Parents’ experiences of caring for a young person with neurofibromatosis type 1 (NF1): a qualitative study

Neurofibromatosis type 1 (NF1) is a variable and unpredictable genetic condition that can lead to changes to an individual’s appearance. Research has started to explore children’s and young people’s experiences of living with the condition; however, there is a lack of research with parents. This exploratory qualitative study set out to examine parents’ experiences of caring for a young person with NF1. Seven parents took part in semi structured interviews which were subjected to a thematic analysis. Three key themes were identified which related to managing the uncertainty of the condition, the impact of an altered appearance, and others’ awareness and understanding of NF1. Parents felt that understanding NF1 themselves in order to support their child was beneficial whilst a perceived lack of understanding by others was cited as a significant challenge. Parents require trustworthy information and also more widely call for greater understanding and awareness of the condition

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Contribution of Distinct Homeodomain DNA Binding Specificities to Drosophila Embryonic Mesodermal Cell-Specific Gene Expression Programs

Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I–HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks directing mesoderm development.National Institutes of Health (U.S.) (Grant R01 HG005287

The Mathematical Universe

I explore physics implications of the External Reality Hypothesis (ERH) that there exists an external physical reality completely independent of us humans. I argue that with a sufficiently broad definition of mathematics, it implies the Mathematical Universe Hypothesis (MUH) that our physical world is an abstract mathematical structure. I discuss various implications of the ERH and MUH, ranging from standard physics topics like symmetries, irreducible representations, units, free parameters, randomness and initial conditions to broader issues like consciousness, parallel universes and Godel incompleteness. I hypothesize that only computable and decidable (in Godel's sense) structures exist, which alleviates the cosmological measure problem and help explain why our physical laws appear so simple. I also comment on the intimate relation between mathematical structures, computations, simulations and physical systems.Comment: Replaced to match accepted Found. Phys. version, 31 pages, 5 figs; more details at http://space.mit.edu/home/tegmark/toe.htm

Collaborating with individuals with lived experience to adapt CANMAT clinical depression guidelines into a patient treatment guide: The CHOICE‐D co‐design process

Effective treatment of depression involves collaboration with informed patients and families and appropriate knowledge sharing. We describe here our experience, as a case example, of a collaboration to “translate” a clinical guideline designed for practitioners into an accessible, plainlanguage version that patients and families can use during the care process, both to provide basic educational information and to foster informed discussions with their treatment providers. Content experts in knowledge translation, patient advocacy, patient‐oriented research, and psychiatry guided overall project design. Our first step was to identify lived experience writers to join in the codesign and co‐writing of the “CHOICE‐D Patient and Family Guide to Depression Treatment.” A national call for writers attracted 62 applicants, from whom eight individuals with lived experience of depression and writing experience were selected. Individuals subsequently attended a welcoming teleconference, followed by a 1‐day workshop designed to provide (a) a detailed overview of the clinician guideline, (b) an opportunity to select what should be included in the Guide, and (c) key principles of knowledge translation/lay writing. Both from the workshop and subsequently through the codesign process, lived experience writers recommended that the Guide address symptoms, effects of illness course on treatment, first‐line treatments, safety/side effects, and treatment misconceptions. To promote patient autonomy, question scripts (how and what to ask your treatment provider), self‐triaging resources, and treatment selection aids were suggested. Stylistic considerations included use of simple yet hopeful language, brevity, white space, key terms glossary, and graphics. Several strategies were particularly useful to optimize writer engagement in the codesign process: a pre‐workshop conference call and circulation of project resources, an in‐person workshop to increase content knowledge, structured discussion with co‐writers and project leads to develop ideas, and practical training exercises with the provision of feedback. Both during and at the end of the project, writers provided additional recommendations for improving the process, including more in‐person meetings, distribution of step‐by‐step instructions on the writing task, and a key terms glossary of technical terms to support their role. In conclusion, we describe a process with practical tips and reflective feedback on important considerations for engaging persons with lived experience as leaders in the codesign and writing process of lay treatment guidelines. These methods may serve as a model for similar projects in other areas of healthcare.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156154/2/jep13308.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156154/1/jep13308_am.pd

Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10−8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD

Information retrieval and text mining technologies for chemistry

Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.A.V. and M.K. acknowledge funding from the European Community’s Horizon 2020 Program (project reference: 654021 - OpenMinted). M.K. additionally acknowledges the Encomienda MINETAD-CNIO as part of the Plan for the Advancement of Language Technology. O.R. and J.O. thank the Foundation for Applied Medical Research (FIMA), University of Navarra (Pamplona, Spain). This work was partially funded by Consellería de Cultura, Educación e Ordenación Universitaria (Xunta de Galicia), and FEDER (European Union), and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). We thank Iñigo Garciá -Yoldi for useful feedback and discussions during the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Leo Strauss and International Relations: The politics of modernity's abyss

This article argues that an engagement with the political philosophy of Leo Strauss is of considerable value in International Relations (IR), in relation to the study of both recent US foreign policy and contemporary IR theory. The question of Straussian activities within and close to the foreign policy-making establishment in the United States during the period leading up to the 2003 invasion of Iraq has been the focus of significant scholarly and popular attention in recent years. This article makes the case that several individuals influenced by Strauss exercised considerable influence in the fields of intelligence production, the media and think tanks, and traces the ways in which elements of Strauss’ thought are discernible in their interventions in these spheres. It further argues that Strauss’ political philosophy is of broader significance for IR insofar as it can be read as a securitising response to the dangers he associated with the foundationlessness of the modern condition. The article demonstrates that the politics of this response are of crucial importance for contemporary debates between traditional and critical IR theorists