Subjective health assessments and active labor market participation of older men: evidence from a semiparametric binary choice model with nonadditive correlated individual-specific effects

We use panel data from the U. S. Health and Retirement Study, 1992-2002, to estimate the effect of self-assessed health limitations on the active labor market participation of older men. Self-assessments of health are likely to be endogenous to labor supply due to justification bias and individual-specific heterogeneity in subjective evaluations. We address both concerns. We propose a semiparametric binary choice procedure that incorporates nonadditive correlated individual-specific effects. Our estimation strategy identifies and estimates the average partial effects of health and functioning on labor market participation. The results indicate that poor health plays a major role in labor market exit decisions.

Individual vocal signatures in barn owl nestlings: does individual recognition have an adaptive role in sibling vocal competition?

To compete over limited parental resources, young animals communicate with their parents and siblings by producing honest vocal signals of need. Components of begging calls that are sensitive to food deprivation may honestly signal need, whereas other components may be associated with individual-specific attributes that do not change with time such as identity, sex, absolute age and hierarchy. In a sib-sib communication system where barn owl (Tyto alba) nestlings vocally negotiate priority access to food resources, we show that calls have individual signatures that are used by nestlings to recognize which siblings are motivated to compete, even if most vocalization features vary with hunger level. Nestlings were more identifiable when food-deprived than food-satiated, suggesting that vocal identity is emphasized when the benefit of winning a vocal contest is higher. In broods where siblings interact iteratively, we speculate that individual-specific signature permits siblings to verify that the most vocal individual in the absence of parents is the one that indeed perceived the food brought by parents. Individual recognition may also allow nestlings to associate identity with individual-specific characteristics such as position in the within-brood dominance hierarchy. Calls indeed revealed age hierarchy and to a lower extent sex and absolute age. Using a cross-fostering experimental design, we show that most acoustic features were related to the nest of origin (but not the nest of rearing), suggesting a genetic or an early developmental effect on the ontogeny of vocal signatures. To conclude, our study suggests that sibling competition has promoted the evolution of vocal behaviours that signal not only hunger level but also intrinsic individual characteristics such as identity, family, sex and age.

Nestling barn owls assess short-term variation in the amount of vocally competing siblings.

Assessing the amount of rivals is crucial to optimally adjust investment into a contest. If laboratory animals show numerical abilities, little is known about the ecological implications particularly in young animals. The two to nine barn owl (Tyto alba) siblings vocally compete for priority of access to food resources before parents actually deliver them. In dyads, the individual that vocalizes at the highest rate in the absence of parents deters its siblings from competing for next delivered prey. We tested the novel hypothesis that to optimally adjust vocal investment, barn owl nestlings assess how many of their siblings are currently competing. To singleton owlets, we broadcasted a fixed global number of calls emitted by one, two or four pre-recorded unfamiliar nestlings. We could thus distinguish the independent effect on singletons' vocal behavior of the global number of calls produced by a brood from the number of competitors that produced these calls. Overall, nestlings retreated more from vocal contest when facing more competitors. However, in front of one highly motivated competitor, nestlings refrained from vocalizing to a larger extent than when competing against more but less motivated individuals. Therefore, young animals assess variation in the number of currently competing siblings based on individual-specific vocal cues.

Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype.

PURPOSE: To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). PATIENTS AND METHODS: Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. RESULTS: Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy -7 (n = 63; 4-year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3;3]) associated with very poor outcome. CONCLUSION: MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% +/- 2%) and the highly unfavorable risk MK-positive category (4-year OS, 4% +/- 1%).

Linking brain structure and activation in the temporoparietal junction to explain the neurobiology of human altruism

Human altruism shaped our evolutionary history and pervades social and political life. There are, however, enormous individual differences in altruism. Some people are almost completely selfish, while others display strong altruism, and the factors behind this heterogeneity are only poorly understood. We examine the neuroanatomical basis of these differences with voxel-based morphometry and show that gray matter (GM) volume in the right temporoparietal junction (TPJ) is strongly associated with both individuals' altruism and the individual-specific conditions under which this brain region is recruited during altruistic decision making. Thus, individual differences in GM volume in TPJ not only translate into individual differences in the general propensity to behave altruistically, but they also create a link between brain structure and brain function by indicating the conditions under which individuals are likely to recruit this region when they face a conflict between altruistic and selfish acts.

Comprehensive Expression Analyses of Neural Cell-Type-Specific miRNAs Identify New Determinants of the Specification and Maintenance of Neuronal Phenotypes.

MicroRNAs (miRNAs) have been shown to play important roles in both brain development and the regulation of adult neural cell functions. However, a systematic analysis of brain miRNA functions has been hindered by a lack of comprehensive information regarding the distribution of miRNAs in neuronal versus glial cells. To address this issue, we performed microarray analyses of miRNA expression in the four principal cell types of the CNS (neurons, astrocytes, oligodendrocytes, and microglia) using primary cultures from postnatal d 1 rat cortex. These analyses revealed that neural miRNA expression is highly cell-type specific, with 116 of the 351 miRNAs examined being differentially expressed fivefold or more across the four cell types. We also demonstrate that individual neuron-enriched or neuron-diminished RNAs had a significant impact on the specification of neuronal phenotype: overexpression of the neuron-enriched miRNAs miR-376a and miR-434 increased the differentiation of neural stem cells into neurons, whereas the opposite effect was observed for the glia-enriched miRNAs miR-223, miR-146a, miR-19, and miR-32. In addition, glia-enriched miRNAs were shown to inhibit aberrant glial expression of neuronal proteins and phenotypes, as exemplified by miR-146a, which inhibited neuroligin 1-dependent synaptogenesis. This study identifies new nervous system functions of specific miRNAs, reveals the global extent to which the brain may use differential miRNA expression to regulate neural cell-type-specific phenotypes, and provides an important data resource that defines the compartmentalization of brain miRNAs across different cell types.

Combined clonotyping and gene signatures of individual tumor-reactive CD8 T-cells define their functional relevance following peptide vaccination in melanoma patients

Novel cancer vaccines are capableto efficiently induce and boost humantumor antigen specific T-cells. However,the properties of these CD8T-cells are only partially characterized.For in depth investigation ofT-cells following Melan-A/MART-1peptide vaccination in melanoma patients,we conducted a detailed prospectivestudy at the single cell level.We first sorted individual human naiveand effector CD8 T-cells from peripheralblood by flow cytometry, andtested a modified RT-PCR protocolincluding a global amplification ofexpressed mRNAs to obtain sufficientcDNAfromsingle cells.We successfullydetected the expression ofseveral specific genes of interest evendown to 106-fold dilution (equivalentto 10-5 cell). We then analyzed tumor-specific effector memory (EM)CD8T-cell subpopulations ex vivo, assingle cells from vaccinated melanomapatients. To elucidate the hallmarksof effective immunity the genesignatures were defined by a panel ofgenes related to effector functions(e.g. IFN-, granzyme B, perforin),and individual clonotypes were identifiedaccording to the expression ofdistinct T-cell receptors (TCR). Usingthis novel single cell analysis approach,we observed that T-cell differentiationis clonotype dependent,with a progressive restriction in TCRBV clonotype diversity from EMCD28pos to EMCD28neg subsets. However,the effector function gene imprintingis clonotype-independent,but dependent on differentiation,since it correlates with the subset oforigin (EMCD28pos or EMCD28neg). We also conducted a detailedcomparative analysis after vaccinationwith natural vs. analog Melan-Apeptide. We found that the peptideused for vaccination determines thefunctional outcome of individualT-cell clonotypes, with native peptideinducing more potent effector functions.Yet, selective clonotypic expansionwith differentiation was preservedregardless of the peptide usedfor vaccination. In summary, the exvivo single cell RT-PCR approach ishighly sensitive and efficient, andrepresents a reliable and powerfultool to refine our current view of molecularprocesses taking place duringT-cell differentiation.

A general model to predict individual exposure to solar UV by using ambient irradiance data

Excessive exposure to solar ultraviolet (UV) is the main cause of skin cancer. Specific prevention should be further developed to target overexposed or highly vulnerable populations. A better characterisation of anatomical UV exposure patterns is however needed for specific prevention. To develop a regression model for predicting the UV exposure ratio (ER, ratio between the anatomical dose and the corresponding ground level dose) for each body site without requiring individual measurements. A 3D numeric model (SimUVEx) was used to compute ER for various body sites and postures. A multiple fractional polynomial regression analysis was performed to identify predictors of ER. The regression model used simulation data and its performance was tested on an independent data set. Two input variables were sufficient to explain ER: the cosine of the maximal daily solar zenith angle and the fraction of the sky visible from the body site. The regression model was in good agreement with the simulated data ER (R(2)=0.988). Relative errors up to +20% and -10% were found in daily doses predictions, whereas an average relative error of only 2.4% (-0.03% to 5.4%) was found in yearly dose predictions. The regression model predicts accurately ER and UV doses on the basis of readily available data such as global UV erythemal irradiance measured at ground surface stations or inferred from satellite information. It renders the development of exposure data on a wide temporal and geographical scale possible and opens broad perspectives for epidemiological studies and skin cancer prevention.

Endogenous steroid profiling in the athlete biological passport.

The Athlete Biological Passport (ABP) is an individual electronic document that collects data regarding a specific athlete that is useful in differentiating between natural physiologic variations of selected biomarkers and deviations caused by artificial manipulations. A subsidiary of the endocrine module of the ABP, that which here is called Athlete Steroidal Passport (ASP), collects data on markers of an altered metabolism of endogenous steroidal hormones measured in urine samples. The ASP aims to identify not only doping with anabolic-androgenic steroids, but also most indirect steroid doping strategies such as doping with estrogen receptor antagonists and aromatase inhibitors. Development of specific markers of steroid doping, use of the athlete's previous measurements to define individual limits, with the athlete becoming his or her own reference, the inclusion of heterogeneous factors such as the UDPglucuronosyltransferase B17 genotype of the athlete, the knowledge of potentially confounding effects such as heavy alcohol consumption, the development of an external quality control system to control analytical uncertainty, and finally the use of Bayesian inferential methods to evaluate the value of indirect evidence have made the ASP a valuable alternative to deter steroid doping in elite sports. The ASP can be used to target athletes for gas chromatography/combustion/ isotope ratio mass spectrometry (GC/C/IRMS) testing, to withdraw temporarily the athlete from competing when an abnormality has been detected, and ultimately to lead to an antidoping infraction if that abnormality cannot be explained by a medical condition. Although the ASP has been developed primarily to ensure fairness in elite sports, its application in endocrinology for clinical purposes is straightforward in an evidence-based medicine paradigm.

Differential species-specific ectoparasitic mite intensities in two intimately coexisting sibling bat species: resource-mediated host attractiveness or parasite specialization?

1. The mechanisms underlying host choice strategies by parasites remain poorly understood. We address two main questions: (i) do parasites prefer vulnerable or well-fed hosts, and (ii) to what extent is a parasite species specialized towards a given host species? 2. To answer these questions, we investigated, both in the field and in the lab, a host-parasite system comprising one ectoparasitic mite (Spinturnix myoti) and its major hosts, two sibling species of bats (Myotis myotis and M blythii), which coexist intimately in colonial nursery roosts. We exploited the close physical associations between host species in colonial roosts as well as naturally occurring annual variation in food abundance to investigate the relationships between parasite intensities and (i) host species and (ii) individual nutritional status. 3. Although horizontal transmission of parasites was facilitated by the intimate aggregation of bats within their colonial clusters, we found significant interspecific differences in degree of infestation throughout the 6 years of the study, with M. myotis always more heavily parasitized than M. blythii. This pattern was replicated in a laboratory experiment in which any species-specific resistance induced by exploitation of different trophic niches in nature was removed. 4. Within both host species, S. myoti showed a clear preference for individuals with higher nutritional status. In years with high resource abundance, both bat hosts harboured more parasites than in low-resource years, although the relative difference in parasite burden across species was maintained. This pattern of host choice was also replicated in the laboratory. When offered a choice, parasites always colonized better-fed individuals. 5. These results show first that host specialization in our study system occurred. Second, immediate parasite choice clearly operated towards the selection of hosts in good nutritional state.

Assessing ageing of individual T lymphocytes: mission impossible?

Effector T lymphocytes are the progeny of a limited number of antigen-specific precursor cells and it has been estimated that clonotypic human T cells may expand million fold on their way reaching high cell numbers that are sufficient for immune protection. Moreover, memory T cell responses are characterized by repetitive expansion of antigen-specific T cell clonotypes, and limitations in the proliferative capacity could lead to immune senescence. Because telomeres progressively shorten as a function of cell division, telomere length is a powerful indicator of the replicative in vivo history of human T lymphocytes. In this review, we summarize observations made over the last decade on telomere length dynamics of well-defined T cell populations derived from healthy donors and patients with infectious disease or cancer. We focus on T cell differentiation, T cell ageing, and natural and vaccine induced immune responses. We also discuss the scientific evidence for in vivo replicative senescence of antigen-specific T cells, and evaluate the available methods for measuring telomere lengths and telomerase activity, and their potential and limitations to increase our understanding of T cell physiology.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.

Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

BACKGROUND: Synthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen. METHODS: Individual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen. RESULTS: The combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing. CONCLUSIONS: The hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human. TRIAL REGISTRATION: ClinicalTrials.gov NCT01719133.

Oncology clinicians' defenses and adherence to communication skills training with simulated patients: an exploratory study.

The aim of this exploratory study was to assess the impact of clinicians' defense mechanisms-defined as self-protective psychological mechanisms triggered by the affective load of the encounter with the patient-on adherence to a communication skills training (CST). The population consisted of oncology clinicians (N = 31) who participated in a CST. An interview with simulated cancer patients was recorded prior and 6 months after CST. Defenses were measured before and after CST and correlated with a prototype of an ideally conducted interview based on the criteria of CST-teachers. Clinicians who used more adaptive defense mechanisms showed better adherence to communication skills after CST than clinicians with less adaptive defenses (F(1, 29) = 5.26, p = 0.03, d = 0.42). Improvement in communication skills after CST seems to depend on the initial levels of defenses of the clinician prior to CST. Implications for practice and training are discussed. Communication has been recognized as a central element of cancer care [1]. Ineffective communication may contribute to patients' confusion, uncertainty, and increased difficulty in asking questions, expressing feelings, and understanding information [2, 3], and may also contribute to clinicians' lack of job satisfaction and emotional burnout [4]. Therefore, communication skills trainings (CST) for oncology clinicians have been widely developed over the last decade. These trainings should increase the skills of clinicians to respond to the patient's needs, and enhance an adequate encounter with the patient with efficient exchange of information [5]. While CSTs show a great diversity with regard to their pedagogic approaches [6, 7], the main elements of CST consist of (1) role play between participants, (2) analysis of videotaped interviews with simulated patients, and (3) interactive case discussion provided by participants. As recently stated in a consensus paper [8], CSTs need to be taught in small groups (up to 10-12 participants) and have a minimal duration of at least 3 days in order to be effective. Several systematic reviews evaluated the impact of CST on clinicians' communication skills [9-11]. Effectiveness of CST can be assessed by two main approaches: participant-based and patient-based outcomes. Measures can be self-reported, but, according to Gysels et al. [10], behavioral assessment of patient-physician interviews [12] is the most objective and reliable method for measuring change after training. Based on 22 studies on participants' outcomes, Merckaert et al. [9] reported an increase of communication skills and participants' satisfaction with training and changes in attitudes and beliefs. The evaluation of CST remains a challenging task and variables mediating skills improvement remain unidentified. We recently thus conducted a study evaluating the impact of CST on clinicians' defenses by comparing the evolution of defenses of clinicians participating in CST with defenses of a control group without training [13]. Defenses are unconscious psychological processes which protect from anxiety or distress. Therefore, they contribute to the individual's adaptation to stress [14]. Perry refers to the term "defensive functioning" to indicate the degree of adaptation linked to the use of a range of specific defenses by an individual, ranging from low defensive functioning when he or she tends to use generally less adaptive defenses (such as projection, denial, or acting out) to high defensive functioning when he or she tends to use generally more adaptive defenses (such as altruism, intellectualization, or introspection) [15, 16]. Although several authors have addressed the emotional difficulties of oncology clinicians when facing patients and their need to preserve themselves [7, 17, 18], no research has yet been conducted on the defenses of clinicians. For example, repeated use of less adaptive defenses, such as denial, may allow the clinician to avoid or reduce distress, but it also diminishes his ability to respond to the patient's emotions, to identify and to respond adequately to his needs, and to foster the therapeutic alliance. Results of the above-mentioned study [13] showed two groups of clinicians: one with a higher defensive functioning and one with a lower defensive functioning prior to CST. After the training, a difference in defensive functioning between clinicians who participated in CST and clinicians of the control group was only showed for clinicians with a higher defensive functioning. Some clinicians may therefore be more responsive to CST than others. To further address this issue, the present study aimed to evaluate the relationship between the level of adherence to an "ideally conducted interview", as defined by the teachers of the CST, and the level of the clinician' defensive functioning. We hypothesized that, after CST, clinicians with a higher defensive functioning show a greater adherence to the "ideally conducted interview" than clinicians with a lower defensive functioning.

Monitoring of vaccine-specific gamma interferon induction in genital mucosa of mice by real-time reverse transcription-PCR.

Monitoring of T-cell responses in genital mucosa has remained a major challenge because of the absence of lymphoid aggregates and the low abundance of T cells. Here we have adapted to genital tissue a sensitive real-time reverse transcription-PCR (TaqMan) method to measure induction of gamma interferon (IFN-gamma) mRNA transcription after 3 h of antigen-specific activation of CD8 T cells. For this purpose, we vaccinated C57BL/6 mice subcutaneously with human papillomavirus type 16 L1 virus-like particles and monitored the induction of CD8 T cells specific to the L1(165-173) H-2D(b)-restricted epitope. Comparison of the responses induced in peripheral blood mononuclear cells and lymph nodes (LN) by L1-specific IFN-gamma enzyme-linked immunospot assay and TaqMan determination of the relative increase in L1-specific IFN-gamma mRNA induction normalized to the content of CD8b mRNA showed a significant correlation, despite the difference in the readouts. Most of the cervicovaginal tissues could be analyzed by the TaqMan method if normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA was used and a significant L1-specific IFN-gamma induction was found in one-third of the immunized mice. This local response did not correlate with the immune responses measured in the periphery, with the exception of the sacral LN, an LN draining the genital mucosa, where a significant correlation was found. Our data show that the TaqMan method is sensitive enough to detect antigen-specific CD8 T-cell responses in the genital mucosa of individual mice, and this may contribute to elaborate effective vaccines against genital pathogens.