of reddish-brown pheomelanin-based coloration is still unclear. Only a few studies have shown or suggested that the degree of reddish-brownness is associated with predator-prey relationships, reproductive parameters, growth rate and immunity. To gain insight into the physiological correlates of melanin-based coloration, I collected barn owl (Tyto alba) cadavers and examined the covariation between this colour trait and ovary size, an organ that increases in size before reproduction. A relationship is expected because melanin-based coloration often co-varies with sexual activity. The results showed that reddish-brown juveniles had larger ovaries than whiter juveniles particularly in individuals in poor condition and outside the breeding season, while in birds older than 2 years lightly coloured females had larger ovaries than reddish-brown conspecifics. As barn owls become less reddish-brown between the first and second year of age, the present study suggests that reddish-brown pheomelanic and whitish colorations are associated with juvenile- and adult-specific adaptations, respectively.

What makes a host profitable? Parasites balance host nutritive resources against immunity.

Numerous host qualities can modulate parasite fitness, and among these, host nutritive resources and immunity are of prime importance. Indeed, parasite fitness increases with the amount of nutritive resources extracted from the host body and decreases with host immune response. To maximize fitness, parasites have therefore to balance these two host components. Yet, because host nutritive resources and immunity both increase with host body condition, it is unclear whether parasites perform better on hosts in prime, intermediate, or poor condition. We investigated blood meal size and survival of the ectoparasitic louse fly Crataerina melbae in relation to body condition and cutaneous immune response of their Alpine swift (Apus melba) nestling hosts. Louse flies took a smaller blood meal and lived a shorter period of time when feeding on nestlings that were experimentally food deprived or had their cutaneous immune response boosted with methionine. Consistent with these results, louse fly survival was the highest when feeding on nonexperimental nestlings in intermediate body condition. Our findings emphasize that although hosts in poor condition had a reduced immunocompetence, parasites may have avoided them because individuals in poor condition did not provide adequate resources. These findings highlight the fact that giving host immunocompetence primary consideration can result in a biased appraisal of host-parasite interactions.

Population density and optimal body size.

The population density of an organism is one of the main aspects of its environment, and shoud therefore strongly influence its adaptive strategy. The r/K theory, based on the logistic model, was developed to formalize this influence. K-selectioon is classically thought to favour large body sizes. This prediction, however, cannot be directly derived from the logistic model: some auxiliary hypotheses are therefor implicit. These are to be made explicit if the theory is to be tested. An alternative approach, based on the Euler-Lotka equation, shows that density itself is irrelevant, but that the relative effect of density on adult and juvenile features is crucial. For instance, increasing population will select for a smaller body size if the density affects mainly juvenile growth and/or survival. In this case, density shoud indeed favour large body sizes. The theory appears nevertheless inconsistent, since a probable consequence of increasing body size will be a decrease in the carrying capacity

Extra-pair paternity, testes size and testosterone level in relation to colour polymorphism in the barn owl Tyto alba

In many bird populations, individuals display one of several genetically inherited colour morphs. Colour polymorphism can be maintained by several mechanisms one of which being frequency-dependent selection with colour morphs signalling alternative mating strategies. One morph may be dominant and territorial, and another one adopt a sneaky behaviour to gain access to fertile females. We tested this hypothesis in the barn owl Tyto alba in which coloration varies from reddish-brown to white. This trait is heritable and neither sensitive to the environment in which individuals live nor to body condition. In Switzerland, reddish-brown males were observed to feed their brood at a higher rate and to produce more offspring than white males. This observation lead us to hypothesize that white males may equalise fitness by investing more effort in extra-pair copulations. This hypothesis predicts that lighter Coloured males produce more extra-pair young, have larger testes and higher levels of circulating testosterone. However, our results are not consistent with these three predictions. First, paternity analyses of 54 broods with a total of 211 offspring revealed that only one young was not sired by the male that was feeding it. Second, testes size was not correlated with male plumage coloration suggesting that white males are not sexually more active. Finally, in nestlings at the time of feather growth testosterone level was not related to plumage coloration suggesting that this androgen is not required for the expression of this plumage trait. Our study therefore indicates that in the barn owl colour polymorphism plays no role in the probability of producing extra-pair young.

The ontogeny of sexual size dimorphism of a moth: when do males and females grow apart?

Sexual dimorphism in body size (sexual size dimorphism) is common in many species. The sources of selection that generate the independent evolution of adult male and female size have been investigated extensively by evolutionary biologists, but how and when females and males grow apart during ontogeny is poorly understood. Here we use the hawkmoth, Manduca sexta, to examine when sexual size dimorphism arises by measuring body mass every day during development. We further investigated whether environmental variables influence the ontogeny of sexual size dimorphism by raising moths on three different diet qualities (poor, medium and high). We found that size dimorphism arose during early larval development on the highest quality food treatment but it arose late in larval development when raised on the medium quality food. This female-biased dimorphism (females larger) increased substantially from the pupal-to-adult stage in both treatments, a pattern that appears to be common in Lepidopterans. Although dimorphism appeared in a few stages when individuals were raised on the poorest quality diet, it did not persist such that male and female adults were the same size. This demonstrates that the environmental conditions that insects are raised in can affect the growth trajectories of males and females differently and thus when dimorphism arises or disappears during development. We conclude that the development of sexual size dimorphism in M. sexta occurs during larval development and continues to accumulate during the pupal/adult stages, and that environmental variables such as diet quality can influence patterns of dimorphism in adults.

The red island and the seven dwarfs: body size reduction in Cheirogaleidae

AimSmall body size in Madagascar's dwarf and mouse lemurs (Cheirogaleidae) is generally viewed as primitive. We investigated the evolution of body size in this family and in its sister-taxon, the Lepilemuridae, from phylogenetic, ontogenetic and adaptive perspectives. LocationMadagascar. MethodsWe used a phylogenetic method to reconstruct the evolution of body size in lemurs, and allometric regression models of gestation periods and static and growth allometries in Cheirogaleidae and Lepilemuridae to test the hypothesis that dwarfing occurred as a result of truncated ontogeny (progenesis). We also examined adaptive hypotheses relating body size to environmental variability, life history, seasonality of reproduction, hypothermy (use of torpor), and a diet rich in plant exudates. ResultsOur results indicated that cheirogaleids experienced at least four independent events of body size reduction from an ancestor as large as living Lepilemuridae, by means of progenesis. Our interpretation is supported by the paedomorphic appearance and parallel ontogenetic trajectories of the dwarf taxa, as well as their very short gestation periods and increased fecundity. Lepilemur species that occupy more predictable environments are significantly larger than those occupying unpredictable habitats. Main conclusionsCheirogaleidae appear to be paedomorphic dwarfs, a consequence of progenesis, probably as an adaptation to high environmental unpredictability. Although the capacity to use hypothermy is related to small body size, this advantage is unlikely to have driven dwarfing in cheirogaleids. We propose that gummmivory/exudativory co-evolved with body size reduction in this clade, probably from a folivorous ancestor. Their small size is derived, and their suitability as models for the ancestral primate' is therefore dubious.