Advantage of Animal Models with Metabolic Flexibility for Space Research Beyond Low Earth Orbit

As the worlds space agencies and commercial entities continue to expand beyond Low Earth Orbit (LEO), novel approaches to carry out biomedical experiments with animals are required to address the challenge of adaptation to space flight and new planetary environments. The extended time and distance of space travel along with reduced involvement of Earth-based mission support increases the cumulative impact of the risks encountered in space. To respond to these challenges, it becomes increasingly important to develop the capability to manage an organisms self-regulatory control system, which would enable survival in extraterrestrial environments. To significantly reduce the risk to animals on future long duration space missions, we propose the use of metabolically flexible animal models as pathfinders, which are capable of tolerating the environmental extremes exhibited in spaceflight, including altered gravity, exposure to space radiation, chemically reactive planetary environments and temperature extremes.In this report we survey several of the pivotal metabolic flexibility studies and discuss the importance of utilizing animal models with metabolic flexibility with particular attention given to the ability to suppress the organism's metabolism in spaceflight experiments beyond LEO. The presented analysis demonstrates the adjuvant benefits of these factors to minimize damage caused by exposure to spaceflight and extreme planetary environments. Examples of microorganisms and animal models with dormancy capabilities suitable for space research are considered in the context of their survivability under hostile or deadly environments outside of Earth. Potential steps toward implementation of metabolic control technology in spaceflight architecture and its benefits for animal experiments and manned space exploration missions are discussed

Explanations for functional somatic symptoms across European treatment settings: a mixed methods study

Objective Engaging patients in treatment for functional somatic symptoms (FSS) relies on a shared understanding of the mechanisms underlying the complaints. Despite this, little is known about the explanatory models used in daily clinical practice. We aim to examine the approaches healthcare professionals use to explain FSS across European healthcare settings. Methods This is an exploratory mixed methods study, combining sequential qualitative and quantitative analyses. 3 types of data were collected: a survey of Health-Care Professionals (HCPs) with special interest in FSS from 16 European countries (n = 186), Patient Education Material collected systematically from survey respondents (n = 72) and semi-structured Interviews with HCPs (n = 14). Survey results are summarized descriptively. Qualitative data was thematically coded following template analysis methods. Findings were integrated through mixed-methods triangulation. Results Five main explanatory models for FSS that are used across treatment settings and diagnostic constructs were represented in the data. The ‘Multisystem Stress’ Approach explains FSS through physiological stress responses within a bio-psycho-social paradigm. ‘Sensitized Alarm’ and ‘Malfunctioning software’ are both approaches derived from the neurosciences. Explanations related to ‘Embodied Experience’ are often used within integrated psychosomatic therapies. In the person-centred ‘Symptoms’ approach, HCPs aim for co-constructed, individualized explanations. These approaches, which rely on different models of mind-body-environment are complementary and are used flexibly by skilled HCPs. Conclusion Taken together the explanatory models described might form the basis of a curriculum of medical explanation with the potential to equip clinicians to form more collaborative relationships with patients across healthcare

GeneLab: NASA's Open Access, Collaborative Platform for Systems Biology and Space Medicine

NASA is investing in GeneLab1 (http:genelab.nasa.gov), a multi-year effort to maximize utilization of the limited resources to conduct biological and medical research in space, principally aboard the International Space Station (ISS). High-throughput genomic, transcriptomic, proteomic or other omics analyses from experiments conducted on the ISS will be stored in the GeneLab Data Systems (GLDS), an open-science information system that will also include a biocomputation platform with collaborative science capabilities, to enable the discovery and validation of molecular networks

Using Residential History and Groundwater Modeling to Examine Drinking Water Exposure and Breast Cancer

BACKGROUND. Spatial analyses of case-control data have suggested a possible link between breast cancer and groundwater plumes in upper Cape Cod, Massachusetts. OBJECTIVE. We integrated residential histories, public water distribution systems, and groundwater modeling within geographic information systems (GIS) to examine the association between exposure to drinking water that has been contaminated by wastewater effluent and breast cancer. METHODS. Exposure was assessed from 1947 to 1993 for 638 breast cancer cases who were diagnosed from 1983 to 1993 and 842 controls; we took into account residential mobility and drinking water source. To estimate the historical impact of effluent on drinking water wells, we modified a modular three-dimensional finite-difference groundwater model (MODFLOW) from the U.S. Geological Survey. The analyses included latency and exposure duration. RESULTS. Wastewater effluent impacted the drinking water wells of study participants as early as 1966. For > 0-5 years of exposure (versus no exposure), associations were generally null. Adjusted odds ratios (AORs) for > 10 years of exposure were slightly increased, assuming latency periods of 0 or 10 years [AOR = 1.3; 95% confidence interval (CI), 0.9-1.9 and AOR = 1.6; 95% CI, 0.8-3.2, respectively]. Statistically significant associations were estimated for ever-exposed versus never-exposed women when a 20-year latency period was assumed (AOR = 1.9; 95% CI, 1.0-3.4). A sensitivity analysis that classified exposures assuming lower well-pumping rates showed similar results. CONCLUSION. We investigated the hypothesis generated by earlier spatial analyses that exposure to drinking water contaminated by wastewater effluent may be associated with breast cancer. Using a detailed exposure assessment, we found an association with breast cancer that increased with longer latency and greater exposure duration.National Cancer Institute (5R03CA119703-02); National Institute of Environmental Health Sciences (5P42 ES007381

Neospora caninum infection and repeated abortions in humans.

To determine whether Neospora caninum, a parasite known to cause repeated abortions and stillbirths in cattle, also causes repeated abortions in humans, we retrospectively examined serum samples of 76 women with a history of abortions for evidence of N. caninum infection. No antibodies to the parasite were detected by enzyme-linked immunosorbent assay, immunofluorescence assay, or Western blot

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

A holistic multi-methodology for sustainable renovation

A review of the barriers for building renovation has revealed a lack of methodologies, which can promote sustainability objectives and assist various stakeholders during the design stage of building renovation/retrofitting projects. The purpose of this paper is to develop a Holistic Multi-methodology for Sustainable Renovation, which aims to deal with complexity of renovation projects. It provides a framework through which to involve the different stakeholders in the design process to improve group learning and group decision-making, and hence make the building renovation design process more robust and efficient. Therefore, the paper discusses the essence of multifaceted barriers in building renovation regarding cultural changes and technological/physical changes. The outcome is a proposal for a multi-methodology framework, which is developed by introducing, evaluating and mixing methods from Soft Systems Methodologies (SSM) with Multiple Criteria Decision Making (MCDM). The potential of applying the proposed methodology in renovation projects is demonstrated through a case study