Showing papers by "University of Kansas published in 2016"
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
TL;DR: The optimal simulation protocol for each program has been implemented in CHARMM-GUI and is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.
Abstract: Proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find the optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order para...
2,182 citations
TL;DR: A (2016) revision to the 2010/2011 fibromyalgia criteria combines physician and questionnaire criteria, minimizes misclassification of regional pain disorders, and eliminates the previously confusing recommendation regarding diagnostic exclusions.
997 citations
Smithsonian Institution1, Sun Yat-sen University2, University of California, Berkeley3, Naturalis4, Paris-Sorbonne University5, Universidade Federal de Minas Gerais6, University of Vermont7, Federal University of Western Pará8, University of Florida9, James Cook University10, Duke University11, University of Bonn12, University of Neuchâtel13, University of Turku14, University of Alaska Fairbanks15, Missouri Botanical Garden16, National Taiwan University17, Museum of New Zealand Te Papa Tongarewa18, National University of Río Cuarto19, University of Arizona20, Council of Agriculture21, Kaohsiung Medical University22, Chongqing Normal University23, Universidade Federal de Juiz de Fora24, Nanjing Forestry University25, Iowa State University26, Complutense University of Madrid27, University of Kansas28, Denison University29, University of Zurich30
TL;DR: A modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community‐based approach, that uses monophyly as the primary criterion for the recognition of taxa, but also aims to preserve existing taxa and circumscriptions that are both widely accepted and consistent with the understanding of pteridophyte phylogeny.
Abstract: Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predic ...
971 citations
Oregon State University1, University of Florida2, University of British Columbia3, Michigan State University4, University of Ottawa5, United States Department of Energy6, University of Michigan7, United States Department of Agriculture8, Arizona State University9, University of Kansas10, Duke University11, Boise State University12, University of California, Riverside13
TL;DR: It is demonstrated that zygomycetes comprise two major clades that form a paraphyletic grade, and the phyla Mucoromycota and ZoopagomyCota are circumscribed.
Abstract: Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.
872 citations
Yasser Iturria-Medina, Roberto C. Sotero1, Paule-Joanne Toussaint, José María Mateos-Pérez +311 more•Institutions (60)
TL;DR: Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development, suggesting early memory deficit associated with the primary disease factors.
Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.
786 citations
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam +2283 more•Institutions (141)
TL;DR: Combined fits to CMS UE proton–proton data at 7TeV and to UEProton–antiproton data from the CDF experiment at lower s, are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13.
Abstract: New sets of parameters ("tunes") for the underlying-event (UE) modeling of the PYTHIA8, PYTHIA6 and HERWIG++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE data at sqrt(s) = 7 TeV and to UE data from the CDF experiment at lower sqrt(s), are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13 TeV. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan (q q-bar to Z / gamma* to lepton-antilepton + jets) observables at 7 and 8 TeV are presented, as well as predictions of MB and UE observables at 13 TeV.
686 citations
TL;DR: This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions and describes how mast cells regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification are implicated.
Abstract: Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On the other hand, mast cells have also been implicated in the pathophysiology of many diseases, including allergy, asthma, anaphylaxis, gastrointestinal disorders, many types of malignancies, and cardiovascular diseases. This review summarizes the current understanding of the role of mast cells in many pathophysiological conditions.
558 citations
TL;DR: This multicenter randomized study shows that CA of AF is superior to AMIO in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF.
Abstract: Background—Whether catheter ablation (CA) is superior to amiodarone (AMIO) for the treatment of persistent atrial fibrillation (AF) in patients with heart failure is unknown. Methods and Results—This was an open-label, randomized, parallel-group, multicenter study. Patients with persistent AF, dual-chamber implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, New York Heart Association II to III, and left ventricular ejection fraction <40% within the past 6 months were randomly assigned (1:1 ratio) to undergo CA for AF (group 1, n=102) or receive AMIO (group 2, n=101). Recurrence of AF was the primary end point. All-cause mortality and unplanned hospitalization were the secondary end points. Patients were followed up for a minimum of 24 months. At the end of follow-up, 71 (70%; 95% confidence interval, 60%–78%) patients in group 1 were recurrence free after an average of 1.4±0.6 procedures in comparison with 34 (34%; 95% confidence interval, 25%–44%) in group 2 (log-ra...
546 citations
British Geological Survey1, University of Bergen2, University of Arizona3, Geological Survey of Canada4, University of Kansas5, University of Copenhagen6, Macquarie University7, Geoscience Australia8, Texas Tech University9, University College London10, College of Charleston11, Princeton University12
TL;DR: The LA-ICP-MS U-(Th-)Pb geochronology international community has defined new standards for the determination of U-(th)-Pb ages as discussed by the authors.
Abstract: The LA-ICP-MS U-(Th-)Pb geochronology international community has defined new standards for the determination of U-(Th-)Pb ages. A new workflow defines the appropriate propagation of uncertainties for these data, identifying random and systematic components. Only data with uncertainties relating to random error should be used in weighted mean calculations of population ages; uncertainty components for systematic errors are propagated after this stage, preventing their erroneous reduction. Following this improved uncertainty propagation protocol, data can be compared at different uncertainty levels to better resolve age differences. New reference values for commonly used zircon, monazite and titanite reference materials are defined (based on ID-TIMS) after removing corrections for common lead and the effects of excess 230Th. These values more accurately reflect the material sampled during the determination of calibration factors by LA-ICP-MS analysis. Recommendations are made to graphically represent data only with uncertainty ellipses at 2s and to submit or cite validation data with sample data when submitting data for publication. New data-reporting standards are defined to help improve the peer-review process. With these improvements, LA-ICP-MS U-(Th-)Pb data can be considered more robust, accurate, better documented and quantified, directly contributing to their improved scientific interpretation.
526 citations
TL;DR: The size and shape effects of catalyst particles on catalytic activity and selectivity of reactions performed at solid-gas or solid-liquid interfaces are discussed with a purpose of establishing correlations of size- and shape-dependent chemical and structural factors of surface of a catalyst with the corresponding catalytic performances toward understanding of catalysis at a molecular level.
Abstract: Heterogeneous catalysis is one of the most important chemical processes of various industries performed on catalyst nanoparticles with different sizes or/and shapes. In the past two decades, the catalytic performances of different catalytic reactions on nanoparticles of metals and oxides with well controlled sizes or shapes have been extensively studied thanks to the spectacular advances in syntheses of nanomaterials of metals and oxides. This review discussed the size and shape effects of catalyst particles on catalytic activity and selectivity of reactions performed at solid–gas or solid–liquid interfaces with a purpose of establishing correlations of size- and shape-dependent chemical and structural factors of surface of a catalyst with the corresponding catalytic performances toward understanding of catalysis at a molecular level.
TL;DR: RevBayes is a new open-source software package based on probabilistic graphical models, a powerful generic framework for specifying and analyzing statistical models that outperforms competing software for several standard analyses and needs to explicitly specify each part of the model and analysis.
Abstract: Programs for Bayesian inference of phylogeny currently implement a unique and fixed suite of models Consequently, users of these software packages are simultaneously forced to use a number of programs for a given study, while also lacking the freedom to explore models that have not been implemented by the developers of those programs We developed a new open-source software package, RevBayes, to address these problems RevBayes is entirely based on probabilistic graphical models, a powerful generic framework for specifying and analyzing statistical models Phylogenetic-graphical models can be specified interactively in RevBayes, piece by piece, using a new succinct and intuitive language called Rev Rev is similar to the R language and the BUGS model-specification language, and should be easy to learn for most users The strength of RevBayes is the simplicity with which one can design, specify, and implement new and complex models Fortunately, this tremendous flexibility does not come at the cost of slower computation; as we demonstrate, RevBayes outperforms competing software for several standard analyses Compared with other programs, RevBayes has fewer black-box elements Users need to explicitly specify each part of the model and analysis Although this explicitness may initially be unfamiliar, we are convinced that this transparency will improve understanding of phylogenetic models in our field Moreover, it will motivate the search for improvements to existing methods by brazenly exposing the model choices that we make to critical scrutiny RevBayes is freely available at http://wwwRevBayescom [Bayesian inference; Graphical models; MCMC; statistical phylogenetics]
TL;DR: In this paper, an isotropic, unbroken power-law flux with a normalization at 100 TeV neutrino energy of (0.90 -0.27 +0.30) × 10-18 Gev-1 cm-2 s-1 sr-1 and a hard spectral index of γ = 2.13 ± 0.13.
Abstract: The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 194 TeV and 7.8 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at 5.6s significance. The data are well described by an isotropic, unbroken power-law flux with a normalization at 100 TeV neutrino energy of (0.90 -0.27 +0.30) × 10-18 Gev-1 cm-2 s-1 sr-1and a hard spectral index of γ = 2.13 ± 0.13. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest-energy event observed has a reconstructed muon energy of (4.5 ± 1.2) PeV which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known γ-ray sources was found. Using the high statistics of atmospheric neutrinos we report the current best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below 1.06 in units of the flux normalization of the model in Enberg et al.
TL;DR: A simple microfluidic approach (ExoSearch) which provides enriched preparation of blood plasma exosomes for in situ, multiplexed detection using immunomagnetic beads and provides an essentially needed platform for utilization of exosomal tumor markers in clinical cancer diagnosis, as well as fundamental exosome research.
Abstract: Tumor-derived circulating exosomes, enriched with a group of tumor antigens, have been recognized as a promising biomarker source for cancer diagnosis via a less invasive procedure. Quantitatively pinpointing exosome tumor markers is appealing, yet challenging. In this study, we developed a simple microfluidic approach (ExoSearch) which provides enriched preparation of blood plasma exosomes for in situ, multiplexed detection using immunomagnetic beads. The ExoSearch chip offers a robust, continuous-flow design for quantitative isolation and release of blood plasma exosomes in a wide range of preparation volumes (10 μL to 10 mL). We employed the ExoSearch chip for blood-based diagnosis of ovarian cancer by multiplexed measurement of three exosomal tumor markers (CA-125, EpCAM, CD24) using a training set of ovarian cancer patient plasma, which showed significant diagnostic power (a.u.c. = 1.0, p = 0.001) and was comparable with the standard Bradford assay. This work provides an essentially needed platform for utilization of exosomes in clinical cancer diagnosis, as well as fundamental exosome research.
University of California, San Francisco1, University of Chicago2, University of Pennsylvania3, Buck Institute for Research on Aging4, University of Texas MD Anderson Cancer Center5, University of Minnesota6, University of California, San Diego7, Mayo Clinic8, Loyola University Chicago9, Georgetown University10, University of Kansas11, University of Arizona12, Oregon Health & Science University13, University of Denver14, Inova Fairfax Hospital15, University of Texas Southwestern Medical Center16, University of Southern California17, Emory University18
TL;DR: The process used in the I-SPY 2 trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer.
Abstract: BackgroundThe genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. MethodsIn this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker...
Pennsylvania State University1, Oak Ridge National Laboratory2, Lawrence Berkeley National Laboratory3, Stanford University4, University of Pittsburgh5, University of Regensburg6, Columbia University7, University of Kansas8, University of Virginia9, University of Arizona10, University of Pennsylvania11, Lehigh University12, University of Chicago13, Rutgers University14, University of California, Berkeley15, Northwestern University16
TL;DR: Lin et al. as mentioned in this paper reviewed the most recent breakthrough discoveries as well as emerging opportunities and remaining challenges in the field of 2D materials, including transition metal dichalcogenides, mono-elemental 2D sheets, and several carbide-and nitride-based materials.
Abstract: Author(s): Lin, Z; McCreary, A; Briggs, N; Subramanian, S; Zhang, K; Sun, Y; Li, X; Borys, NJ; Yuan, H; Fullerton-Shirey, SK; Chernikov, A; Zhao, H; McDonnell, S; Lindenberg, AM; Xiao, K; Le Roy, BJ; Drndic, M; Hwang, JCM; Park, J; Chhowalla, M; Schaak, RE; Javey, A; Hersam, MC; Robinson, J; Terrones, M | Abstract: The rise of two-dimensional (2D) materials research took place following the isolation of graphene in 2004. These new 2D materials include transition metal dichalcogenides, mono-elemental 2D sheets, and several carbide- and nitride-based materials. The number of publications related to these emerging materials has been drastically increasing over the last five years. Thus, through this comprehensive review, we aim to discuss the most recent groundbreaking discoveries as well as emerging opportunities and remaining challenges. This review starts out by delving into the improved methods of producing these new 2D materials via controlled exfoliation, metal organic chemical vapor deposition, and wet chemical means. We look into recent studies of doping as well as the optical properties of 2D materials and their heterostructures. Recent advances towards applications of these materials in 2D electronics are also reviewed, and include the tunnel MOSFET and ways to reduce the contact resistance for fabricating high-quality devices. Finally, several unique and innovative applications recently explored are discussed as well as perspectives of this exciting and fast moving field.
TL;DR: In this paper, the authors discuss the role of nitrogen and phosphorus in the degradation of rivers and streams in many parts of the world, including the USA and Canada, and their role in this process.
Abstract: Flowing waters receive substantial nutrient inputs, including both nitrogen (N) and phosphorus (P), in many parts of the world. Eutrophication science for rivers and streams has unfortunately lagge...
University of Pittsburgh1, University of Edinburgh2, University of Birmingham3, Baylor University Medical Center4, University of California, San Francisco5, Queen Elizabeth Hospital Birmingham6, Harvard University7, Royal Prince Alfred Hospital8, Cleveland Clinic9, Oslo University Hospital10, Kyoto University11, University Health Network12, Mayo Clinic13, Mount Sinai Hospital14, Icahn School of Medicine at Mount Sinai15, University of São Paulo16, University of Cambridge17, Columbia University18, Cincinnati Children's Hospital Medical Center19, Universidade Federal do Rio Grande do Sul20, Loma Linda University21, Ain Shams University22, Hospital of the University of Pennsylvania23, University Medical Center Groningen24, Toronto General Hospital25, University of Chicago26, Beni-Suef University27, Kobe University28, Temple University29, Lahey Hospital & Medical Center30, Duke University31, University of North Carolina at Chapel Hill32, University of California, Los Angeles33, Cliniques Universitaires Saint-Luc34, Northwestern University35, St. Joseph's Hospital and Medical Center36, Sahlgrenska University Hospital37, Beth Israel Deaconess Medical Center38, University of Kansas39, Hadassah Medical Center40, University of Southern California41, University of Miami42, Dokuz Eylül University43, University of Pennsylvania44, University of Alberta Hospital45, University of Texas Medical Branch46, University of Rome Tor Vergata47, University of Patras48, Karolinska University Hospital49, Tulane University50
TL;DR: New recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization are included.
Icahn School of Medicine at Mount Sinai1, National Institutes of Health2, Bronson Methodist Hospital3, Rush University Medical Center4, University of Kansas5, University of Maryland, Baltimore6, Geisinger Health System7, Kaiser Permanente8, Baylor College of Medicine9, Augsburg College10, Stanford University11, University of Alberta12
TL;DR: The 2008 AAN guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia, headache, and adult spasticity are updated and onaBoNT-A is established as ineffective and should not be offered for episodic migraine and is probably ineffective for chronic tension-type headaches.
Abstract: Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B).
Hong Kong Polytechnic University1, Odense University Hospital2, Albert Einstein College of Medicine3, University of Texas MD Anderson Cancer Center4, University of Kansas5, University of Toronto6, Indiana University – Purdue University Indianapolis7, Martin Luther University of Halle-Wittenberg8, University of South Australia9, University of Rochester Medical Center10, Princess Margaret Cancer Centre11, Boston Children's Hospital12
TL;DR: The present research presents a novel and scalable approach that combines traditional and regenerative approaches to oncology that has real-time, real-world implications for individual patient care and quality of life.
TL;DR: It is suggested that mitochondrial targeted antioxidants can be viable therapeutic agents against hepatotoxicity induced by APAP overdose, and re-purposing existing drugs to target oxidative stress and other concurrent signaling events can be a promising strategy to increase its potential application in patients with AP AP overdose.
Abstract: Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P450-generated reactive oxygen species (ROS) during APAP metabolism, which resulted in massive lipid peroxidation and subsequent liver injury. However, subsequent studies convincingly challenged this assumption and the current paradigm suggests that mitochondria are the main source of ROS, which impair mitochondrial function and are responsible for cell signaling resulting in cell death. Although immune cells can be a source of ROS in other models, no reliable evidence exists to support a role for immune cell-derived ROS in APAP hepatotoxicity. Recent studies suggest that mitochondrial targeted antioxidants can be viable therapeutic agents against hepatotoxicity induced by APAP overdose, and re-purposing existing drugs to target oxidative stress and other concurrent signaling events can be a promising strategy to increase its potential application in patients with APAP overdose.
University College London1, Royal Melbourne Hospital2, Université de Montréal3, Universidade Federal do Rio Grande do Sul4, Emory University5, University of Parma6, Gazi University7, Boston Children's Hospital8, University of Copenhagen9, Cairo University10, University of São Paulo11, NewYork–Presbyterian Hospital12, Northwestern University13, University of Kansas14, University of Pittsburgh15, University of Zaragoza16, University of Utah17, University of Washington18, Autonomous University of Barcelona19, University of Sunderland20, University of California, San Francisco21, Amicus Therapeutics22, Baylor University Medical Center23
TL;DR: Among all randomly assigned patients with Fabry's disease (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migAlastat group and the placebo group.
Abstract: BackgroundFabry’s disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. MethodsThe initial assay of mutant α-galactosidase forms that we used to categorize 67 patients with Fabry’s disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant α-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (≥50% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-re...
TL;DR: Surgical management with complete surgical excision is essential to achieve optimal event-free survival (EFS) and OS in patients with BI-ALCL.
Abstract: PurposeBreast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach.Patients and MethodsIn this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention.ResultsThe median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule sur...
TL;DR: Serum TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography, and this effect is reversed by renal transplantation.
Abstract: Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r(2)=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8-133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1-6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min-max] 71.2 μM [29.2-189.7 μM] pretransplant versus 11.4 μM [8.9-20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.
ETH Zurich1, United States Department of Energy2, Macquarie University3, California Institute of Technology4, University of Wisconsin-Madison5, Harvard University6, United States Department of Agriculture7, Oregon University System8, University of New Mexico9, University of Kansas10, Wageningen University and Research Centre11
TL;DR: The results show that the detrimental effects of severe summer drought on ecosystem carbon storage can be mitigated by warming-induced increases in spring carbon uptake, and suggest that the positive carbon cycle effect of warm spring enhances water limitations and can increase summer heating through biosphere–atmosphere feedbacks.
Abstract: The global terrestrial carbon sink offsets one-third of the world's fossil fuel emissions, but the strength of this sink is highly sensitive to large-scale extreme events. In 2012, the contiguous United States experienced exceptionally warm temperatures and the most severe drought since the Dust Bowl era of the 1930s, resulting in substantial economic damage. It is crucial to understand the dynamics of such events because warmer temperatures and a higher prevalence of drought are projected in a changing climate. Here, we combine an extensive network of direct ecosystem flux measurements with satellite remote sensing and atmospheric inverse modeling to quantify the impact of the warmer spring and summer drought on biosphere-atmosphere carbon and water exchange in 2012. We consistently find that earlier vegetation activity increased spring carbon uptake and compensated for the reduced uptake during the summer drought, which mitigated the impact on net annual carbon uptake. The early phenological development in the Eastern Temperate Forests played a major role for the continental-scale carbon balance in 2012. The warm spring also depleted soil water resources earlier, and thus exacerbated water limitations during summer. Our results show that the detrimental effects of severe summer drought on ecosystem carbon storage can be mitigated by warming-induced increases in spring carbon uptake. However, the results also suggest that the positive carbon cycle effect of warm spring enhances water limitations and can increase summer heating through biosphere-atmosphere feedbacks.
TL;DR: This randomized study showed that both after a single procedure and after redo procedures in patients with LSPAF, empirical electrical isolation of the LAA improved long-term freedom from atrial arrhythmias without increasing complications.
University of São Paulo1, Alfred I. duPont Hospital for Children2, Robarts Research Institute3, University of Pennsylvania4, University of New South Wales5, University of Western Australia6, Boca Raton Regional Hospital7, University of Milan8, University of Amsterdam9, Masaryk University10, McGill University11, University College London12, University of Kansas13, University of the Witwatersrand14, Sultan Qaboos University15, Imperial College London16, Erasmus University Rotterdam17, Osaka University18
TL;DR: This Review aims to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment.
University of Arizona1, United States Geological Survey2, Simon Fraser University3, University of New South Wales4, University of Kansas5, University of California, Santa Barbara6, National Center for Atmospheric Research7, Goddard Space Flight Center8, University of Texas at Austin9, Colorado School of Mines10
TL;DR: In this article, an analysis of the potential impact of climate change on groundwater recharge across the western United States (west of 100° longitude) is presented synthesizing existing studies and applying current knowledge of recharge processes and amounts.
TL;DR: It is demonstrated that sagittal spino-pelvic alignment varies with age, and operative realignment targets should account for age, with younger patients requiring more rigorous alignment objectives.
Abstract: Study Design.Retrospective review of prospective, multicenter database.Objective.The aim of the study was to determine age-specific spino-pelvic parameters, to extrapolate age-specific Oswestry Disability Index (ODI) values from published Short Form (SF)-36 Physical Component Score (PCS) data, and t
TL;DR: An overview of waveform diversity is provided in this paper, from the basic principles upon which it is founded to the myriad different areas being explored in research for practical sensing applications, as well as an overview of different areas of interest.
Abstract: Radar waveform diversity has received considerable attention in recent years due to increasing spectral congestion and the burgeoning capabilities of digital waveform generation. The promise of waveform diversity is far greater utilization of available degrees of freedom to enhance sensing performance and to even facilitate new operating modes. This tutorial provides an overview of this very broad topic, from the basic principles upon which it is founded to the myriad different areas being explored in research for practical sensing applications.