Comparative responsiveness and minimally important difference of Fatigue Symptom Inventory (FSI) scales and the FSI-3 in trials with cancer survivors

Background Fatigue is a highly prevalent and disabling symptom in cancer survivors. Although many measures have been developed to assess survivors’ fatigue, their ability to accurately capture change following intervention has rarely been assessed in post-treatment survivors. Ultra-brief fatigue measures are preferable in clinical practice but have limited evidence supporting their use with cancer survivors. We examined the psychometric properties of four Fatigue Symptom Inventory (FSI) measures, including the new FSI-3, in cancer survivors. Examined properties included responsiveness to change and minimally important differences (MIDs). Methods We analyzed data from three randomized controlled trials with post-treatment cancer survivors (N = 328). Responsiveness to change was evaluated by comparing standardized response means for survivors who reported their fatigue as being better, the same, or worse at 2–3 months. Responsiveness to intervention was assessed via effect sizes, and MIDs were estimated by using several methods. We also computed area under the curve (AUC) values to assess FSI measures’ discriminative accuracy compared to an established cut-point. Results All FSI measures differentiated survivors who reported improvement at 2–3 months from those with stable fatigue, but did not uniformly differentiate worsening fatigue from stable fatigue. Measures showed similar levels of responsiveness to intervention, and MIDs ranged from 0.29 to 2.20 across FSI measures. AUC analyses supported the measures’ ability to detect significant fatigue. Conclusions Four FSI scales show similar responsiveness to change, and estimated MIDs can inform assessment of meaningful change in fatigue. The FSI-3 shows promise as an ultra-brief fatigue measure for survivors

A nonhuman primate model of inherited retinal disease.

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general

A new locality with ctenochasmatid pterosaurs (Pterosauria: Pterodactyloidea) in the Atacama Desert, Northern Chile

We describe a new locality with ctenochasmatid pterosaurs found in a tidal estuarine paleoenvironment of the Quebrada Monardes Formation (Lower Cretaceous). The new locality, which is named “Cerro Tormento”, is in Cerros Bravos in the northeast Atacama region, Northern Chile. Here, we describe four cervical vertebrae, one of them belonging to a small individual, the impression of a right scapulocoracoid, a left coracoid, an impression of a left humerus, an incomplete left humerus, a distal fragment of the right humerus, and impressions of a left femur and tibiotarsus. The presence of three humeri and a cervical vertebra belonging to a small pterosaur indicate that these materials represent more than one individual. The cervical vertebrae present diagnostic traits shared with ctenochasmatid pterosaurs, such as elongated vertebral centra, with integrated neural arch, low neural spines, and dorsally located neural canal. It is currently not possible to determine if there are one or more species represented. This finding is the second geographic occurrence of pterosaurs of the clade Ctenochasmatidae in the Atacama region, although it is currently uncertain if ctenochasmatids from both locations were contemporaneous. This suggests that the clade Ctenochasmatidae was widespread in what is now northern Chile. In addition, the presence of bones belonging to more than one individual preserved in Cerro Tormento suggest that pterosaur colonies were present at the southwestern margin of Gondwana during the Early Cretaceous.Fil: Alarcón Muñoz, Jhonatan Andrés. Universidad de Chile. Facultad de Ciencias Físicas y Matemáticas. Departamento de Geología; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Codorniú, Laura. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Departamento de Geología; ArgentinaFil: González, Edwin. Servicio Nacional de Geología y Minería; ChileFil: Suárez, Mario E.. Atacama Fosil Research; ChileFil: Suárez, Manuel. Universidad Andrés Bello; ChileFil: Vicencio Campos, Omar. Atacama Fosil Research; ChileFil: Soto Acuña, Sergio. Universidad de Chile. Facultad de Ciencias Físicas y Matemáticas. Departamento de Geología; ChileFil: Kaluza, Jonatan Ezequiel. Fundación de Historia Natural Félix de Azara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vargas, Alexander O.. Universidad de Chile. Facultad de Ciencias Físicas y Matemáticas. Departamento de Geología; ChileFil: Rubilar Rogers, David. Museo Nacional de Historia Natural de Chile; Chil

Radiation-free CMR diagnostic heart catheterization in children.

BACKGROUND: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety. METHODS: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected. RESULTS: During a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested. CONCLUSIONS: Comprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02739087 registered February 17, 2016

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summar

The Helium and Carbon Isotope Characteristics of the Andean Convergent Margin

Subduction zones represent the interface between Earth’s interior (crust and mantle) and exterior (atmosphere and oceans), where carbon and other volatile elements are actively cycled between Earth reservoirs by plate tectonics. Helium is a sensitive tracer of volatile sources and can be used to deconvolute mantle and crustal sources in arcs; however it is not thought to be recycled into the mantle by subduction processes. In contrast, carbon is readily recycled, mostly in the form of carbon-rich sediments, and can thus be used to understand volatile delivery via subduction. Further, carbon is chemically-reactive and isotope fractionation can be used to determine the main processes controlling volatile movements within arc systems. Here, we report helium isotope and abundance data for 42 deeply-sourced fluid and gas samples from the Central Volcanic Zone (CVZ) and Southern Volcanic Zone (SVZ) of the Andean Convergent Margin (ACM). Data are used to assess the influence of subduction parameters (e.g., crustal thickness, subduction inputs, and convergence rate) on the composition of volatiles in surface volcanic fluid and gas emissions. He isotopes from the CVZ backarc range from 0.1 to 2.6 RA (n = 23), with the highest values in the Puna and the lowest in the Sub-Andean foreland fold-and-thrust belt. Atmosphere-corrected He isotopes from the SVZ range from 0.7 to 5.0 RA (n = 19). Taken together, these data reveal a clear southeastward increase in 3He/4He, with the highest values (in the SVZ) falling below the nominal range associated with pure upper mantle helium (8 ± 1 RA), approaching the mean He isotope value for arc gases of (5.4 ± 1.9 RA). Notably, the lowest values are found in the CVZ, suggesting more significant crustal inputs (i.e., assimilation of 4He) to the helium budget. The crustal thickness in the CVZ (up to 70 km) is significantly larger than in the SVZ, where it is just ∼40 km. We suggest that crustal thickness exerts a primary control on the extent of fluid-crust interaction, as helium and other volatiles rise through the upper plate in the ACM. We also report carbon isotopes from (n = 11) sites in the CVZ, where δ13C varies between −15.3‰ and −1.2‰ [vs. Vienna Pee Dee Belemnite (VPDB)] and CO2/3He values that vary by over two orders of magnitude (6.9 × 108–1.7 × 1011). In the SVZ, carbon isotope ratios are also reported from (n = 13) sites and vary between −17.2‰ and −4.1‰. CO2/3He values vary by over four orders of magnitude (4.7 × 107–1.7 × 1012). Low δ13C and CO2/3He values are consistent with CO2 removal (e.g., calcite precipitation and gas dissolution) in shallow hydrothermal systems. Carbon isotope fractionation modeling suggests that calcite precipitation occurs at temperatures coincident with the upper temperature limit for life (122°C), suggesting that biology may play a role in C-He systematics of arc-related volcanic fluid and gas emissions.Fil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: De Moor, J. M.. University of New Mexico; Estados Unidos. UNIVERSIDAD NACIONAL DE COSTA RICA (UNA);Fil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Aguilera, F.. Universidad Católica del Norte; ChileFil: Hudak, M. R.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Turner, S. J.. University of Massachussets; Estados UnidosFil: Curtice, J.. Woods Hole Oceanographic Institution; Estados UnidosFil: Seltzer, A. M.. Woods Hole Oceanographic Institution; Estados UnidosFil: Jessen, G. L.. Universidad Austral de Chile; ChileFil: Osses, E.. Universidad Austral de Chile; ChileFil: Blamey, J. M.. Universidad de Santiago de Chile; ChileFil: Amenábar, M. J.. Universidad de Santiago de Chile; ChileFil: Selci, M.. University Of Naples Federico Ii; ItaliaFil: Cascone, M.. University Of Naples Federico Ii; ItaliaFil: Bastianoni, A.. University Of Naples Federico Ii; ItaliaFil: Nakagawa, M.. Tokyo Institute Of Technology; JapónFil: Filipovich, Ruben Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bustos, Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Buongiorno, J.. Maryville College; Estados UnidosFil: Ramírez, C. J.. Servicio Geológico Ambiental (segeoam); Costa RicaFil: Rogers, T. J.. University of Tennessee; Estados UnidosFil: Lloyd, K. G.. University of Tennessee; Estados UnidosFil: Giovannelli, D.. Institute Of Marine Biological Resources And Biotechno; Itali

Mammalian end binding proteins control persistent microtubule growth

© 2009 Komarova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0. The definitive version was published in Journal of Cell Biology 184 (2009): 691-706, doi:10.1083/jcb.200807179.End binding proteins (EBs) are highly conserved core components of microtubule plus-end tracking protein networks. Here we investigated the roles of the three mammalian EBs in controlling microtubule dynamics and analyzed the domains involved. Protein depletion and rescue experiments showed that EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes. Furthermore, we demonstrated in vitro and in cells that the EB plus-end tracking behavior depends on the calponin homology domain but does not require dimer formation. In contrast, dimerization is necessary for the EB anti-catastrophe activity in cells; this explains why the EB1 dimerization domain, which disrupts native EB dimers, exhibits a dominant-negative effect. When microtubule dynamics is reconstituted with purified tubulin, EBs promote rather than inhibit catastrophes, suggesting that in cells EBs prevent catastrophes by counteracting other microtubule regulators. This probably occurs through their action on microtubule ends, because catastrophe suppression does not require the EB domains needed for binding to known EB partners.This work was supported by the Netherlands Organization for Scientifi c Research grants to A.A., by Funda ç ã o para a Ci ê ncia e a Tecnologia fellowship to S.M. Gouveia, by a FEBS fellowship to R.M. Buey, by the National Institutes of Health grant GM25062 to G.G. Borisy and by the Swiss National Science Foundation through grant 3100A0-109423 and by the National Center of Competence in Research Structural Biology program to M.O. Steinmetz

The effect of clinician-patient alliance and communication on treatment adherence in mental health care: a systematic review

Background Nonadherence to mental health treatment incurs clinical and economic burdens. The clinician-patient alliance, negotiated through clinical interaction, presents a critical intervention point. Recent medical reviews of communication and adherence behaviour exclude studies with psychiatric samples. The following examines the impact of clinician-patient alliance and communication on adherence in mental health, identifying the specific mechanisms that mobilise patient engagement. Methods In December 2010, a systematic search was conducted in Pubmed, PsychInfo, Web of Science, Cochrane Library, Embase and Cinahl and yielded 6672 titles. A secondary hand search was performed in relevant journals, grey literature and reference. Results 23 studies met the inclusion criteria for the review. The methodological quality overall was moderate. 17 studies reported positive associations with adherence, only four of which employed intervention designs. 10 studies examined the association between clinician-patient alliance and adherence. Subjective ratings of clinical communication styles and messages were assessed in 12 studies. 1 study examined the association between objectively rated communication and adherence. Meta-analysis was not possible due to heterogeneity of methods. Findings were presented as a narrative synthesis. Conclusions Clinician-patient alliance and communication are associated with more favourable patient adherence. Further research of observer rated communication would better facilitate the application of findings in clinical practice. Establishing agreement on the tasks of treatment, utilising collaborative styles of communication and discussion of treatment specifics may be important for clinicians in promoting cooperation with regimens. These findings align with those in health communication. However, the benefits of shared decision making for adherence in mental health are less conclusive than in general medicine