Decrease in social cohesion in a colonial seabird under a perturbation regime.

Social interactions, through influence on behavioural processes, can play an important role in populations' resilience (i.e. ability to cope with perturbations). However little is known about the effects of perturbations on the strength of social cohesion in wild populations. Long-term associations between individuals may reflect the existence of social cohesion for seizing the evolutionary advantages of social living. We explore the existence of social cohesion and its dynamics under perturbations by analysing long-term social associations, in a colonial seabird, the Audouin's gull Larus audouinii, living in a site experiencing a shift to a perturbed regime. Our goals were namely (1) to uncover the occurrence of long-term social ties (i.e. associations) between individuals and (2) to examine whether the perturbation regime affected this form of social cohesion. We analysed a dataset of more than 3500 individuals from 25 years of monitoring by means of contingency tables and within the Social Network Analysis framework. We showed that associations between individuals are not only due to philopatry or random gregariousness but that there are social ties between individuals over the years. Furthermore, social cohesion decreased under the perturbation regime. We sustain that perturbations may lead not only to changes in individuals' behaviour and fitness but also to a change in populations' social cohesion. The consequences of decreasing social cohesion are still not well understood, but they can be critical for the population dynamics of social species.

Haemosporidian infection and co-infection affect host survival and reproduction in wild populations of great tits.

Theoretical studies predict that parasitic infection may impact host longevity and ultimately modify the trade-off between reproduction and survival. Indeed, a host may adjust its energy allocation in current reproduction to balance the negative effects of parasitism on its survival prospects. However, very few empirical studies tested this prediction. Avian haemosporidian parasites provide an excellent opportunity to assess the influence of parasitic infection on both host survival and reproduction. They are represented by three main genera (Plasmodium, Haemoproteus and Leucocytozoon) and are highly prevalent in many bird populations. Here we provide the first known long-term field study (12 years) to explore the effects of haemosporidian parasite infection and co-infection on fitness in two populations of great tits (Parus major), using a multistate modeling framework. We found that while co-infection decreased survival probability, both infection and co-infection increased reproductive success. This study provides evidence that co-infections can be more virulent than single infections. It also provides support for the life-history theory which predicts that reproductive effort can be adjusted to balance one's fitness when survival prospects are challenged.

Clinical Research Informatics: Contributions from 2016.

Objectives: To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select the best papers published in 2016. Methods: A bibliographic search using a combination of MeSH and free terms on CRI was performed using PubMed, followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. A consensus meeting between the two section editors and the editorial team was organized to finally conclude on the selection of best papers. Results: Among the 452 papers published in 2016 in the various areas of CRI and returned by the query, the full review process selected four best papers. The authors of the first paper utilized a comprehensive representation of the patient medical record and semi-automatically labeled training sets to create phenotype models via a machine learning process. The second selected paper describes an open source tool chain securely connecting ResearchKit compatible applications (Apps) to the widely-used clinical research infrastructure Informatics for Integrating Biology and the Bedside (i2b2). The third selected paper describes the FAIR Guiding Principles for scientific data management and stewardship. The fourth selected paper focuses on the evaluation of the risk of privacy breaches in releasing genomics datasets. Conclusions: A major trend in the 2016 publications is the variety of research on "real-world data" - healthcare-generated data, person health data, and patient-reported outcomes -highlighting the opportunities provided by new machine learning techniques as well as new potential risks of privacy breaches.

Disentangling the role of seed bank and dispersal in plant metapopulation dynamics using patch occupancy surveys.

In plants, the presence of a seed bank challenges the application of classical metapopulation models to aboveground presence surveys; ignoring seed bank leads to overestimated extinction and colonization rates. In this article, we explore the possibility to detect seed bank using hidden Markov models in the analysis of aboveground patch occupancy surveys of an annual plant with limited dispersal. Patch occupancy data were generated by simulation under two metapopulation sizes (N = 200 and N = 1,000 patches) and different metapopulation scenarios, each scenario being a combination of the presence/absence of a 1-yr seed bank and the presence/absence of limited dispersal in a circular 1-dimension configuration of patches. In addition, because local conditions often vary among patches in natural metapopulations, we simulated patch occupancy data with heterogeneous germination rate and patch disturbance. Seed bank is not observable from aboveground patch occupancy surveys, hence hidden Markov models were designed to account for uncertainty in patch occupancy. We explored their ability to retrieve the correct scenario. For 10 yr surveys and metapopulation sizes of N = 200 or 1,000 patches, the correct metapopulation scenario was detected at a rate close to 100%, whatever the underlying scenario considered. For smaller, more realistic, survey duration, the length for a reliable detection of the correct scenario depends on the metapopulation size: 3 yr for N = 1,000 and 6 yr for N = 200 are enough. Our method remained powerful to disentangle seed bank from dispersal in the presence of patch heterogeneity affecting either seed germination or patch extinction. Our work shows that seed bank and limited dispersal generate different signatures on aboveground patch occupancy surveys. Therefore, our method provides a powerful tool to infer metapopulation dynamics in a wide range of species with an undetectable life form.

Advances in methods for estimating stopover duration for migratory species using capture-recapture data.

Many species are migratory, resulting in a life cycle divided into periodic stages occurring in different habitats occupied for a limited amount of time. Estimating the time spent in each habitat is crucial to understanding how individuals modulate their activities and thus to evolutionary ecology and conservation biology. Several methods, including some recent promising advances, can be used to estimate stopover duration as well as arrival and departure probabilities at sites where individuals are monitored using capture-recapture sampling. Our objectives in this study were to (1) describe the available models to estimate stopover duration, (2) illustrate with an original data set what kinds of questions can be addressed using the most recent methods, and (3) to provide in a detailed appendix a practical guide for implementing these methods in E-SURGE software. To illustrate the potential of these models for testing biological hypotheses, we used a capture-recapture data set on marbled newts (Triturus marmoratus). We used time-dependent and time-elapsed-since-arrival effects (using both Markovian and semi-Markov processes for the latter) to model stopover duration and the probability of arriving in and departing from a breeding pond for this species and compared the relative performance of the resulting models. Our findings showed a strong sex effect on stopover duration: females stayed on average 5.63 weeks in a breeding pond whereas males stayed only 3.03 weeks. In both sexes, the retention probability was mainly influenced by the time already spent there. Consequently, individuals of the same sex stayed a similar amount of time in a pond, although they did not arrive simultaneously but successively. The selected data set demonstrated the flexibility of these methods and their potential relevance for applications in evolutionary ecology and conservation.

Clinical Research Informatics Contributions from 2015.

OBJECTIVES: To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select best papers published in 2015. METHOD: A bibliographic search using a combination of MeSH and free terms search over PubMed on Clinical Research Informatics (CRI) was performed followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. A consensus meeting between the two section editors and the editorial team was finally organized to conclude on the selection of best papers. RESULTS: Among the 579 returned papers published in the past year in the various areas of Clinical Research Informatics (CRI) - i) methods supporting clinical research, ii) data sharing and interoperability, iii) re-use of healthcare data for research, iv) patient recruitment and engagement, v) data privacy, security and regulatory issues and vi) policy and perspectives - the full review process selected four best papers. The first selected paper evaluates the capability of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) to support the representation of case report forms (in both the design stage and with patient level data) during a complete clinical study lifecycle. The second selected paper describes a prototype for secondary use of electronic health records data captured in non-standardized text. The third selected paper presents a privacy preserving electronic health record linkage tool and the last selected paper describes how big data use in US relies on access to health information governed by varying and often misunderstood legal requirements and ethical considerations. CONCLUSIONS: A major trend in the 2015 publications is the analysis of observational, "nonexperimental" information and the potential biases and confounding factors hidden in the data that will have to be carefully taken into account to validate new predictive models. In addiction, researchers have to understand complicated and sometimes contradictory legal requirements and to consider ethical obligations in order to balance privacy and promoting discovery.

Information Technology for Clinical, Translational and Comparative Effectiveness Research. Findings from the Yearbook 2015 Section on Clinical Research Informatics.

OBJECTIVES: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. METHOD: We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. RESULTS: The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. CONCLUSIONS: The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their daily practice. All the recent research and development efforts contribute to the challenge of impacting clinically the obtained results towards a personalized medicine.

Information technology for clinical, translational and comparative effectiveness research. Findings from the section clinical research informatics.

OBJECTIVE: To select and summarize key contributions to current research in the field of Clinical Research Informatics (CRI). METHOD: A bibliographic search using a combination of MeSH and free terms search over PubMed was performed followed by a blinded review. RESULTS: The review process resulted in the selection of four papers illustrating various aspects of current research efforts in the area of CRI. The first paper tackles the challenge of extracting accurate phenotypes from Electronic Healthcare Records (EHRs). Privacy protection within shared de-identified, patient-level research databases is the focus of the second selected paper. Two other papers exemplify the growing role of formal representation of clinical data - in metadata repositories - and knowledge - in ontologies - for supporting the process of reusing data for clinical research. CONCLUSIONS: The selected articles demonstrate how concrete platforms are currently achieving interoperability across clinical research and care domains and have reached the evaluation phase. When EHRs linked to genetic data have the potential to shift the research focus from research driven patient recruitment to phenotyping in large population, a key issue is to lower patient re-identification risks for biomedical research databases. Current research illustrates the potential of knowledge engineering to support, in the coming years, the scientific lifecycle of clinical research.

Information technology for clinical, translational and comparative effectiveness research. Findings from the section clinical research informatics.

OBJECTIVES: To summarize advances of excellent current research in the new emerging field of Clinical Research Informatics. METHOD: Synopsis of four key articles selected for the IMIA Yearbook 2013. The selection was performed by querying PubMed and Web of Science with predefined keywords. From the original set of 590 papers, a first subset of 461 articles which was in the scope of Clinical Research Informatics was refined into a second subset of 79 relevant articles from which 15 articles were retained for peer-review. RESULTS: The four selected articles exemplify current research efforts conducted in the areas of data representation and management in clinical trials, secondary use of EHR data for clinical research, information technology platforms for translational and comparative effectiveness research and implementation of privacy control. CONCLUSIONS: The selected articles not only illustrate how innovative information technology supports classically organized randomized controlled trials but also demonstrate that the long promised benefits of electronic health care data for research are becoming a reality through concrete platforms and projects.

A hybrid symbolic-numerical method for determining model structure.

In this article, we present a method for determining whether a model is at least locally identifiable and in the case of non-identifiable models whether any of the parameters are individually at least locally identifiable. This method combines symbolic and numeric methods to create an algorithm that is extremely accurate compared to other numeric methods and computationally inexpensive. A series of generic computational steps are developed to create a method that is ideal for practitioners to use. The algorithm is compared to symbolic methods for two capture-recapture models and a compartment model.

Simple estimation and test procedures in capture-mark-recapture mixed models.

The need to consider in capture-recapture models random effects besides fixed effects such as those of environmental covariates has been widely recognized over the last years. However, formal approaches require involved likelihood integrations, and conceptual and technical difficulties have slowed down the spread of capture-recapture mixed models among biologists. In this article, we evaluate simple procedures to test for the effect of an environmental covariate on parameters such as time-varying survival probabilities in presence of a random effect corresponding to unexplained environmental variation. We show that the usual likelihood ratio test between fixed models is strongly biased, and tends to detect too often a covariate effect. Permutation and analysis of deviance tests are shown to behave properly and are recommended. Permutation tests are implemented in the latest version of program E-SURGE. Our approach also applies to generalized linear mixed models.

Individual heterogeneity in studies on marked animals using numerical integration: capture-recapture mixed models.

In conservation and evolutionary ecology, quantifying and accounting for individual heterogeneity in vital rates of open populations is of particular interest. Individual random effects have been used in capture-recapture models, adopting a Bayesian framework with Markov chain Monte Carlo (MCMC) to carry out estimation and inference. As an alternative, we show how numerical integration via the Gauss-Hermite quadrature (GHQ) can be efficiently used to approximate the capture-recapture model likelihood with individual random effects. We compare the performance of the two approaches (MCMC vs. GHQ) and finite mixture models using two examples, including data on European Dippers and Sociable Weavers. Besides relying on standard statistical tools, GHQ was found to be faster than MCMC simulations. Our approach is implemented in program E-SURGE. Overall, capture recapture mixed models (CR2Ms), implemented either via a GHQ approximation or MCMC simulations, have potential important applications in population biology.

Maximum calorie (sub-threshold) dieting of the obese and its hormonal response.

Severe calorie restriction for treating the obese reduces serum triiodothyronine (T3) and energy expenditure, and may be counterproductive. In order to avoid severe calorie deficiency, we measured the individual minimum energy requirements (threshold, T) in 17 obese females and fed each on a sub-threshold diet, comprising the maximum number of calories commensurate with weight loss (T-200 cals). Mean T-200 was 1318 +/- 96 cals, but the mean weight loss after 16 weeks on a sub-threshold diet (STD) was identical (17 kg) to that obtained by 22 age-matched female controls on a classical diet of 659 +/- 59 cals, exactly half the intake. Weight loss on the classical diet was initially rapid but decelerated sharply after 8 weeks, while on the sub-threshold diet the rate of loss remained constant throughout. In a second study, thyroid hormone measurements were performed three times weekly in 27 obese females during the 4 week period required to establish T. The mean weight loss was 4.02 +/- 0.3 kg, but T3 levels varied minimally and very transiently. STD produces short-term results similar to those obtained by severe calorie deprivation, but is more acceptable to the patient. It appears not to provoke the fat-saving reflexes provoked by the classical, low-calorie diet.