A Systematic Review of Studies Comparing the Measurement Properties of the Three-Level and Five-Level Versions of the EQ-5D

Background: Since the introduction of the five-level version of the EQ-5D (5L), many studies have comparatively investigated the measurement properties of the original three-level version (3L) with the 5L version. Objective: The aim of this study was to consolidate the available evidence on the performance of both instruments. Methods: A systematic literature search of studies in the English and German languages was conducted (2007–January 2018) using the PubMed, EMBASE, and PsycINFO (EBSCO) databases, as well as the EuroQol Research Foundation website. Data were extracted and assessed on missing values, distributional properties, informativity indices (Shannon’s H′ and J′), inconsistencies, responsiveness, and test–retest reliability. Results: Twenty-four studies were included in the review. Missing values and floor effects (percentage reporting the worst health state) were found to be negligible for both 3L and 5L (< 5%). From 18 studies, inconsistencies ranged from 0 to 10.6%, although they were generally well below 5%, with 9 studies reporting the most inconsistencies for Usual Activities (mean percentage 4.1%). Shannon’s indices were always higher for 5L than for 3L, and all but three studies reported lower ceiling effects (‘11111’) for 5L than for 3L. There is mixed and insufficient evidence on responsiveness and test–retest reliability, although results on index values showed better performance for 5L on test–retest reliability. Conclusion: Overall, studies showed similar or better measurement properties of the 5L compared with the 3L, and evidence indicated moderately better distributional parameters and substantial improvement in informativity for the 5L compared with the 3L. Insufficient evidence on responsiveness and test–retest reliability implies further research is needed

Deformations of quantum field theories on spacetimes with Killing vector fields

The recent construction and analysis of deformations of quantum field theories by warped convolutions is extended to a class of curved spacetimes. These spacetimes carry a family of wedge-like regions which share the essential causal properties of the Poincare transforms of the Rindler wedge in Minkowski space. In the setting of deformed quantum field theories, they play the role of typical localization regions of quantum fields and observables. As a concrete example of such a procedure, the deformation of the free Dirac field is studied.Comment: 35 pages, 3 figure

Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.

Study Design: Systematic literature review. Objectives: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis. Methods: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most common presenting symptoms, incidence of pre- and postoperative neurologic deficits, associated comorbidities, infectious pathogens, approach for surgery when performed, and duration of hospitalization. Outcomes data, including return to work status, resolution of back pain, and functional recovery were also pooled among all studies and surgery-specific studies alone. Meta-analysis of studies with subgroup analysis of pain-free outcome in surgical and medical patients was performed. Results: Fifty of 1286 studies were included, comprising 4173 patients undergoing either medical treatment alone or in combination with surgery. Back pain was the most common presenting symptom, reported in 91% of patients. Neurologic deficit was noted in 31% of patients. Conclusion: Medical management remains first-line treatment of infectious pyogenic spondylodiscitis. Surgery may be indicated for progressive pain, persistent infection on imaging, deformity or neurologic deficits. If surgery is required, reported literature shows potential for significant pain reduction, improved neurologic function and a high number of patients returning to a normal functional/work status

Salvage decision-making based on carbon following an eastern spruce budworm outbreak

Forest disturbances, such as an eastern spruce budworm (Choristoneura fumiferana) outbreak, impact the strength and persistence of forest carbon sinks. Salvage harvests are a typical management response to widespread tree mortality, but the decision to salvage mortality has large implications for the fate of carbon stocks (including forest carbon and harvested wood products) in the near and long terms. In this study, we created decision-support models for salvage harvesting based on carbon after an eastern spruce budworm outbreak. We used lasso regression to determine which stand characteristics (e.g., basal area) are the best predictors of carbon 40 years after an outbreak in both salvage and no salvage scenarios. We modeled carbon at year 40 for different treatment scenarios and discount rates. Treatment scenarios represent residual stand conditions that may be present when an outbreak occurs. Economic discount rates were applied to 40-year carbon values to account for near and long-term carbon storage aspects. We found that the volume and size of eastern spruce budworm host species are significant predictors of salvage preference based on carbon. We found overall that salvaging less volume is recommended to avoid major swings in carbon budgets and that discounting carbon values to apply weight to near or long-term sequestration greatly affects whether salvaging is preferred. Lasso models are constructed for the northeastern US, however, similar concepts may be applied beyond our study area and potentially for other insect outbreaks similar to spruce budworm, such as mountain pine beetle (Dendroctonus ponderosae) or hemlock woolly adelgid (Adelges tsugae). From a policy standpoint widespread salvaging could create a large carbon emissions deficit with the risk of not being fully replenished within a desired timeframe. Since salvaging is often financially driven, especially for private landowners, carbon market payments or incentives for not salvaging is a consideration for future policy

Lumpability Abstractions of Rule-based Systems

The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a mathematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the combinatorial complexity by quotienting the reachable set of molecular species, into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper we prove that this quotienting yields a sufficient condition for weak lumpability and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system. We illustrate the framework on a case study of the EGF/insulin receptor crosstalk.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Psychometric properties of the EQ-5D-5L: a systematic review of the literature

Purpose: Although the EQ-5D has a long history of use in a wide range of populations, the newer five-level version (EQ-5D-5L) has not yet had such extensive experience. This systematic review summarizes the available published scientific evidence on the psychometric properties of the EQ-5D-5L. Methods: Pre-determined key words and exclusion criteria were used to systematically search publications from 2011 to 2019. Information on study characteristics and psychometric properties were extracted: specifically, EQ-5D-5L distribution (including ceiling and floor), missing values, reliability (test–retest), validity (convergent, known-groups, discriminate) and responsiveness (distribution, anchor-based). EQ-5D-5L index value means, ceiling and correlation coefficients (convergent validity) were pooled across the studies using random-effects models. Results: Of the 889 identified publications, 99 were included for review, representing 32 countries. Musculoskeletal/orthopedic problems and cancer (n = 8 each) were most often studied. Most papers found missing values (17 of 17 papers) and floor effects (43 of 48 papers) to be unproblematic. While the index was found to be reliable (9 of 9 papers), individual dimensions exhibited instability over time. Index values and dimensions demonstrated moderate to strong correlations with global health measures, other multi-attribute utility instruments, physical/functional health, pain, activities of daily living, and clinical/biological measures. The instrument was not correlated with life satisfaction and cognition/communication measures. Responsiveness was addressed by 15 studies, finding moderate effect sizes when confined to studied subgroups with improvements in health. Conclusions: The EQ-5D-5L exhibits excellent psychometric properties across a broad range of populations, conditions and settings. Rigorous exploration of its responsiveness is needed

Low expression of galectin-3 is associated with poor survival in node-positive breast cancers and mesenchymal phenotype in breast cancer stem cells

Background Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. Method To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. Results Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. Conclusions Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

Direct Measurement of the Top Quark Mass at D0

We determine the top quark mass m_t using t-tbar pairs produced in the D0 detector by \sqrt{s} = 1.8 TeV p-pbar collisions in a 125 pb^-1 exposure at the Fermilab Tevatron. We make a two constraint fit to m_t in t-tbar -> b W^+bbar W^- final states with one W boson decaying to q-qbar and the other to e-nu or mu-nu. Likelihood fits to the data yield m_t(l+jets) = 173.3 +- 5.6 (stat) +- 5.5 (syst) GeV/c^2. When this result is combined with an analysis of events in which both W bosons decay into leptons, we obtain m_t = 172.1 +- 5.2 (stat) +- 4.9 (syst) GeV/c^2. An alternate analysis, using three constraint fits to fixed top quark masses, gives m_t(l+jets) = 176.0 +- 7.9 (stat) +- 4.8 (syst) GeV/C^2, consistent with the above result. Studies of kinematic distributions of the top quark candidates are also presented.Comment: 43 pages, 53 figures, 33 tables. RevTeX. Submitted to Phys. Rev.