Project description:Successful navigation is fundamental to the survival of nearly every animal on earth, and achieved by nervous systems of vastly different sizes and characteristics. Yet surprisingly little is known of the detailed neural circuitry from any species which can accurately represent space for navigation. Path integration is one of the oldest and most ubiquitous navigation strategies in the animal kingdom. Despite a plethora of computational models, from equational to neural network form, there is currently no consensus, even in principle, of how this important phenomenon occurs neurally. Recently, all path integration models were examined according to a novel, unifying classification system. Here we combine this theoretical framework with recent insights from directed walk theory, and develop an intuitive yet mathematically rigorous proof that only one class of neural representation of space can tolerate noise during path integration. This result suggests many existing models of path integration are not biologically plausible due to their intolerance to noise. This surprising result imposes significant computational limitations on the neurobiological spatial representation of all successfully navigating animals, irrespective of species. Indeed, noise-tolerance may be an important functional constraint on the evolution of neuroarchitectural plans in the animal kingdom.
Project description:Both the occurrence and intensity of facial expressions are critical to what the face reveals. While much progress has been made towards the automatic detection of facial expression occurrence, controversy exists about how to estimate expression intensity. The most straight-forward approach is to train multiclass or regression models using intensity ground truth. However, collecting intensity ground truth is even more time consuming and expensive than collecting binary ground truth. As a shortcut, some researchers have proposed using the decision values of binary-trained maximum margin classifiers as a proxy for expression intensity. We provide empirical evidence that this heuristic is flawed in practice as well as in theory. Unfortunately, there are no shortcuts when it comes to estimating smile intensity: researchers must take the time to collect and train on intensity ground truth. However, if they do so, high reliability with expert human coders can be achieved. Intensity-trained multiclass and regression models outperformed binary-trained classifier decision values on smile intensity estimation across multiple databases and methods for feature extraction and dimensionality reduction. Multiclass models even outperformed binary-trained classifiers on smile occurrence detection.
Project description:This paper attempts to reconcile critics and defenders of inclusive fitness by constructing a synthesis that does justice to the insights of both. I argue that criticisms of the regression-based version of Hamilton's rule, although they undermine its use for predictive purposes, do not undermine its use as an organizing framework for social evolution research. I argue that the assumptions underlying the concept of inclusive fitness, conceived as a causal property of an individual organism, are unlikely to be exactly true in real populations, but they are approximately true given a specific type of weak selection that Hamilton took, on independent grounds, to be responsible for the cumulative assembly of complex adaptation. Finally, I reflect on the uses and limitations of 'design thinking' in social evolution research.
Project description:BACKGROUND: Our randomized controlled trial (The BETTER Trial) found that training a clinician to become a Prevention Practitioner (PP) in family practices improved chronic disease prevention and screening (CDPS). PPs were trained on CDPS and provided prevention prescriptions tailored to participating patients. For this embedded qualitative study, we explored perceptions of this new role to understand the PP intervention. METHODS: We used grounded theory methodology and purposefully sampled participants involved in any capacity with the BETTER Trial. Two physicians and one coordinator in each of two cities (Toronto, Ontario and Edmonton, Alberta) conducted eight individual semi-structured interviews and seven focus groups. We used an interview guide and documented research activities through an audit trail, journals, field notes and memos. We analyzed the data using the constant comparative method throughout open coding followed by theoretical coding. RESULTS: A framework and process involving external and internal practice facilitation using the new role of PP was thought to impact CDPS. The PP facilitated CDPS through on-going relationships with patients and practice team members. Key components included: 1) approaching CDPS in a comprehensive manner, 2) an individualized and personalized approach at multiple levels, 3) integrated continuity that included linking the patients and practices to CPDS resources, and 4) adaptability to different practices and settings. CONCLUSIONS: The BETTER framework and key components are described as impacting CDPS through a process that involved a new role, the PP. The introduction of a novel role of a clinician within the primary care practice with skills in CDPS could appropriately address gaps in prevention and screening.
Project description:Our knowledge of proteins has greatly improved in recent years, driven by new technologies in the fields of molecular biology and proteome research. It has become clear that from a single gene not only one single gene product but many different ones - termed protein species - are generated, all of which may be associated with different functions. Nonetheless, an unambiguous nomenclature for describing individual protein species is still lacking. With the present paper we therefore propose a systematic nomenclature for the comprehensive description of protein species. The protein species nomenclature is flexible and adaptable to every level of knowledge and of experimental data in accordance with the exact chemical composition of individual protein species. As a minimum description the entry name (gene name + species according to the UniProt knowledgebase) can be used, if no analytical data about the target protein species are available.
Project description:Repression is associated in the literature with terms such as non-expression, emotional control, rationality, anti-emotionality, defensiveness and restraint. Whether these terms are synonymous with repression, indicate a variation, or are essentially different from repression is uncertain. To clarify this obscured view on repression, this paper indicates the similarities and differences between these concepts. Repression is the general term that is used to describe the tendency to inhibit the experience and the expression of negative feelings or unpleasant cognitions in order to prevent one's positive self-image from being threatened ('repressive coping style'). The terms self-deception versus other-deception, and socially related versus personally related repression refer to what is considered to be different aspects of repression. Defensiveness is a broader concept that includes both anxious defensiveness and repression; the essential difference is whether negative emotions are reported or not. Concepts that are sometimes associated with repression, but which are conceptually different, are also discussed in this paper: The act of suppression, 'repressed memories,' habitual suppression, concealment, type C coping pattern, type D personality, denial, alexithymia and blunting. Consequences for research: (1) When summarizing findings reported in the literature, it is essential to determine which concepts the findings represent. This is rarely made explicit, and failure to do so may lead to drawing the wrong conclusions (2) It is advisable to use scales based on different aspects of repression (3) Whether empirical findings substantiate the similarities and differences between concepts described in this paper will need to be shown.
Project description:Recent observations suggest a potential pathophysiological function for adenosine signalling in chronic inflammation of the airways, and development of new selective agonists or antagonists for adenosine receptor subtypes has recently lead to a number of clinical trials of such agents in asthma. The review by Wilson in this issue of the BJP provides a critical perspective on adenosine receptors as rational targets for drug development for anti-asthma drugs with a focus on their efficacy and safety. Important conclusions can be drawn about the function of adenosine receptors in human asthma and approaches to these important targets with novel therapeutic agents.
Project description:Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.
Project description:Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the "UK Biobank," which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which "process" expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.