Decreased body mass index is associated with impaired survival in lung cancer patients with brain metastases: A retrospective analysis of 624 patients.

Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50-24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 [64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed. Histology was non-small cell lung cancer in 417/622 (66.8%), small cell lung cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%) patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight and 39/624 (6.3%) were underweight. Underweight patients had shorter median overall survival (3 months) compared to patients with normal BMI (7 months) and overweight (8 months; p < .001; log rank test). At multivariate analysis, higher GPA class (HR 1.430; 95% cumulative incidence, CI 1.279-1.598; p < .001; Cox regression model), SCLC histology (HR 1.310; 95% CI 1.101-1.558) and presence of underweight (HR 1.845; 95% CI 1.317-2.585; p = .014; Cox regression model) were independent prognostic factors. Underweight at diagnosis of BM in lung cancer is associated with an unfavourable prognosis.

Fish length exclusively determines sexual maturation in the European whitefish Coregonus lavaretus species complex.

The probability that a fish matures at a certain age and length (the so-called probabilistic maturation reaction norm, PMRN) was analysed for a European whitefish Coregonus lavaretus species complex population living in the Austrian pre-alpine Lake Irrsee. Fish length was found to be the only relevant determinant of maturation probability, and females matured at slightly smaller sizes than males.

Hybridization and speciation.

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.

A generalized functional response for predators that switch between multiple prey species.

We develop a theory for the food intake of a predator that can switch between multiple prey species. The theory addresses empirical observations of prey switching and is based on the behavioural assumption that a predator tends to continue feeding on prey that are similar to the prey it has consumed last, in terms of, e.g., their morphology, defences, location, habitat choice, or behaviour. From a predator's dietary history and the assumed similarity relationship among prey species, we derive a general closed-form multi-species functional response for describing predators switching between multiple prey species. Our theory includes the Holling type II functional response as a special case and makes consistent predictions when populations of equivalent prey are aggregated or split. An analysis of the derived functional response enables us to highlight the following five main findings. (1) Prey switching leads to an approximate power-law relationship between ratios of prey abundance and prey intake, consistent with experimental data. (2) In agreement with empirical observations, the theory predicts an upper limit of 2 for the exponent of such power laws. (3) Our theory predicts deviations from power-law switching at very low and very high prey-abundance ratios. (4) The theory can predict the diet composition of a predator feeding on multiple prey species from diet observations for predators feeding only on pairs of prey species. (5) Predators foraging on more prey species will show less pronounced prey switching than predators foraging on fewer prey species, thus providing a natural explanation for the known difficulties of observing prey switching in the field.

A systematic overview of harvesting-induced maturation evolution in predator-prey systems with three different life-history tradeoffs.

There are concerns that anthropogenic harvesting may cause phenotypic adaptive changes in exploited wild populations, in particular maturation at a smaller size and younger age. In this paper, we study the evolutionarily stable size at maturation of prey subjected to size-selective harvesting in a simple predator-prey model, taking into account three recognized life-history costs of early maturation, namely reduced fecundity, reduced growth, and increased mortality. Our analysis shows that harvesting large individuals favors maturation at smaller size compared to the unharvested system, independent of life-history tradeoff and the predator's prey-size preference. In general, however, the evolutionarily stable maturation size can either increase or decrease relative to the unharvested system, depending on the harvesting regime, the life-history tradeoff, and the predator's preferred size of prey. Furthermore, we examine how the predator population size changes in response to adaptive change in size at maturation of the prey. Surprisingly, in some situations, we find that the evolutionarily stable maturation size under harvesting is associated with an increased predator population size. This occurs, in particular, when early maturation trades off with growth rate. In total, we determine the evolutionarily stable size at maturation and associated predator population size for a total of forty-five different combinations of tradeoff, harvest regime, and predated size class.

Harvest-induced maturation evolution under different life-history trade-offs and harvesting regimes.

The potential of harvesting to induce adaptive changes in exploited populations is now increasingly recognized. While early studies predicted that elevated mortalities among larger individuals select for reduced maturation size, recent theoretical studies have shown conditions under which other, more complex evolutionary responses to size-selective mortality are expected. These new predictions are based on the assumption that, owing to the trade-off between growth and reproduction, early maturation implies reduced growth. Here we extend these findings by analyzing a model of a harvested size-structured population in continuous time, and by systematically exploring maturation evolution under all three traditionally acknowledged costs of early maturation: reduced fecundity, reduced growth, and/or increased natural mortality. We further extend this analysis to the two main types of harvest selectivity, with an individual's chance of getting harvested depending on its size and/or maturity stage. Surprisingly, we find that harvesting mature individuals not only favors late maturation when the costs of early maturation are low, but promotes early maturation when the costs of early maturation are high. To our knowledge, this study therefore is the first to show that harvesting mature individuals can induce early maturation.

Long-range correlations improve understanding of the influence of network structure on contact dynamics.

Models of infectious diseases are characterized by a phase transition between extinction and persistence. A challenge in contemporary epidemiology is to understand how the geometry of a host's interaction network influences disease dynamics close to the critical point of such a transition. Here we address this challenge with the help of moment closures. Traditional moment closures, however, do not provide satisfactory predictions close to such critical points. We therefore introduce a new method for incorporating longer-range correlations into existing closures. Our method is technically simple, remains computationally tractable and significantly improves the approximation's performance. Our extended closures thus provide an innovative tool for quantifying the influence of interaction networks on spatially or socially structured disease dynamics. In particular, we examine the effects of a network's clustering coefficient, as well as of new geometrical measures, such as a network's square clustering coefficients. We compare the relative performance of different closures from the literature, with or without our long-range extension. In this way, we demonstrate that the normalized version of the Bethe approximation-extended to incorporate long-range correlations according to our method-is an especially good candidate for studying influences of network structure. Our numerical results highlight the importance of the clustering coefficient and the square clustering coefficient for predicting disease dynamics at low and intermediate values of transmission rate, and demonstrate the significance of path redundancy for disease persistence.

Evolutionary dynamics of altruism and cheating among social amoebas.

Dictyostelium discoideum is a eukaryotic amoeba, which, when starvation is imminent, aggregates to form fruiting bodies consisting of a stalk of reproductively dead cells that supports spores. Because different clones may be involved in such aggregations, cheater strategies may emerge that allocate a smaller fraction of cells to stalk formation, thus gaining a reproductive advantage. In this paper, we model the evolutionary dynamics of allocation strategies in Dictyostelium under the realistic assumption that the number of clones involved in aggregations follows a random distribution. By determining the full course of evolutionary dynamics, we show that evolutionary branching in allocation strategies may occur, resulting in dimorphic populations that produce stalkless and stalked fruiting bodies. We also demonstrate that such dimorphisms are more likely to emerge when the variation in the number of clones involved in aggregations is large.

Can the evolution of plant defense lead to plant-herbivore mutualism?

Moderate rates of herbivory can enhance primary production. This hypothesis has led to a controversy as to whether such positive effects can result in mutualistic interactions between plants and herbivores. We present a model for the ecology and evolution of plant-herbivore systems to address this question. In this model, herbivores have a positive indirect effect on plants through recycling of a limiting nutrient. Plants can evolve but are constrained by a trade-off between growth and antiherbivore defense. Although evolution generally does not lead to optimal plant performance, our evolutionary analysis shows that, under certain conditions, the plant-herbivore interaction can be considered mutualistic. This requires in particular that herbivores efficiently recycle nutrients and that plant reproduction be positively correlated with primary production. We emphasize that two different definitions of mutualism need to be distinguished. A first ecological definition of mutualism is based on the short-term response of plants to herbivore removal, whereas a second evolutionary definition rests on the long-term response of plants to herbivore removal, allowing plants to adapt to the absence of herbivores. The conditions for an evolutionary mutualism are more stringent than those for an ecological mutualism. A particularly counterintuitive result is that higher herbivore recycling efficiency results both in increased plant benefits and in the evolution of increased plant defense. Thus, antagonistic evolution occurs within a mutualistic interaction.

On the origin of species by sympatric speciation.

Understanding speciation is a fundamental biological problem. It is believed that many species originated through allopatric divergence, where new species arise from geographically isolated populations of the same ancestral species. In contrast, the possibility of sympatric speciation (in which new species arise without geographical isolation) has often been dismissed, partly because of theoretical difficulties. Most previous models analysing sympatric speciation concentrated on particular aspects of the problem while neglecting others. Here we present a model that integrates a novel combination of different features and show that sympatric speciation is a likely outcome of competition for resources. We use multilocus genetics to describe sexual reproduction in an individual-based model, and we consider the evolution of assortative mating (where individuals mate preferentially with like individuals) depending either on an ecological character affecting resource use or on a selectively neutral marker trait. In both cases, evolution of assortative mating often leads to reproductive isolation between ecologically diverging subpopulations. When assortative mating depends on a marker trait, and is therefore not directly linked to resource competition, speciation occurs when genetic drift breaks the linkage equilibrium between the marker and the ecological trait. Our theory conforms well with mounting empirical evidence for the sympatric origin of many species.

The dynamical theory of coevolution: a derivation from stochastic ecological processes.

In this paper we develop a dynamical theory of coevolution in ecological communities. The derivation explicitly accounts for the stochastic components of evolutionary change and is based on ecological processes at the level of the individual. We show that the coevolutionary dynamic can be envisaged as a directed random walk in the community's trait space. A quantitative description of this stochastic process in terms of a master equation is derived. By determining the first jump moment of this process we abstract the dynamic of the mean evolutionary path. To first order the resulting equation coincides with a dynamic that has frequently been assumed in evolutionary game theory. Apart from recovering this canonical equation we systematically establish the underlying assumptions. We provide higher order corrections and show that these can give rise to new, unexpected evolutionary effects including shifting evolutionary isoclines and evolutionary slowing down of mean paths as they approach evolutionary equilibria. Extensions of the derivation to more general ecological settings are discussed. In particular we allow for multi-trait coevolution and analyze coevolution under nonequilibrium population dynamics.

The evolution of phenotypic plasticity in spatially structured environments: implications of intraspecific competition, plasticity costs and environmental characteristics.

We model the evolution of reaction norms focusing on three aspects: frequency-dependent selection arising from resource competition, maintenance and production costs of phenotypic plasticity, and three characteristics of environmental heterogeneity (frequency of environments, their intrinsic carrying capacity and the sensitivity to phenotypic maladaptation in these environments). We show that (i) reaction norms evolve so as to trade adaptation for acquiring resources against cost avoidance; (ii) maintenance costs cause reaction norms to better adapt to frequent rather than to infrequent environments, whereas production costs do not; and (iii) evolved reaction norms confer better adaptation to environments with low rather than with high intrinsic carrying capacity. The two previous findings contradict earlier theoretical results and originate from two previously unexplored features that are included in our model. First, production costs of phenotypic plasticity are only incurred when a given phenotype is actually produced. Therefore, they are proportional to the frequency of environments, and these frequencies thus affect the selection pressure to avoid costs just as much as the selection pressure to improve adaptation. This prevents the frequency of environments from affecting the evolving reaction norm. Secondly, our model describes the evolution of plasticity for a phenotype determining an individual's capability to acquire resources, and thus its realized carrying capacity. When individuals are distributed randomly across environments, they cannot avoid experiencing environments with intrinsically low carrying capacity. As selection pressures arising from the need to improve adaptation are stronger under such extreme conditions than under mild ones, better adaptation to environments with low rather than with high intrinsic carrying capacity results.

[Antigenic composition of adenovirus hexons]. / Untersuchungen zur Antigenstruktur der Adenovirushexone.

Quantitative relations between the group-specific and the type-specific components of the hexons of adenovirus type 2 and 5 were studied by means of FITC-conjugated Fab-fragments of antibodies directed against type 2 and type 5 hexons. From the sedimentation constant of the complexes of hexons and Fab in the region of excess of Fab we conclude that there are at least 20 determinants on the hexon. Half of these are type-specific and the others are group-specific. Both components of the type 2 hexon consist of equal parts of carbodiimide sensitive and carbodiimide resistent determinants.

Evolutionary dynamics of predator-prey systems: an ecological perspective.

Evolution takes place in an ecological setting that typically involves interactions with other organisms. To describe such evolution, a structure is needed which incorporates the simultaneous evolution of interacting species. Here a formal framework for this purpose is suggested, extending from the microscopic interactions between individuals--the immediate cause of natural selection, through the mesoscopic population dynamics responsible for driving the replacement of one mutant phenotype by another, to the macroscopic process of phenotypic evolution arising from many such substitutions. The process of coevolution that results from this is illustrated in the context of predator-prey systems. With no more than qualitative information about the evolutionary dynamics, some basic properties of predator-prey coevolution become evident. More detailed understanding requires specification of an evolutionary dynamic; two models for this purpose are outlined, one from our own research on a stochastic process of mutation and selection and the other from quantitative genetics. Much of the interest in coevolution has been to characterize the properties of fixed points at which there is no further phenotypic evolution. Stability analysis of the fixed points of evolutionary dynamical systems is reviewed and leads to conclusions about the asymptotic states of evolution rather different from those of game-theoretic methods. These differences become especially important when evolution involves more than one species.

[Risk factors for capsular rupture and vitreous loss in extracapsular cataract extraction. The Erlangen Ophthalmology Group]. / Risikofaktoren für Kapselruptur und Glaskörperverlust bei extrakapsulärer Kataraktextraktion. Erlanger Augenblätter-Gruppe.

A prospective study of preoperative risk factors in extracapsular cataract surgery was undertaken. The study included 2042 planned extracapsular cataract extractions in 1772 patients performed by 12 surgeons between February, 1986 and June, 1988. The possible risk factors to be analysed included sex, age, right or left eye, axial length, pseudoexfoliation syndrome, preceding blunt ocular trauma, diabetes mellitus and systemic hypertension. Capsular breaks occurred in 2.9% and vitreous loss in 1.9% of our patients. A significant increase in the frequency of capsular breaks was observed for patients under the age of 41 and for patients with diabetes mellitus, vitreous loss being observed significantly more frequently in eyes with pseudoexfoliation syndrome. A slight but insignificant increase in capsular breaks was observed for male patients, left eyes, eyes smaller than 22 mm, pseudoexfoliation syndrome and systemic hypertension. Advanced age, myopia and previous blunt trauma were not found to be significant risk factors for capsular breaks or vitreous loss. We recommend careful preoperative patient examination to identify preoperative risk factors and possibly avoid intraoperative complications.

Evolutionary cycling in predator-prey interactions: population dynamics and the red queen.

This paper describes the coevolution of phenotypes in a community comprising a population of predators and of prey. It is shown that evolutionary cycling is a likely outcome of the process. The dynamical systems on which this description is based are constructed from microscopic stochastic birth and death events, together with a process of random mutation. Births and deaths are caused in part by phenotype-dependent interactions between predator and prey individuals and therefore generate natural selection. Three outcomes of evolution are demonstrated. A community may evolve to a state at which the predator becomes extinct, or to one at which the species coexist with constant phenotypic values, or the species may coexist with cyclic changes in phenotypic values. The last outcome corresponds to a Red Queen dynamic, in which the selection pressures arising from the predator-prey interaction cause the species to evolve without ever reaching an equilibrium phenotypic state. The Red Queen dynamic requires an intermediate harvesting efficiency of the prey by the predator and sufficiently high evolutionary rate constant of the prey, and is robust when the model is made stochastic and phenotypically polymorphic. A cyclic outcome lies outside the contemporary focus on evolutionary equilibria, and argues for an extension to a dynamical framework for describing the asymptotic states of evolution.

[Antithrombin V--a rare concomitant symptom in plasmacytoma and autoimmune diseases]. / Antithrombin V--ein seltenes Begleitsymptom bei Plasmozytom und Autoimmunerkrankungen.

Antithrombin V as a pathological inhibitor of coagulation may occur in some rare cases as an accompanying symptom of various basic diseases. In the course of two years, antithrombin V could be identified in 8 patients, with plasmocytoma, lupus erythematodes visceralis, glomerulonephritis or colitis ulcerosa existing as basic diseases. Clinical findings in patients and those gained in analyzing coagulation, procedures of laboratory diagnostics for determining characteristic properties of antithrombin V as well as the therapeutic way of influencing the activity of antithrombin V are represented.

Evolution of dispersal in metapopulations with local density dependence and demographic stochasticity.

In this paper, we predict the outcome of dispersal evolution in metapopulations based on the following assumptions: (i) population dynamics within patches are density-regulated by realistic growth functions; (ii) demographic stochasticity resulting from finite population sizes within patches is accounted for; and (iii) the transition of individuals between patches is explicitly modelled by a disperser pool. We show, first, that evolutionarily stable dispersal rates do not necessarily increase with rates for the local extinction of populations due to external disturbances in habitable patches. Second, we describe how demographic stochasticity affects the evolution of dispersal rates: evolutionarily stable dispersal rates remain high even when disturbance-related rates of local extinction are low, and a variety of qualitatively different responses of adapted dispersal rates to varied levels of disturbance become possible. This paper shows, for the first time, that evolution of dispersal rates may give rise to monotonically increasing or decreasing responses, as well as to intermediate maxima or minima.

Laser-assisted cryopreservation of single human spermatozoa in cell-free zona pellucida.

Improved procedure for efficient cryopreservation of single human spermatozoa in cell-free human zona pellucida is reported. We used a diode laser system for efficient and precise creation of a single hole into the zona pellucida of a degenerated or immature human oocyte. This allowed the extraction of the cytoplasm using a micropipette with a diameter of 10-15 microns. Through the same opening, human spermatozoa were inserted into the empty zona. We used motile and laser immobilized spermatozoa. Immobilized sperm were obtained by a single laser irradiation delivered in the vicinity of the sperm tail prior to insertion. This new immobilization procedure was shown to have no deleterious effect on membrane integrity and sperm viability. Following sperm transfer into the zona, the laser-drilled hole was closed with an oil droplet which was expelled from the micropipette during withdrawal to avoid loss of spermatozoa. This facilitated detection of the otherwise translucent zona during the cryopreservation procedure. After thawing, all cryopreserved zonae (20/20) could be successfully retrieved. Spermatozoa were recovered from the zona pellucida through the hole used for insertion. The rate of sperm recovery for initially motile spermatozoa was 80% vs. 92% for laser immobilized spermatozoa. Sperm viability was 81% and 84%, respectively, detected by a Hoechst stain. This technique makes cryopreservation of single human spermatozoa easy and feasible and appears beneficial for couples with severe male infertility and for those facing repeated surgical sperm extraction.