Annual rhythms that underlie phenology: biological time-keeping meets environmental change

Seasonal recurrence of biological processes (phenology) and its relationship to environmental change is recognized as being of key scientific and public concern, but its current study largely overlooks the extent to which phenology is based on biological time-keeping mechanisms. We highlight the relevance of physiological and neurobiological regulation for organisms’ responsiveness to environmental conditions. Focusing on avian and mammalian examples, we describe circannual rhythmicity of reproduction, migration and hibernation, and address responses of animals to photic and thermal conditions. Climate change and urbanization are used as urgent examples of anthropogenic influences that put biological timing systems under pressure. We furthermore propose that consideration of Homo sapiens as principally a ‘seasonal animal’ can inspire new perspectives for understanding medical and psychological problems.     

Dimensionality reduction of longitudinal ’omics data using modern tensor factorizations

Longitudinal ’omics analytical methods are extensively used in the evolving field of precision medicine, by enabling ‘big data’ recording and high-resolution interpretation of complex datasets, driven by individual variations in response to perturbations such as disease pathogenesis, medical treatment or changes in lifestyle. However, inherent technical limitations in biomedical studies often result in the generation of feature-rich and sample-limited datasets. Analyzing such data using conventional modalities often proves to be challenging since the repeated, high-dimensional measurements overload the outlook with inconsequential variations that must be filtered from the data in order to find the true, biologically relevant signal. Tensor methods for the analysis and meaningful representation of multiway data may prove useful to the biological research community by their advertised ability to tackle this challenge. In this study, we present tcam—a new unsupervised tensor factorization method for the analysis of multiway data. Building on top of cutting-edge developments in the field of tensor-tensor algebra, we characterize the unique mathematical properties of our method, namely, 1) preservation of geometric and statistical traits of the data, which enable uncovering information beyond the inter-individual variation that often takes over the focus, especially in human studies. 2) Natural and straightforward out-of-sample extension, making tcam amenable for integration in machine learning workflows. A series of re-analyses of real-world, human experimental datasets showcase these theoretical properties, while providing empirical confirmation of tcam’s utility in the analysis of longitudinal ’omics data.     

Perspectives of clinician and biomedical scientists on interdisciplinary health research

Background

Interdisciplinary health research is a priority of many funding agencies. We surveyed clinician and biomedical scientists about their views on the value and funding of interdisciplinary health research.

Methods

We conducted semistructured interviews with 31 biomedical and 30 clinician scientists. The scientists were selected from the 2000–2006 membership lists of peer-review committees of the Canadian Institutes of Health Research. We investigated respondents’ perspectives on the assumption that collaboration across disciplines adds value to health research. We also investigated their perspectives on funding agencies’ growing support of interdisciplinary research.

Results

The 61 respondents expressed a wide variety of perspectives on the value of interdisciplinary health research, ranging from full agreement (22) to complete disagreement (11) that it adds value; many presented qualified viewpoints (28). More than one-quarter viewed funding agencies’ growing support of interdisciplinary research as appropriate. Most (44) felt that the level of support was unwarranted. Arguments included the belief that current support leads to the creation of artificial teams and that a top-down process of imposing interdisciplinary structures on teams constrains scientists’ freedom. On both issues we found contrasting trends between the clinician and the biomedical scientists.

Interpretation

Despite having some positive views about the value of interdisciplinary research, scientists, especially biomedical scientists, expressed reservations about the growing support of interdisciplinary research.Collaboration between health disciplines is a new priority of research institutions and funding agencies. Many of these agencies have undergone restructuring and have developed programs specifically to intensify interdisciplinary research. In 2007, the US National Institutes of Health created 9 interdisciplinary research consortia “as a means of integrating aspects of different disciplines to address health challenges that have been resistant to traditional research approaches.”¹ In 2000, the Canadian Institutes of Health Research (CIHR) was established with an express mandate “to forge a health research agenda across disciplines, sectors, and regions that embraces scientific opportunity and reflects the emerging health needs of Canadians, the evolution of the health care system and the information needs of health policy decision-makers.”²This change in priority has been attributed to 3 main factors: the need to answer complex health problems, the need to explore questions that are not confined to a single discipline and the need to provide effective solutions to societal problems.^3,4 Although the arguments advocating for interdisciplinary health research have evoked many kinds of promises, scientists undertaking collaborative research can also face many challenges. The past 10 years have seen a growing body of literature examining the impediments and facilitators to interdisciplinary collaboration.^3,5–14Despite this growing interest, little is known about scientists’ opinions on the prevalent assumption that working across disciplines adds value to health research. Moreover, little consideration has been given to how scientists perceive the growing support of interdisciplinary research by funding agencies. In a survey commissioned by the CIHR, 36% of funded researchers indicated that their collaboration across disciplines had increased as a result of the agency’s establishment.¹⁵ Whether this shift reflects researchers’ scientific interests or their attempts to secure funding by appealing to the agency’s policy of promoting interdisciplinary research is unknown.As part of a broad research program investigating the integration of social science in health research,¹⁶ we conducted this study to examine to what extent, and why, biomedical and clinician scientists are for or against the promotion of interdisciplinary research. We targeted these types of scientists because they were predominantly affected by the move toward interdisciplinary research that occurred after the creation of the CIHR.     

White adipose tissue reference network: a knowledge resource for exploring health-relevant relations

Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity—from molecular, to physiological, to social. Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data. A White Adipose Tissue Health Reference Network (WATRefNet) was constructed as a resource for discovery and prioritization of mechanism-based biomarkers for white adipose tissue (WAT) health status and the effect of food and drug compounds on WAT health status. The WATRefNet (6,797 nodes and 32,171 edges) is based on (1) experimental data obtained from 10 studies addressing different adiposity states, (2) seven public knowledge bases of molecular interactions, (3) expert’s definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and (4) a collection of relevant biomarkers of these processes identified by BIOCLAIMS (http://bioclaims.uib.es). The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions. We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes. Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet. This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0439-x) contains supplementary material, which is available to authorized users.     

Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems

The use of human and veterinary pharmaceuticals is increasing. Over the past decade, there has been a proliferation of research into potential environmental impacts of pharmaceuticals in the environment. A Royal Society-supported seminar brought together experts from diverse scientific fields to discuss the risks posed by pharmaceuticals to wildlife. Recent analytical advances have revealed that pharmaceuticals are entering habitats via water, sewage, manure and animal carcases, and dispersing through food chains. Pharmaceuticals are designed to alter physiology at low doses and so can be particularly potent contaminants. The near extinction of Asian vultures following exposure to diclofenac is the key example where exposure to a pharmaceutical caused a population-level impact on non-target wildlife. However, more subtle changes to behaviour and physiology are rarely studied and poorly understood. Grand challenges for the future include developing more realistic exposure assessments for wildlife, assessing the impacts of mixtures of pharmaceuticals in combination with other environmental stressors and estimating the risks from pharmaceutical manufacturing and usage in developing countries. We concluded that an integration of diverse approaches is required to predict ‘unexpected’ risks; specifically, ecologically relevant, often long-term and non-lethal, consequences of pharmaceuticals in the environment for wildlife and ecosystems.     

Perceived social isolation,evolutionary fitness and health outcomes: a lifespan approach

Sociality permeates each of the fundamental motives of human existence and plays a critical role in evolutionary fitness across the lifespan. Evidence for this thesis draws from research linking deficits in social relationship—as indexed by perceived social isolation (i.e. loneliness)—with adverse health and fitness consequences at each developmental stage of life. Outcomes include depression, poor sleep quality, impaired executive function, accelerated cognitive decline, unfavourable cardiovascular function, impaired immunity, altered hypothalamic pituitary–adrenocortical activity, a pro-inflammatory gene expression profile and earlier mortality. Gaps in this research are summarized with suggestions for future research. In addition, we argue that a better understanding of naturally occurring variation in loneliness, and its physiological and psychological underpinnings, in non-human species may be a valuable direction to better understand the persistence of a ‘lonely’ phenotype in social species, and its consequences for health and fitness.     

From Research to Practice: Which Research Strategy Contributes More to Clinical Excellence? Comparing High-Volume versus High-Quality Biomedical Research

The question when and to what extent academic research can benefit society is of great interest to policy-makers and the academic community. Physicians in university hospitals represent a highly relevant test-group for studying the link between research and practice because they engage in biomedical academic research while also providing medical care of measurable quality. Physicians’ research contribution to medical practice can be driven by either high-volume or high-quality research productivity, as often pursuing one productivity strategy excludes the other. To empirically examine the differential contribution to medical practice of the two strategies, we collected secondary data on departments across three specializations (Cardiology, Oncology and Orthopedics) in 50 U.S.-based university hospitals served by 4,330 physicians. Data on volume and quality of biomedical research at each department was correlated with publicly available ratings of departments’ quality of care, demonstrating that high-quality research has significantly greater contribution to quality of care than high-volume research.     

The Effects of Measuring Emotion: Physiological Reactions to Emotional Situations Depend on whether Someone Is Asking

Measurement effects exist throughout the sciences–the act of measuring often changes the properties of the observed. We suggest emotion research is no exception. The awareness and conscious assessment required by self-report of emotion may significantly alter emotional processes. In this study, participants engaged in a difficult math task designed to induce anger or shame while their cardiovascular responses were measured. Half of the participants were asked to report on their emotional states and appraise their feelings throughout the experiment, whereas the other half completed a control questionnaire. Among those in the anger condition, participants assigned to report on their emotions exhibited qualitatively different physiological responses from those who did not report. For participants in the shame condition, there were no significant differences in physiology based on the self-report manipulation. The study demonstrates that the simple act of reporting on an emotional state may have a substantial impact on the body’s reaction to an emotional situation.     

Dysbiotic drift: mental health,environmental grey space,and microbiota

Advances in research concerning the mental health implications of dietary patterns and select nutrients have been remarkable. At the same time, there have been rapid increases in the understanding of the ways in which non-pathogenic microbes can potentially influence many aspects of human health, including those in the mental realm. Discussions of nutrition and microbiota are often overlapping. A separate, yet equally connected, avenue of research is that related to natural (for example, green space) and built environments, and in particular, how they are connected to human cognition and behaviors. It is argued here that in Western industrial nations a ‘disparity of microbiota’ might be expected among the socioeconomically disadvantaged, those whom face more profound environmental forces. Many of the environmental forces pushing against the vulnerable are at the neighborhood level. Matching the developing microbiome research with existing environmental justice research suggests that grey space may promote dysbiosis by default. In addition, the influence of Westernized lifestyle patterns, and the marketing forces that drive unhealthy behaviors in deprived communities, might allow dysbiosis to be the norm rather than the exception in those already at high risk of depression, subthreshold (subsyndromal) conditions, and subpar mental health. If microbiota are indeed at the intersection of nutrition, environmental health, and lifestyle medicine (as these avenues pertain to mental health), then perhaps the rapidly evolving gut-brain-microbiota conversation needs to operate through a wider lens. In contrast to the more narrowly defined psychobiotic, the term eco-psychotropic is introduced.     

The Role of Walkers’ Needs and Expectations in Supporting Maintenance of Attendance at Walking Groups: A Longitudinal Multi-Perspective Study of Walkers and Walk Group Leaders

Background

There is good evidence that when people’s needs and expectations regarding behaviour change are met, they are satisfied with that change, and maintain those changes. Despite this, there is a dearth of research on needs and expectations of walkers when initially attending walking groups and whether and how these needs and expectations have been satisfied after a period of attendance. Equally, there is an absence of research on how people who lead these groups understand walkers’ needs and walk leaders’ actions to address them. The present study was aimed at addressing both of these gaps in the research.

Methods

Two preliminary thematic analyses were conducted on face-to-face interviews with (a) eight walkers when they joined walking groups, five of whom were interviewed three months later, and (b) eight walk leaders. A multi-perspective analysis building upon these preliminary analyses identified similarities and differences within the themes that emerged from the interviews with walkers and walk leaders.

Results

Walkers indicated that their main needs and expectations when joining walking groups were achieving long-term social and health benefits. At the follow up interviews, walkers indicated that satisfaction with meeting similar others within the groups was the main reason for continued attendance. Their main source of dissatisfaction was not feeling integrated in the existing walking groups. Walk leaders often acknowledged the same reasons for walkers joining and maintaining attendance at walking. However, they tended to attribute dissatisfaction and drop out to uncontrollable environmental factors and/or walkers’ personalities. Walk leaders reported a lack of efficacy to effectively address walkers’ needs.

Conclusions

Interventions to increase retention of walkers should train walk leaders with the skills to help them modify the underlying psychological factors affecting walkers’ maintenance at walking groups. This should result in greater retention of walkers in walking groups, thereby allowing walkers to receive the long-term social and health benefits of participation in these groups.     

A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data

Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn’t been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.     

ConfocalCheck - A Software Tool for the Automated Monitoring of Confocal Microscope Performance

Laser scanning confocal microscopy has become an invaluable tool in biomedical research but regular quality testing is vital to maintain the system’s performance for diagnostic and research purposes.Although many methods have been devised over the years to characterise specific aspects of a confocal microscope like measuring the optical point spread function or the field illumination, only very few analysis tools are available. Our aim was to develop a comprehensive quality assurance framework ranging from image acquisition to automated analysis and documentation. We created standardised test data to assess the performance of the lasers, the objective lenses and other key components required for optimum confocal operation.The ConfocalCheck software presented here analyses the data fully automatically. It creates numerous visual outputs indicating potential issues requiring further investigation. By storing results in a web browser compatible file format the software greatly simplifies record keeping allowing the operator to quickly compare old and new data and to spot developing trends.We demonstrate that the systematic monitoring of confocal performance is essential in a core facility environment and how the quantitative measurements obtained can be used for the detailed characterisation of system components as well as for comparisons across multiple instruments.     

Cleaning Products,Environmental Awareness and Risk Perception in Mérida,Mexico

Cleaning products are associated with many health and environmental problems. Contamination of water resources by cleaning products is more likely to occur with septic tanks as sewage treatment systems especially in karstic terrains. We explored women’s ideas about water sources and the risk cleaning products pose to health and sewage in Mérida, a city in the Yucatán peninsula of Mexico. Women were unaware of the city’s water management system. We found a positive and statistically significant association between risk perception and environmental awareness, education level and employment status. We suggest developing education and risk communication strategies to inform residents about the hydro-geological features in the Yucatán, the vulnerability of its karstic aquifer and the health and environmental risks associated with cleaning agents.     

PRIME: a graphical interface for integrating genomic/proteomic databases

Data mining, finding and integration of information about proteins of interest, is an essential component in modern biological and biomedical research. Even when focusing on a single organism and only on a small number of proteins, there are often dozens fo data sources containing relevant information. We are developing PRIME, a protein information environment, to serve as a virtual central database which integrates distributed heterogeneous information about proteins (linked by common identifier). PRIME has powerful capabilities to visualize all kinds of protein annotation in specialized views. These views can be displayed side by side at the same time and can be synchronized in order to show simultaneously different aspects of identical proteins. These features allow a quick and comprehensive overview of properties of single proteins or protein sets.     

Improving Environmental Sanitation, Health, and Well-Being: A Conceptual Framework for Integral Interventions

We introduce a conceptual framework for improving health and environmental sanitation in urban and peri-urban areas using an approach combining health, ecological, and socioeconomic and cultural assessments. The framework takes into account the three main components: i) health status, ii) physical environment, and iii) socioeconomic and cultural environment. Information on each of these three components can be obtained by using standard disciplinary methods and an innovative combination of these methods. In this way, analyses lead to extended characterization of health, ecological, and social risks while allowing the comprehensive identification of critical control points (CCPs) in relation to biomedical, epidemiological, ecological, and socioeconomic and cultural factors. The proposed concept complements the conventional CCP approach by including an actor perspective that considers vulnerability to risk and patterns of resilience. Interventions deriving from the comprehensive analysis consider biomedical, engineering, and social science perspectives, or a combination of them. By this way, the proposed framework jointly addresses health and environmental sanitation improvements, and recovery and reuse of natural resources. Moreover, interventions encompass not only technical solutions but also behavioral, social, and institutional changes which are derived from the identified resilience patterns. The interventions are assessed with regards to their potential to eliminate or reduce specific risk factors and vulnerability, enhance health status, and assure equity. The framework is conceptualized and validated for the context of urban and peri-urban settings in developing countries focusing on waste, such as excreta, wastewater, and solid waste, their influence on food quality, and their related pathogens, nutrients, and chemical pollutants.     

Using the International Classification of Functioning,Disability and Health (ICF) to Describe Children Referred to Special Care or Paediatric Dental Services

Children in dentistry are traditionally described in terms of medical diagnosis and prevalence of oral disease. This approach gives little information regarding a child’s capacity to maintain oral health or regarding the social determinants of oral health. The biopsychosocial approach, embodied in the International Classification of Functioning, Disability and Health - Child and Youth version (ICF-CY) (WHO), provides a wider picture of a child’s real-life experience, but practical tools for the application of this model are lacking. This article describes the preliminary empirical study necessary for development of such a tool - an ICF-CY Core Set for Oral Health. An ICF-CY questionnaire was used to identify the medical, functional, social and environmental context of 218 children and adolescents referred to special care or paediatric dental services in France, Sweden, Argentina and Ireland (mean age 8 years ±3.6yrs). International Classification of Disease (ICD-10) diagnoses included disorders of the nervous system (26.1%), Down syndrome (22.0%), mental retardation (17.0%), autistic disorders (16.1%), and dental anxiety alone (11.0%). The most frequently impaired items in the ICF Body functions domain were ‘Intellectual functions’, ‘High-level cognitive functions’, and ‘Attention functions’. In the Activities and Participation domain, participation restriction was frequently reported for 25 items including ‘Handling stress’, ‘Caring for body parts’, ‘Looking after one’s health’ and ‘Speaking’. In the Environment domain, facilitating items included ‘Support of friends’, ‘Attitude of friends’ and ‘Support of immediate family’. One item was reported as an environmental barrier – ‘Societal attitudes’. The ICF-CY can be used to highlight common profiles of functioning, activities, participation and environment shared by children in relation to oral health, despite widely differing medical, social and geographical contexts. The results of this empirical study might be used to develop an ICF-CY Core Set for Oral Health - a holistic but practical tool for clinical and epidemiological use.     

Sex-Related Online Behaviors,Perceived Peer Norms and Adolescents’ Experience with Sexual Behavior: Testing an Integrative Model

Research on the role of sex-related Internet use in adolescents’ sexual development has often isolated the Internet and online behaviors from other, offline influencing factors in adolescents’ lives, such as processes in the peer domain. The aim of this study was to test an integrative model explaining how receptive (i.e., use of sexually explicit Internet material [SEIM]) and interactive (i.e., use of social networking sites [SNS]) sex-related online behaviors interrelate with perceived peer norms in predicting adolescents’ experience with sexual behavior. Structural equation modeling on longitudinal data from 1,132 Dutch adolescents (M_age T₁ = 13.95; range 11-17; 52.7% boys) demonstrated concurrent, direct, and indirect effects between sex-related online behaviors, perceived peer norms, and experience with sexual behavior. SEIM use (among boys) and SNS use (among boys and girls) predicted increases in adolescents’ perceptions of peer approval of sexual behavior and/or in their estimates of the numbers of sexually active peers. These perceptions, in turn, predicted increases in adolescents’ level of experience with sexual behavior at the end of the study. Boys’ SNS use also directly predicted increased levels of experience with sexual behavior. These findings highlight the need for multisystemic research and intervention development to promote adolescents’ sexual health.     

Species,Habitats, Society: An Evaluation of Research Supporting EU's Natura 2000 Network

The Natura 2000 network is regarded as one of the conservation success stories in the global effort to protect biodiversity. However, significant challenges remain in Natura 2000 implementation, owing to its rapid expansion, and lack of a coherent vision for its future. Scientific research is critical for identifying conservation priorities, setting management goals, and reconciling biodiversity protection and society in the complex political European landscape. Thus, there is an urgent need for a comprehensive evaluation of published Natura 2000 research to highlight prevalent research themes, disciplinary approaches, and spatial entities. We conducted a systematic review of 572 scientific articles and conference proceedings focused on Natura 2000 research, published between 1996 and 2014. We grouped these articles into ‘ecological’ and ‘social and policy’ categories. Using a novel application of network analysis of article keywords, we found that Natura 2000 research forms a cohesive small-world network, owing to the emphasis on ecological research (79% of studies, with a strong focus on spatial conservation planning), and the underrepresentation of studies addressing ‘social and policy’ issues (typically focused on environmental impact assessment, multi-level governance, agri-environment policy, and ecosystem services valuation). ‘Ecological’ and ‘social and policy’ research shared only general concepts (e.g., Natura 2000, Habitats Directive) suggesting a disconnection between these disciplines. The UK and the Mediterranean basin countries dominated Natura 2000 research, and there was a weak correlation between number of studies and proportion of national territory protected. Approximately 40% of ‘social and policy’ research and 26% of ‘ecological’ studies highlighted negative implications of Natura 2000, while 21% of studies found positive social and biodiversity effects. We emphasize the need for designing inter- and transdisciplinary research in order to promote a social-ecological understanding of Natura 2000, and advance EU conservation policies.     

Ecosystem health as measured from the molecular to the community level of organization,with reference to sediment bioassessment

The current recognition that chemical measurements are uncertain indicators of biological consequences of pollution has shifted the emphasis away from assessing environmental chemistry alone toward the inclusion of measurements of the health of organisms. Effects of pollutants begin with the individual, have subsequent repercussions on population level processes, and ramifications for community structure and functions. Pollutants act at a molecular level and the biochemical lesions is the first step in the manifestation of effects. Technologies that operate at the cellular level assist in elucidating toxicity. Higher levels of integration include an organism's capacity for growth. Laboratory bioassays andin situ research can monitor physiological incapacities and assist in predicting population level effects. A yet higher level of organization is that of the ecological community.