© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term ‘community’ and its specific normative contribution. We argue that ‘community’ is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that (...) taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals’ lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of ‘half knowing’ intrinsic to processes of developing new understandings. (shrink)

The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. At the conditions of pandemic, the success of health care system depends significantly on the regular implementation of effective research tools and population monitoring. The earlier the risks of disease can (...) be identified, the more effective process of preventive measures or treatments can be. This publication is about the creation of a prototype for such a tool within the project «Development of methods, algorithms and intelligent analytical system for processing and analysis of heterogeneous clinical and biomedical data to improve the diagnosis of complex diseases», implementted by the V.M. Glushkov Institute of Cybernetics, National Academy of Sciences of Ukraine, together with the United Institute of Informatics Problems, National Academy of Sciences of Belarus. The insurers, entering the market, can insure mostly low risks by facilitating more frequent changes of insurers by consumers and mixing the overall health insurance market. Socio-demographic variables can be risk adjusters. Since age and gender have a relatively small explanatory power, other socio-demographic variables were studied – marital status, retirement status, disability status, educational level, income level. Because insurers have an interest in beneficial diagnoses for their policyholders, they are also interested in the ability to interpret relevant information – upcoding: insurers can encourage their policyholders to consult with doctors more often to select as many diagnoses as possible. Many countries and health care systems use diagnostic information to determine the reimbursement to a service provider, revealing the necessary data. For processing and analysis of these data, software implementations of construction for classifiers, allocation of informative features, processing of heterogeneous medical and biological variables for carrying out scientific research in the field of clinical medicine are developed. The experience of the use of applied containerized biomedical software tools in cloud environment is summarized. The reproducibility of scientific computing in relation with modern technologies of scientific calculations is discussed. Particularly, attention is paid to containerization of biomedical applications, this permits to get reproducibility of the conditions in which the calculations took place, technologies of software pipelining of calculations, that allows to organize flow calculations, and technologies for parameterization of software environment, that allows to reproduce, if necessary, an identical computing environment. The main approaches to biomedical data preprocessing and integration in the framework of the intelligent analytical system are described. The experience of using the developed linear classifier, gained during its testing on artificial and real data, allows us to conclude about several advantages provided by the containerized form of the created application: it permits to provide access to real data located in cloud environment; it is possible to perform calculations to solve research problems on cloud resources both with the help of developed tools and with the help of cloud services; such a form of research organization makes numerical experiments reproducible, i.e. any other researcher can compare the results of their developments on specific data that have already been studied by others, in order to verify the conclusions and technical feasibility of new results; there exists a universal opportunity to use the developed tools on technical devices of various classes from a personal computer to powerful cluster. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Trafficking and persistence of fetal microchimeric cells (fMCs) and circulating extracellular vesicles (EVs) have been observed in animals and humans, but their consequences in the maternal body and their mechanistic contributions to maternal physiology and pathophysiology are not yet fully defined. Fetal cells and EVs may help remodel maternal organs after pregnancy‐associated changes, but the cell types and EV cargos reaching the mother in preterm pregnancies after exposure to various risk factors can be distinct from term pregnancies. As preterm delivery‐associated (...) maternal complications are rising, revisiting this topic and formulating scientific questions for future research to reduce the risk of maternal morbidities are timely. Epidemiological studies report maternal cardiovascular risk as one of the major complications after preterm delivery. This paper suggests a potential link between fMCs and circulating EVs and adverse maternal cardiovascular outcomes post‐pregnancies, the underlying mechanisms, consequences, and methods for and how this link might be assessed. (shrink)

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.

Fourth-year medical students at the University of Colorado School of Medicine distributed cards to patients in the emergency department asking, "What Worries You Most?" The patients' responses provided insight about their most pressing concerns, often unrelated to their "chief complaints.".

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

In this paper we consider an intuitionistic variant of the modal logic S4 (which we call IS4). The novelty of this paper is that we place particular importance on the natural deduction formulation of IS4— our formulation has several important metatheoretic properties. In addition, we study models of IS4— not in the framework of Kirpke semantics, but in the more general framework of category theory. This allows not only a more abstract definition of a whole class of models but also (...) a means of modelling proofs as well as provability. (shrink)

Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research Consortium. The authors then (...) negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death. (shrink)

In this article, an ethical analysis of an educational programme on renal replacement therapy options for patients and their social network is presented. The two main spearheads of this approach are: (1) offering an educational programme on all renal replacement therapy options ahead of treatment requirement and (2) a home-based approach involving the family and friends of the patient. Arguments are offered for the ethical justification of this approach by considering the viewpoint of the various stakeholders involved. Finally, reflecting on (...) these ethical considerations, essential conditions for carrying out such a programme are outlined. The goal is to develop an ethically justified and responsible educational programme. (shrink)

We introduce and study a natural extension of Marcus external contextual grammars. This mathematically simple mechanism which generates a proper subclass of simple matrix languages, known to be mildly context-sensitive ones, is still mildly context-sensitive. Furthermore, we get an infinite hierarchy of mildly context-sensitive families of languages. Then we attempt to fill a gap regarding the linguistic relevance of these mechanisms which consists in defining a tree structure on the strings generated by many-dimensional external contextual grammars, and investigate some related (...) issues. Several open problems are finally discussed. (shrink)

Before Euro-American settlement, many Native American nations intercropped maize (_Zea mays_), beans (_Phaseolus vulgaris_), and squash (_Cucurbita pepo_) in what is colloquially called the “Three Sisters.” Here we review the historic importance and consequences of rejuvenation of Three Sisters intercropping (3SI), outline a framework to engage Native growers in community science with positive feedbacks to university research, and present preliminary findings from ethnography and a randomized, replicated 3SI experiment. We developed mutually beneficial collaborative research agendas with four Midwestern US Native (...) American nations. Ethnographic data highlighted a culturally based respect for 3SI as living beings, the importance it holds for all cultural facets of these Native nations, and the critical impact the practice has on environmental sustainability. One concern expressed by Native growers during ethnographic research was improving soil health—part of the rationale for establishing the 3SI agronomic experiment. To address this, we collaboratively designed a 3SI experiment. After 1 year, 3SI increased short-term soil respiration by 24%, decreased salt-extractable nitrate by 54%, had no effect on soil microbial biomass (but increased its carbon-to-nitrogen ratio by 32%) compared to the average of monoculture crops. The overarching purpose of this collaborative project is to develop a deeper understanding of 3SI, its cultural importance to Native communities, and how reinvigorating the practice—and intercropping in general—can make agroecosystems more sustainable for people and the environment. (shrink)

2. The equal status mentioned in Thesis 2 need not mean, "equally concrete" or "inclusive," but only, "equally real," where "real" means having a character of its own with reference to which opinions can be true or false. But becoming or process is alone fully concrete or inclusive, since if A is without becoming, and B becomes, then the togetherness of AB also becomes. A new constituent means a new totality. In this sense, becoming is the ultimate principle.

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice (...) of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)