Fitness, inclusive fitness, and optimization

Individual-as-maximizing agent analogies result in a simple understanding of the functioning of the biological world. Identifying the conditions under which individuals can be regarded as fitness maximizing agents is thus of considerable interest to biologists. Here, we compare different concepts of fitness maximization, and discuss within a single framework the relationship between Hamilton's (J Theor Biol 7: 1-16, 1964) model of social interactions, Grafen's (J Evol Biol 20: 1243-1254, 2007a) formal Darwinism project, and the idea of evolutionary stable strategies. We distinguish cases where phenotypic effects are additive separable or not, the latter not being covered by Grafen's analysis. In both cases it is possible to define a maximand, in the form of an objective function phi(z), whose argument is the phenotype of an individual and whose derivative is proportional to Hamilton's inclusive fitness effect. However, this maximand can be identified with the expression for fecundity or fitness only in the case of additive separable phenotypic effects, making individual-as-maximizing agent analogies unattractive (although formally correct) under general situations of social interactions. We also feel that there is an inconsistency in Grafen's characterization of the solution of his maximization program by use of inclusive fitness arguments. His results are in conflict with those on evolutionary stable strategies obtained by applying inclusive fitness theory, and can be repaired only by changing the definition of the problem.

Validation of the Addiction Severity Index in French-speaking alcoholic patients.

OBJECTIVE: Evaluation of a French translation of the Addiction Severity Index (ASI) in 100 (78 male) alcoholic patients. METHOD: Validity of the instrument was assessed by measuring test-retest and interrater reliability, internal consistency and convergence and discrimination between items and scales. Concurrent validity was assessed by comparing the scores from the ASI with those obtained from three other clinimetric instruments. RESULTS: Test-retest reliability of ASI scores (after a 10-day interval) was good (r = 0.63 to r = 0.95). Interrater reliability was evaluated using six video recordings of patient interviews. Severity ratings assigned by six rates were significantly different (p < .05), but 72% of the ratings assigned by those who viewed the videos were within two points of the interviewer's severity ratings. Cronbach alpha coefficient of internal consistency varied from 0.58 to 0.81 across scales. The average item-to-scale convergent validity (r value) was 0.49 (range 0.0 to 0.84) for composite scores and 0.35 (range 0.00 to 0.68) for severity ratings, whereas discriminant validity was 0.11 on average (range-0.19 to 0.46) for composite scores and 0.12 (range-0.20 to 0.52) for severity ratings. Finally, concurrent validity with the following instruments was assessed: Severity of Alcoholism Dependence Questionnaire (40% shared variance with ASI alcohol scale), Michigan Alcoholism Screening Test (2% shared variance with ASI alcohol scale) and Hamilton Depression Rating Scale (31% shared variance with ASI psychiatric scale). CONCLUSIONS: The Addiction Severity Index covers a large scope of problems encountered among alcoholics and quantifies need for treatment. This French version presents acceptable criteria of reliability and validity.

Little effect of seasonal constraints on population genetic structure in eusocial paper wasps.

Climate has long been suggested to affect population genetic structures of eusocial insect societies. For instance, Hamilton [Journal of Theoretical Biology7 (1964) 17] discusses whether temperate and tropical eusocial insects may show differences in population-level genetic structure and viscosity, and how this might relate to differences in the degree of synchrony in their life cycles or modes of nest founding. Despite the importance of Hamilton's 1964 papers, this specific idea has not been tested in actual populations of wasps, probably due to the paucity of studies on tropical species. Here, we compare colony and population genetic structures in two species of primitively eusocial paper wasps with contrasting ecologies: the tropical species Polistes canadensis and the temperate species P. dominulus. Our results provide important clarifications of Hamilton's discussion. Specifically, we show that the genetic structures of the temperate and tropical species were very similar, indicating that seasonality does not greatly affect population viscosity or inbreeding. For both species, the high genetic differentiation between nests suggests strong selection at the nest level to live with relatives, whereas low population viscosity and low genetic differentiation between nest aggregations might reflect balancing selection to disperse, avoiding competition with relatives. Overall, our study suggests no prevalence of seasonal constraints of the life cycle in affecting the population genetic structure of eusocial paper wasps. These conclusions are likely to apply also to other primitively eusocial insects, such as halictine bees. They also highlight how selection for a kin structure that promotes altruism can override potential effects of ecology in eusocial insects.

The automatic selection of ventilation parameters during the initial phase of mechanical ventilation.

OBJECTIVE: To test a method that allows automatic set-up of the ventilator controls at the onset of ventilation. DESIGN: Prospective randomized crossover study. SETTING: ICUs in one adult and one children's hospital in Switzerland. PATIENTS: Thirty intubated stable, critically ill patients (20 adults and 10 children). INTERVENTIONS: The patients were ventilated during two 20-min periods using a modified Hamilton AMADEUS ventilator. During the control period the ventilator settings were chosen immediately prior to the study. During the other period individual settings were automatically determined by the ventilatior (AutoInit). MEASUREMENTS AND RESULTS: Pressure, flow, and instantaneous CO2 concentration were measured at the airway opening. From these measurements, series dead space (V(DS)), expiratory time constant (RC), tidal volume (VT, total respiratory frequency (f(tot), minute ventilation (MV), and maximal and mean airway pressure (Paw, max and Paw, mean) were calculated. Arterial blood gases were analyzed at the end of each period. Paw, max was significantly less with the AutoInit ventilator settings while f(tot) was significantly greater (P < 0.05). The other values were not statistically significant. CONCLUSIONS: The AutoInit ventilator settings, which were automatically derived, were acceptable for all patients for a period of 20 min and were not found to be inferior to the control ventilator settings. This makes the AutoInit method potentially useful as an automatic start-up procedure for mechanical ventilation.

Essential role of platelet activation via protease activated receptor 4 in tissue factor-initiated inflammation.

INTRODUCTION: Tissue factor (TF) activation of the coagulation proteases enhances inflammation in animal models of arthritis and endotoxemia, but the mechanism of this effect is not yet fully understood - in particular, whether this is primarily due to fibrin formation or through activation of protease activated receptors (PARs). METHODS: We induced extravascular inflammation by injection of recombinant soluble murine TF (sTF1-219) in the hind paw. The effects of thrombin inhibition, fibrinogen and platelet depletion were evaluated, as well as the effects of PAR deficiency using knockout mice deficient for each of the PARs. RESULTS: Injection of soluble TF provoked a rapid onset of paw swelling. Inflammation was confirmed histologically and by increased serum IL-6 levels. Inflammation was significantly reduced by depletion of fibrinogen (P < 0.05) or platelets (P = 0.015), and by treatment with hirudin (P = 0.04) or an inhibitor of activated factor VII (P < 0.001) compared with controls. PAR-4-deficient mice exhibited significantly reduced paw swelling (P = 0.003). In contrast, a deficiency in either PAR-1, PAR-2 or PAR-3 did not affect the inflammatory response to soluble TF injection. CONCLUSION: Our results show that soluble TF induces acute inflammation through a thrombin-dependent pathway and both fibrin deposition and platelet activation are essential steps in this process. The activation of PAR-4 on platelets is crucial and the other PARs do not play a major role in soluble TF-induced inflammation.

Morphostructural analysis of an alpine debris flows catchment: implication for debris supply

Rock slope instabilities are implicitly linked to the supply of sediment and debris recharging channels prone to debris flow. Hence, the incorporation of bedrock structure and terrain morphology can be relevant in the analysis of sediment budget and debris flow hazard assessment. Here, the mode of debris production of the Manival catchment (northern French Alps) is documented by the study of its morphostructural aspects extracted from high resolution DEM. Terrain implication in the process of debris supply is evaluated by: a) A systematic classification of the major morphological units based on the slope gradient that enables a spatial analysis of zones of debris production and deposition. b) A detailed structural analysis performed on DEM in order to identify potential unstable slopes. c) An analysis of the gullies orientation that informs in term of structural control of the sources zones. d) Localisation of high density joints sets that document about whether sources of continuous debris production are controlled by the structural setting of the catchment. These DEM-based indicators can be used as proxies for assessing the influences of the current topography and enable to quantify a degree of susceptibility to mass wasting and hillslope erosion activity. This present contribution suggests some directions for characterizing sediment flux dynamic in small alpine catchment.

The genetical theory of social behaviour.

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1-16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments.

Deposits of transforming growth factor-beta-induced protein in granular corneal dystrophy type II after LASIK.

PURPOSE: To analyze components of the deposits in the corneal flap interface of granular corneal dystrophy type II (GCD II) patients after laser in situ keratomileusis (LASIK). METHODS: Four corneal GCD II specimens displaying disease exacerbation after LASIK were analyzed. Three of these specimens included the recipient corneal button after penetrating keratoplasty or deep lamellar keratoplasty for advanced GCD II after LASIK. The fourth specimen, a similar case of GCD II after LASIK, included the amputated corneal flap. Specimens were processed for histopathologic and immunohistochemical analyses. RESULTS: Corneal stromal deposits in the LASIK flaps of all specimens were stained with 3 anti-transforming growth factor-beta-induced protein (TGFBIp) antibodies. The deposits displayed bright red color staining with Masson trichrome; however, negative staining was seen with Congo red, suggesting that hyaline is the main component localizing to the TGFBIp deposits rather than amyloid. CONCLUSIONS: Amorphous granular material deposited along the interface of the LASIK flap in GCD II corneas is composed mainly of hyaline deposits.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2010-30 September 2010

This article documents the addition of 229 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acacia auriculiformis x Acacia mangium hybrid, Alabama argillacea, Anoplopoma fimbria, Aplochiton zebra, Brevicoryne brassicae, Bruguiera gymnorhiza, Bucorvus leadbeateri, Delphacodes detecta, Tumidagena minuta, Dictyostelium giganteum, Echinogammarus berilloni, Epimedium sagittatum, Fraxinus excelsior, Labeo chrysophekadion, Oncorhynchus clarki lewisi, Paratrechina longicornis, Phaeocystis antarctica, Pinus roxburghii and Potamilus capax. These loci were cross-tested on the following species: Acacia peregrinalis, Acacia crassicarpa, Bruguiera cylindrica, Delphacodes detecta, Tumidagena minuta, Dictyostelium macrocephalum, Dictyostelium discoideum, Dictyostelium purpureum, Dictyostelium mucoroides, Dictyostelium rosarium, Polysphondylium pallidum, Epimedium brevicornum, Epimedium koreanum, Epimedium pubescens, Epimedium wushanese and Fraxinus angustifolia.

A community survey of sun exposure, sunburn and sun protection.

AIM: To describe outdoor activities, sun protection behaviours and the experience of sunburn in a sample of New Zealanders during summer weekends of 1994. METHODS: 1243 respondents to a telephone survey provided information regarding their outdoor activities for the 5 hour period around midday of the previous Saturday and Sunday. The sample was drawn from those aged 15 to 65 years in the five centres of Auckland, Hamilton, Wellington, Christchurch and Dunedin. Respondents provided information on sun exposure, sunburn, sun protection and beliefs about tanning, as well as background demographic information, skin type and previous experience of sunburn. RESULTS: 12% of the sample (or 17% of all those outdoors) reported being sunburned on the preceding weekend, and those sunburned tended to be men, and to be under age 35 years. The face, neck and limbs were the areas most frequently reported as burned. Sporting activities and beach or water activities were associated with the highest number of episodes of burning. Overall 38% of those outside reported wearing a hat and 32% reported the use of a sunscreen. Positive attitudes to tanning were quite common and probably present the main target for change in the community. CONCLUSION: On any sunny weekend in summer about three-quarters of adult New Zealanders will be out in the sun for relatively long periods of time, and many will get sunburned. The reduction of such harmful sun exposures remains an important public health goal.

The stationary distribution of a continuously varying strategy in a class-structured population under mutation-selection-drift balance.

Many traits and/or strategies expressed by organisms are quantitative phenotypes. Because populations are of finite size and genomes are subject to mutations, these continuously varying phenotypes are under the joint pressure of mutation, natural selection and random genetic drift. This article derives the stationary distribution for such a phenotype under a mutation-selection-drift balance in a class-structured population allowing for demographically varying class sizes and/or changing environmental conditions. The salient feature of the stationary distribution is that it can be entirely characterized in terms of the average size of the gene pool and Hamilton's inclusive fitness effect. The exploration of the phenotypic space varies exponentially with the cumulative inclusive fitness effect over state space, which determines an adaptive landscape. The peaks of the landscapes are those phenotypes that are candidate evolutionary stable strategies and can be determined by standard phenotypic selection gradient methods (e.g. evolutionary game theory, kin selection theory, adaptive dynamics). The curvature of the stationary distribution provides a measure of the stability by convergence of candidate evolutionary stable strategies, and it is evaluated explicitly for two biological scenarios: first, a coordination game, which illustrates that, for a multipeaked adaptive landscape, stochastically stable strategies can be singled out by letting the size of the gene pool grow large; second, a sex-allocation game for diploids and haplo-diploids, which suggests that the equilibrium sex ratio follows a Beta distribution with parameters depending on the features of the genetic system.

An index of 5-HT synthesis changes during early antidepressant treatment: α-[11C]methyl-l-tryptophan PET study

The antidepressant selective serotonin transporter inhibitors (SSRIs) are clinically active after a delay of several weeks. Indeed, the rapid increase of serotonin (5-HT) caused by SSRIs, stimulates the 5-HT1A autoreceptors, which exert a negative feedback on the 5-HT neurotransmission. Only when autoreceptors are desensitized, can SSRIs exert their therapeutic activity. The 5-HT1A receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback. Using the a-[11C]methyl-L-tryptophan/positron emission tomography (PET), the goal of the present double-blind, randomized study was to compare the changes in a-[11C]methyl-L-tryptophan trapping, an index of serotonin synthesis, in patients suffering from unipolar depression treated with the SSRI citalopram (20 mg/day) plus placebo versus patients treated with citalopram plus pindol (7.5 mg/day). PET and Hamilton depression rating scale (HDRS-17) were performed at baseline, and after 10 and 24 days of antidepressant treatment. Results show that the combination citalopram plus pindol, compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex (BA 9). This research is the first human PET study demonstrating that, after 24 days, the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex, an area associated to depressive symptoms.

Defensive flexibility and its relation to symptom severity, depression, and anxiety.

Numerous studies have examined which individual defense mechanisms are related with mental health, and which are linked with psychopathology. However, the idea that a flexible use of defensive mechanisms is related to psychological wellbeing remained a clinical assumption, which this study sought to test empirically. A total of 62 (N = 62) outpatients participated in the study and were assessed with the Symptom Checklist-90R and the Social Adjustment Self-rated Scale. A subsample of 40 participants was further assessed using the Hamilton Depression (HAMD-21) and Anxiety scales (HAMA-21). The first therapy session of all participants was transcribed and rated using the Defense Mechanisms Ratings Scales (), and the Overall Defensive Functioning (ODF) score, which indicates the maturity of one's defensive functioning, was computed. An indicator of flexible use of defenses was also calculated based on the Gini Concentration C measure. Results showed that defensive flexibility, but not ODF, could predict anxiety scores. Symptom severity was predicted by both ODF and defensive flexibility, although in directions opposite to our predictions. Results suggest that defensive flexibility captures another aspect of an individual's functioning not assessed by the ODF, and that it is a promising new way of documenting defensive functioning.

Multicenter Study on the Clinical Effectiveness, Pharmacokinetics, and Pharmacogenetics of Mirtazapine in Depression.

ABSTRACT: Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.