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Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma

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四川生理科学杂志 2021年第10期43卷 1816-1816页

作者： leonard B Bacharier From Monroe Carell j.. Children's Hospital at Vanderbilt Nashville (L.B.B.) Fundación CIDEA Buenos Aires (J.F.M.) Campbelltown Hospital Campbelltown NSW and Western Sydney University Sydney (C.H.K.) - both in Australia Bambino Gesù Children's Hospital IRCCS Rome (A.G.F.) Clinique Spécialisée en Allergie de la Capitale Quebec QC Canada (R.G.) Hospital Vall d'Hebron Barcelona (I.M.) Arizona Allergy and Immunology Research Gilbert (N.J.) Peninsula Research Associates Rolling Hills Estates CA (L.D.S.) Sanofi Bridgewater NJ (X.M. U.K. P.J.R. E.L.) Sanofi Beijing (D.L.) Regeneron Pharmaceuticals Tarrytown NY (Y.Z. F.A.K. Y.D. M.R. D.M.W. G.D.Y. N.A. D.J.L.) Sanofi Chilly-Mazarin France (A.H.K. L.P.M.) and Sanofi Genzyme Cambridge MA (N.P. M.H.).

Background:Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standardof-care *** monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory ***:In this 52-week phase 3,randomized,double-blind,placebo-controlled trial,we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous inj.ction of dupilumab(at a dose of 100 mg for those weighing≤30 kg and 200 mg for those weighing>30 kg)or matched placebo every 2 *** the children continued to receive a stable dose of standard background *** primary end point was the annualized rate of severe asthma *** end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second(ppFEV1)at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered(ACQ-7-IA)at week *** points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype(≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of≥20 ppb at baseline)or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.

关键词： millimeter cubic continued

Comparison of novel tools with traditional cognitive tests in detecting delirium in elderly medical patients

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World j.urnal of Psychiatry 2020年第4期10卷 46-58页

作者： David j.Meagher Henry O’Connell Maeve leonard Olugbenga Williams Fahad Awan Chris Exton Michael Tenorio Margaret O’Connor Colum P Dunne Walter Cullen j.hn McFarland Dimitrios Adamis Cognitive Impairment Research Group Graduate Entry Medical SchoolUniversity of LimerickLimerick V94 YVHOIreland Department of Computer Sciences University of LimerickLimerick V94 YVHOIreland School of Medicine University College DublinDublin 4 D04 V1W8Ireland Sligo Mental Health Services BallytivanSligo F91 CD34Ireland

BACKGROUND Efficient detection of delirium and comorbid delirium-dementia is a key diagnostic *** of new,efficient delirium-focused methods of cognitive assessment is a key challenge for improved detection of neurocognitive disorders in everyday clinical *** To compare the accuracy of two novel bedside tests of attention,vigilance and visuospatial function with conventional bedside cognitive tests in identifying delirium in older hospitalized *** 180 consecutive elderly medical inpatients(mean age 79.6±7.2;51%female)referred to a psychiatry for later life consultation-liaison service with delirium,dementia,comorbid delirium-dementia and cognitively intact *** were assessed cross-sectionally with conventional bedside cognitive tests[WORLD,Months Backward test(MBT),Spatial span,Vigilance A and B,Clock Drawing test and Interlocking Pentagons test]and two novel cognitive tests[Lighthouse test,Letter and Shape Drawing test(LSD)-4].RESULTS Neurocognitive diagnoses were delirium(n=44),dementia(n=30),comorbid delirium-dementia(n=60)and no neurocognitive disorder(n=46).All conventional tests had sensitivity of>70%for delirium,with best overall accuracy for the Vigilance-B(78.3%),Vigilance-A(77.8%)and MBT(76.7%)*** sustained attention component of the Lighthouse test was the most distinguishing of delirium(sensitivity 84.6%;overall accuracy 75.6%).The LSD-4 had sensitivity of 74.0%and overall accuracy 74.4%for delirium *** tests allowed for enhanced sensitivity(>90%)and overall accuracy(≥75%)with the highest overall accuracy for the combination of MBT-Vigilance A and the combined Vigilance A and B tests(both 78.3%).When analyses were repeated for those with dementia,there were similar findings with the MBTVigilance A the most accurate overall combination(80.0%).Combining the Lighthouse-SA with the LSD-4,a fail in either test had sensitivity for delirium of 91.4 with overall accuracy of 74.4%.

关键词： Visuospatial function Attention Vigilance Letter and Shape Drawing test Lighthouse test Delirium Dementia Phenomenology Assessment

Paradigm shift in gastrointestinal surgery−combating sarcopenia with prehabilitation:Multimodal review of clinical and scientific data

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World j.urnal of Gastrointestinal Surgery 2021年第8期13卷 734-755页

作者： Frederick H Koh j.son MW Chua j.selyn Lj.Tan Fung-j.on Foo Winson j.Tan Sharmini S Sivaraj.h leonard Ming Li Ho Bin-Tean Teh Min-Hoe Chew Division of Surgery Sengkang General HospitalSingapore 544886Singapore Institute of Molecular and Cell Biology Agency for Science Technology and ResearchSingapore 138673Singapore Duke-NUS Graduate Medical School National Cancer Centre SingaporeSingapore 169610Singapore

A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and *** included an increased risk of total complications,maj.r complications,re-admissions,infections,severe infections,30 d mortality,longer hospital stay and increased hospitalization expenditures.A program to enhance recovery after surgery was meant to address these complications;however,compliance to the program since its introduction has been less than *** the last decade,the concept of prehabilitation,or"pre-surgery rehabilitation",has been *** presurgical period represents a window of opportunity to boost and optimize the health of an individual,providing a compensatory"buffer"for the imminent reduction in physiological reserve *** results have been *** review the literature to critically review the utility of prehabilitation,not j.st in the clinical realm,but also in the scientific realm,with a resource management point-of-view.

关键词： Sarcopenia Prehabilitation Surgery Frailty Value Gastrointestinal surgery

On Atmospheric-Oceanic-Land Temperature Variability and Trends

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International j.urnal of Geosciences 2013年第2期4卷 417-443页

作者： leonard j. Pietrafesa David A. Dickey Paul T. Gayes Tingzhuang Yan j.mes M. Epps Maura Hagan Shaowu Bao Machuan Peng Center for Marine & Wetland Studies Coastal Carolina University Conway South Carolina USA Department of Statistics North Carolina State University Raleigh North Carolina USA National Center for Atmospheric Research Boulder Calorado USA National Oceanic & Atmospheric Administration Silver Spring Maryland USA University of Colorado Boulder Calorado USA

The reported overall rise in global surface temperatures since the latter 19th Century is viewed largely as an atmospheric phenomena. However, we show that the global ocean is an important component in determining global surface temperatures. Via an empirical, mathematical methodology, we reveal the intrinsic modes of variability of planetary temperatures over the past 160 years, and find periods of cooling and warming, with multiple modes of variability;seasonal, inter-annual, decadal, multi-decadal and an overall warming trend. Our calculated overall rate of warming differs significantly from the estimate of the Intergovernmental Program on Climate Change, as well as the Nongovernmental Panel on Climate Change. We also investigate the modes of variability of recognized climate factors, and find a previously unreported 140 year cycle in two climate system data sets. A relatively large amplitude 60 - 70 year cycle mode appears in all of the climate factors, and may be related to the time scale of the oceanic Meridional Overturning Circulation. This and other oceanic features may modulate global surface temperatures. An empirical relationship between fossil fuel burning and the global surface temperature anomaly time series overall trend emerges from our reduction of the non-stationary, non-linear data.

关键词： Climate and Climate Factors Global Surface Temperature Anomalies Ocean Atmosphere

On the Hybrid Model of Nerve Pulse: Mathematical Analysis and Numerical Results

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j.urnal of Applied Mathematics and Physics 2023年第8期11卷 2373-2396页

作者： Alexander Mengnj. j.ke leonard Nkeck Department of Mathematics Faculty of Science University of Buea Buea Cameroon

Amongst the important phenomena in neurophysiology, nerve pulse generation and propagation is fundamental. Scientists have studied this phenomena using mathematical models based on experimental observations on the physiological processes in the nerve cell. Widely used models include: the Hodgkin-Huxley (H-H) model, which is based entirely on the electrical activity of the nerve cell;and the Heimburg and j.ckson (H-j., model based on the thermodynamic activity of the nerve cell. These classes of models do not, individually, give a complete picture of the processes that lead to nerve pulse generation and propagation. Recently, a hybrid model proposed by Mengnj., Dikandé and Ngwa (M-D-N), takes into consideration both the electrical and thermodynamic activities of the nerve cell. In their work, the first three bound states of the model are analytically computed and they showed great resemblance to some of the experimentally observed pulse profiles. With these bound states, the M-D-N model reduces to an initial value problem of a linear parabolic partial differential equation with variable coefficients. In this work we consider the resulting initial value problem and, using the theory of function spaces, propose and prove conditions under which such equations will admit unique solutions. We then verify that the resulting initial value problem from the M-D-N model satisfies these conditions and so has a unique solution. Given that the derived initial value problem is complex and there are no known analytic techniques that can be deployed to obtain its solution, we designed a numerical experiment to estimate the solutions. The simulations revealed that the unique solution is a stable pulse that propagates in the x-t plane with constant velocity and maintains the shape of the initial profile.

关键词： Nerve Impulse Nerve Pulse Propagation Hodgkin-Huxley Equation Korteweg-de Vries Equation Heimburg j.ckson Model Neurophysiology

Electron Micrographic Representations of Mechanisms of Action of Murine Norovirus on ATCC TIB-71 Cells and Level of Gene Expression

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Advances in Microbiology 2023年第1期13卷 32-47页

作者： Uchenna B. Iloghalu Sara E. Miller Akamu j. Ewunkem j.nak R. Khatiwada Shurrita S. Davis leonard L. Williams Department of Biology North Carolina A&T State University Greensboro USA Department of Biology Guilford College Greensboro USA Department of Pathology Duke University Durham USA Department of Biological Sciences Winston-Salem State University Winston-Salem USA Center for Excellence in Post-Harvest Technologies Kannapolis North Carolina A&T State University Greensboro USA

Human noroviruses (HuNoV) are the number one cause of viral gastroenteritis worldwide resulting in a significant cause of morbidity and mortality in all age groups. However, despite the medical relevance of HuNoV, effective treatment against norovirus infection is yet to be developed. In this study, we investigated the anti-Noroviral activity of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) seeds using murine norovirus, a surrogate of human norovirus. The antiviral mechanisms of action were also examined using a gene expression studies and transmission electron microscopy. Our results showed that virus-infected cells were left potentially void of all the cell machineries whereas uninfected cells represent healthy normal and dividing cells. The infected treated cells with extracts showed restoration of the dense cytoplasm, cytoplasmic membrane, and the nucleus. These cells were also associated with the expression of ORF genes. This study demonstrates the antiviral properties of Hibiscus sabdariffa (HS) calyces and Zanthoxylum armatum (ZA) and thus indicates their potential as natural remedies to treat noroviruses.

关键词： Norovirus Plant Extracts Transmission Electron Microscope Prevention/Control

Some Remarks on the Meaning and Use of the Tibetan Word bam po

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Some Remarks on the Meaning and Use of the Tibetan Word bam ...

A Case Study in the Use of Capsaicin in the Treatment of Neuropathic Chest Wall Pain and Post-thoracotomy Intercostal Neuralgia

作者： leonard W.j.van der Kuij. LIU Cuilan Department of Sanskrit and Indian Studies Harvard University

This essay seeks to ascertain the various meanings of the word barn po and is mainly a contribution to its lexicography.A study of several treatises in which it occurs suggests that it,and its subordinate unit the shl... 详细信息

关键词： bam po shlo ka Catalog Abhisamayalamkara Lha Bla ma Ye shes’od Nyang ral Nyi ma’od zer Bu ston Rin chen grub Nya dbon Kun dga’dpal Gsermdog Pan chen Shakya mchog Idan.

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Open j.urnal of Anesthesiology 2012年第4期2卷 99-101页

作者： Charles Roberts leonard Morgan Kanisha Hall Prashant Kumar Stacy j.Smith Department of Anesthesiology and Interventional Pain LSU Health Science Center School of MedicineShreveportUSA

Off label use of Quetenza? (capsaicin 8%) patch in relieving post-thoracotomy neuropathic pain proved temporarily effective, but to a degree indicating limited usefulness in a clinical setting.A 57 year-old male with chronic post-thoracotomy pain was treated with 8% capsaicin topically. Pre-procedure pain was rated as 8 on a 10 point scale, the 30 minute post procedure pain was reported as 2 - 3 on a 10 point scale. Neuralgia was completely resolved for the initial 48 hours post-procedure, then returned gradually over the next 5 days. Because pain transmission pathways are the same in post herpetic and post traumatic neuralgias, the use of 8% capsaicin merits additional study.

关键词： Post-thoracotomy Neuralgia Capsaicin Qutenza^(█)

In vitro evaluation of a new resilient, hard-carbon, thin-film coating as a bearing material for ventricular assist devices ——In Vitro Bearing Evaluation of BioMedFlex

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j.urnal of Biomedical Science and Engineering 2010年第5期3卷 525-528页

作者： Nicole A. Mielke Alex L. Massiello David j. Horvath Stephen M. Benefit Darren Burgess leonard A. R. Golding Kiyotaka Fukamachi 不详

Our aim was to evaluate the potential use of BioMedFlex? (BMF), a new resilient, hard-carbon, thin- film coating, as a blood j.urnal bearing material in Cleveland Heart’s continuous-flow left and right ven- tricular assist devices (VADs). BMF is not classified as a diamond-like carbon (DLC) and differs from other thin-film carbon coatings by its high flexural strength, radiopacity, and wear resistance. A 2- to 4-μm-thick BMF adhesion layer was deposited on the VAD j.urnal bearing surfaces. A commercial DLC coating used in other clinical blood pump applications was used as a control. Durability and reliability of the BMF coating was verified in severe pump start/stop testing using 20 BMF-coated j.urnal bearing pairs. The BMF-coated surfaces showed no coating failures, whereas 57% of the DLC bearing pairs developed scratches through the carbon coating, documenting that BMF can provide a durable coating in our blood j.urnal bearing application. In conclusion, BMF has shown qualities that support its significant advantages as an alternative j.urnal bea- ring material in Cleveland Heart pumps. Our plan includes biocompatibility testing with ongoing animal studies, endurance testing with submerged pumps running in saline, and assessment of batch coating processing capability.

关键词： Heart Assist Device Diamond-Like Carbon Materials Testing Wear Resistance j.urnal Bearing