Interpreting Patient-Reported Outcome Measures: Narrative and the "Fusion of Horizons"

Patient-reported outcome measures (PROMs) are valued in healthcare evaluation for bringing patient perspectives forward, and enabling patient-centered care. The range of evidence permitted by PROMs to measure patients’ quality of life narrowly denies subjective experience. This neglect is rooted in the epistemic assumptions that ground PROMs, and the tension between the standardization (the task of measurement) and the individual and unique circumstances of patients. To counter the resulting methodological shortcomings, this article proposes a hermeutical approach and interpretive phenomenology instead of generic qualitative research methods

Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis

Background:Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective:To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and post-synaptic acetylcholine receptors (AchR) by α-bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200μl ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with α-bungarotoxin in gastrocnemius muscle. Results:Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions:Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS

Factors associated with psychological and behavioral functioning in people with type 2 diabetes living in France

<p>Abstract</p> <p>Background</p> <p>To identify demographic and clinical factors associated with psychological and behavioral functioning (PBF) in people with type 2 diabetes living in France.</p> <p>Methods</p> <p>In March 2002, approximately 10,000 adults, who had been reimbursed for at least one hypoglycemic treatment or insulin dose during the last quarter of 2001, received a questionnaire about their health status and PBF (3,646 responders). For this analysis, the 3,090 persons with type 2 diabetes, aged 18-85 years old were selected.</p> <p>PBF was measured with the adapted version of the Diabetes Health Profile for people with type 2 diabetes. This permitted the calculation of three functional scores - psychological distress (PD), barriers to activity (BA), and disinhibited eating (DE) - from 0 (worst) to 100 (best).</p> <p>Results</p> <p>Major negative associations were observed with PBF for microvascular complications (a difference of 6.7 in the BA score between persons with and without microvascular complications) and severe hypoglycemia (difference of 7.9 in the BA score), insulin treatment (-8.5 & -9.5 in the PD & BA scores respectively, as compared to treatment with oral hypoglycemic agents), non-adherence to treatment (-12.3 in the DE score for persons forgetting their weekly treatment), increasing weight (-8.5 & -9.7 in the PD & DE scores respectively, as compared to stable weight), at least one psychiatrist visit in 2001 (-8.9 in the DE score), and universal medical insurance coverage (-7.9 in the PD score) (due to low income).</p> <p>Conclusion</p> <p>Prevention and management of microvascular complications or adherence to treatment (modifiable factors) could be essential to preserving or improving PBF among people with type 2 diabetes. A specific approach to type 2 diabetes management may be required in groups with a low socioeconomic profile (particularly people with universal medical insurance coverage), or other non modifiable factors.</p

Exo-C: a probe-scale space observatory for direct imaging and spectroscopy of extrasolar planetary systems

"Exo-C" is NASAs first community study of a modest aperture space telescope mission that is optimized for high contrast observations of exoplanetary systems. The mission will be capable of taking optical spectra of nearby exoplanets in reflected light, discovering previously undetected planets, and imaging structure in a large sample of circumstellar disks. It will obtain unique science results on planets down to super-Earth sizes and serve as a technology pathfinder toward an eventual flagship-class mission to find and characterize habitable Earth-like exoplanets. We present the mission/payload design and highlight steps to reduce mission cost/risk relative to previous mission concepts. Key elements are an unobscured telescope aperture, an internal coronagraph with deformable mirrors for precise wavefront control, and an orbit and observatory design chosen for high thermal stability. Exo-C has a similar telescope aperture, orbit, lifetime, and spacecraft bus requirements to the highly successful Kepler mission (which is our cost reference). Much of the needed technology development is being pursued under the WFIRST coronagraph study and would support a mission start in 2017, should NASA decide to proceed. This paper summarizes the study final report completed in March 2015.United States. National Aeronautics and Space Administration. Astrophysics Divisio

Exo-C: a probe-scale space observatory for direct imaging and spectroscopy of extrasolar planetary systems

"Exo-C" is NASAs first community study of a modest aperture space telescope mission that is optimized for high contrast observations of exoplanetary systems. The mission will be capable of taking optical spectra of nearby exoplanets in reflected light, discovering previously undetected planets, and imaging structure in a large sample of circumstellar disks. It will obtain unique science results on planets down to super-Earth sizes and serve as a technology pathfinder toward an eventual flagship-class mission to find and characterize habitable Earth-like exoplanets. We present the mission/payload design and highlight steps to reduce mission cost/risk relative to previous mission concepts. Key elements are an unobscured telescope aperture, an internal coronagraph with deformable mirrors for precise wavefront control, and an orbit and observatory design chosen for high thermal stability. Exo-C has a similar telescope aperture, orbit, lifetime, and spacecraft bus requirements to the highly successful Kepler mission (which is our cost reference). Much of the needed technology development is being pursued under the WFIRST coronagraph study and would support a mission start in 2017, should NASA decide to proceed. This paper summarizes the study final report completed in March 2015

Trans-Species Polymorphism and Selection in the MHC Class II DRA Genes of Domestic Sheep

Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the induction of protective immunity

MEDEAS: a new modeling framework integrating global biophysical and socioeconomic constraints

Producción CientíficaA diversity of integrated assessment models (IAMs) coexists due to the different approaches developed to deal with the complex interactions, high uncertainties and knowledge gaps within the environment and human societies. This paper describes the open-source MEDEAS modeling framework, which has been developed with the aim of informing decision-making to achieve the transition to sustainable energy systems with a focus on biophysical, economic, social and technological restrictions and tackling some of the limitations identified in the current IAMs. MEDEAS models include the following relevant characteristics: representation of biophysical constraints to energy availability; modeling of the mineral and energy investments for the energy transition, allowing a dynamic assessment of the potential mineral scarcities and computation of the net energy available to society; consistent representation of climate change damages with climate assessments by natural scientists; integration of detailed sectoral economic structure (input–output analysis) within a system dynamics approach; energy shifts driven by physical scarcity; and a rich set of socioeconomic and environmental impact indicators. The potentialities and novel insights that this framework brings are illustrated by the simulation of four variants of current trends with the MEDEAS-world model: the consideration of alternative plausible assumptions and methods, combined with the feedback-rich structure of the model, reveal dynamics and implications absent in classical models. Our results suggest that the continuation of current trends will drive significant biophysical scarcities and impacts which will most likely derive in regionalization (priority to security concerns and trade barriers), conflict, and ultimately, a severe global crisis which may lead to the collapse of our modern civilization. Despite depicting a much more worrying future than conventional projections of current trends, we however believe it is a more realistic counterfactual scenario that will allow the design of improved alternative sustainable pathways in future work.Ministerio de Economía, Industria y Competitividad (Project CO2017-85110-R)Ministerio de Economía, Industria y Competitividad (Project JCI-2016–28833)MEDEAS project, funded by the European Union’s Horizon2020 research and innovation programme under grant agree-ment no. 691287.LOCOMOTION project, funded by the EuropeanUnion’s Horizon 2020 research and innovation programmeunder grant agreement no. 82110

Exo-C: a probe-scale space observatory for direct imaging and spectroscopy of extrasolar planetary systems

"Exo-C" is NASAs first community study of a modest aperture space telescope mission that is optimized for high contrast observations of exoplanetary systems. The mission will be capable of taking optical spectra of nearby exoplanets in reflected light, discovering previously undetected planets, and imaging structure in a large sample of circumstellar disks. It will obtain unique science results on planets down to super-Earth sizes and serve as a technology pathfinder toward an eventual flagship-class mission to find and characterize habitable Earth-like exoplanets. We present the mission/payload design and highlight steps to reduce mission cost/risk relative to previous mission concepts. Key elements are an unobscured telescope aperture, an internal coronagraph with deformable mirrors for precise wavefront control, and an orbit and observatory design chosen for high thermal stability. Exo-C has a similar telescope aperture, orbit, lifetime, and spacecraft bus requirements to the highly successful Kepler mission (which is our cost reference). Much of the needed technology development is being pursued under the WFIRST coronagraph study and would support a mission start in 2017, should NASA decide to proceed. This paper summarizes the study final report completed in March 2015

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer