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微电脑世界 1996年第9期 127-131页

作者： Bryan Hastings amy helen johnson 张缨北京9832信箱 100029

浏览器是访问Web上网点和声音的通行证。现在是否到了不用Netscape的Navigator,转而去用微软Internet Explorer的时候了?究竟谁是最棒的Web浏览器?以下将对这两种浏览器作一个全面的比较。

关键词： Internet网 WEB浏览器浏览器

Adiponectin signalling in bone homeostasis,with age and in disease

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Bone Research 2021年第1期9卷 15-25页

作者： Jonathan W.Lewis James R.Edwards amy J.Naylor helen M.McGettrick Rheumatology Research Group Institute of Inflammation and AgeingUniversity of BirminghamBirmingham B152TTUK Ageing&Regeneration Research Group Botnar Research CentreUniversity of OxfordOxford OX37LDUK

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin *** the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and *** studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of ***,human studies often demonstrate an inverse relationship between adiponectin concentration and bone ***,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional *** such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in *** this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in ***,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.

关键词： homeostasis metabolism consequences

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera Carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and Digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of Digestive Diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of Digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and Digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England

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World Journal of Gastrointestinal Oncology 2023年第12期15卷 2077-2092页

作者： Sophie Jose amy Zalin-Miller Craig Knott Lizz Paley Daniela Tataru helen Morement Mireille B Toledano Shahid A Khan Health Data Analysis Health Data Insight CICCambridge CB215XEUnited Kingdom National Disease Registration Service National Health Service EnglandLondon SE18UGUnited Kingdom Department of Executive AMMF-The Cholangiocarcinoma CharityEssex CM241QWUnited Kingdom MRC Centre for Environment and Health Imperial College LondonLondon SW72BXUnited Kingdom Mohn Centre for Children's Health and Wellbeing Imperial College LondonLondon SW72BXUnited Kingdom Liver Unit Division of Digestive DiseasesImperial College LondonLondon SW72BXUnited Kingdom

BACKGROUND Outcomes for cholangiocarcinoma(CCA)are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous *** curative surgery,which is only an option for a minority of patients diagnosed at an early stage,few systemic therapy options are currently recommended to relieve symptoms and prolong *** insertion to manage disease complications requires highly specialised *** is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA *** To assess geographic variation in treatments received amongst CCA patients in *** Data used in this cohort study were drawn from the National Cancer Registration Dataset(NCRD),Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset.A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the *** curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of *** probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis,and for socio-demographic and clinical characteristics at *** Of 8853 CCA patients,1102(12.4%)received potentially curative *** mean[95%confidence interval(CI)]percentage-point difference from the population average ranged from-3.96(-6.34 to-1.59)%to 3.77(0.54 to 6.99)%across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics,showing statistically significant *** 7751 who did not receive surgery,1542(19.9%)received systemic therapy,with mean[95%CI]percentage-point difference from the population average between-3.84(-8.04 to 0.35)%to 9.28(1.76 to 16.80)%across Cancer Alliances after adjustm

关键词： Cholangiocarcinoma Biliary tract cancer Liver cancer Treatment Surgery Systemic therapy Chemotherapy Stent England

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017

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World Journal of Gastroenterology 2023年第24期29卷 3825-3842页

作者： amy Zalin-Miller Sophie Jose Craig Knott Lizz Paley Daniela Tataru helen Morement Mireille B Toledano Shahid A Khan Department of Analytics Health Data Insight CICCambridge CB215XEUnited Kingdom Disease Registration Service NHS EnglandLondon E144PUUnited Kingdom CEO AMMFLondon CM241QWUnited Kingdom MRC Centre for Environment and Health School of Public HealthImperial College LondonLondon SW72BXUnited Kingdom Liver Unit Division of Digestive DiseasesImperial College LondonLondon W21NYUnited Kingdom

BACKGROUND Incidence of cholangiocarcinoma(CCA)is rising,with overall prognosis remaining very *** for the high mortality of CCA include its late presentation in most patients,when curative options are no longer feasible,and poor response to systemic therapies for advanced *** presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation(EP).Earlier diagnoses may be made by Two Week Wait(TWW)referrals through General practitioner(GP).We hypothesise that TWW referrals and EP routes to diagnosis differ across regions in *** To investigate routes to diagnosis of CCA over time,regional variation and influencing *** We linked patient records from the National Cancer Registration Dataset to Hospital Episode Statistics,Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in *** used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or EP across Cancer Alliances in England,adjusting for potential *** between the proportion of people diagnosed by TWW referral and EP was investigated with Spearman’s correlation *** Of 23632 patients diagnosed between 2006-2017 in England,the most common route to diagnosis was EP(49.6%).Non-TWW GP referrals accounted for 20.5%of diagnosis routes,13.8%were diagnosed by TWW referral,and the remainder 16.2%were diagnosed via an‘other’or Unknown *** proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9%to 19.8%,conversely EP diagnosis route declined,falling from 51.3%to 46.0%.Statistically significant variation in both the TWW referral and EP proportions was found across Cancer ***,presence of comorbidity and underlying liver disease were independently associated with both a lowe

关键词： Cholangiocarcinoma Route to diagnosis Two Week Wait Emergency presentation Regional variation

Dietary supplementation of Bacillus subtilis influenced intestinal health of weaned pigs experimentally infected with a pathogenic E. coli

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Journal of Animal Science and Biotechnology 2019年第4期10卷 969-980页

作者： Kwangwook Kim Yijie He Xia Xiong amy Ehrlich Xunde Li helen Raybould Edward R.Atwill Elizabeth A.Maga Jens JΦrgensen Yanhong Liu Department of Animal Science University of CaliforniaDavisCA 95616USA School of Veterinary Medicine University of CaliforniaDavisCA 95616USA Chr.Hansen A/S HoersholmDenmark

Background: There is growing evidence to support the beneficial effects of supplementing direct-fed microbials(DFM) on performance, health status, and immune responses of weaned pigs. Therefore, the objective of this study was to investigate dietary supplementation of Bacillus subtilis(DSM 25841) on growth performance, diarrhea, gut permeability and immunity of weaned pigs experimentally infected with a pathogenic F-18 Escherichia coli(E. coli).Results: The F18 E. coli infection reduced(P < 0.05) growth performance and intestinal villi height, whereas increased(P < 0.05) diarrhea and transcellular and paracellular permeability in the jejunum compared with non-challenged control. Supplementation of Bacillus subtilis linearly enhanced average daily gain of E. coli infected pigs from d 0 to 5 post-inoculation(PI)(P < 0.05) and d 0 to 11 PI(P = 0.058). Supplementation of high dose of Bacillus subtilis reduced(P < 0.05) both transcellular and paracellular permeability on d 5 and d11 PI compared with the E. coli infected pigs fed with control diet. E. coli infection up-regulated(P < 0.05)the m RNA expression of SLC5 A10(soluble carrier family 5 member 10) and MUC2(mucin 2) on d 5 PI, but down-regulated(P < 0.05) expression of SLC5 A10, MUC2, and CLDN1 on d 11 PI in jejunal mucosa when pigs were fed with the control diet. Supplementation of Bacillus subtilis linearly up-regulated(P < 0.05) the m RNA expression of CFTR and ZO1 on d 5 PI and SLC5 A10 and MUC2 on d 11 PI in jejunal mucosa of E. coli infected pigs. In addition, E. coli infection increased(P < 0.05) the m RNA expression of several immune genes(IL1 A, IL1 B, and IL7 on d 5 PI, and IL1 B, IL6, IL7, and TNF on d 11 PI) in the ileal mucosa of weaned pigs. Inclusion of Bacillus subtilis to control diet linearly down-regulated gene expression of IL1 A on d 5 PI(P = 0.07) and IL6 on d 11 PI(P < 0.05) in ileal mucosa of E. coli infected ***: Supplementation of Bacillus subtilis(DSM 25841) enhanced growth r

关键词： Bacillus subtilis Growth rate Gut barrier function Intestinal inflammation Pathogenic Escherichia coli Weaned pigs

Australian children living with rare diseases:health service use and barriers to accessing care

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World Journal of Pediatrics 2023年第7期19卷 701-709页

作者： Suzy Teutsch Yvonne Zurynski Guy DEslick Marie Deverell John Christodoulou helen Leonard Troy Dalkeith Sandra LJjohnson Elizabeth JElliott Faculty of Medicine and Health Discipline of Child and Adolescent HealthThe University of SydneySydneyNSWAustraliaAustralian Australian Paediatric Surveillance Unit Kids ResearchSydney Children's Hospitals NetworkWestmeadNSWAustralia Australian Institute of Health Innovation Center for Healthcare Resilience and Implementation Scienceand NHMRC Partnership Centre in Health System SustainabilityMacquarie UniversitySydneyNSWAustraliaFaculty of Medicine and HealthDiscipline of Child and Adolescent HealthThe University of SydneySydneyNSWAustralia Government Department of Health Western Australia PerthWAAustralia Murdoch Children's Research Institute and Victorian Clinical Genetics Services Royal Children's HospitalParkvilleVICAustralia Department of Paediatrics The University of MelbourneParkvilleVICAustralia Telethon Kids Institute The University of Western AustraliaNedlandsWAAustralia Genetic Metabolic Disorders Service Sydney Children's Hospitals NetworkWestmeadNSWAustralia

Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary *** aimed to determine health service utilization by Australian children with rare diseases and barriers to access-ing *** Parents completed an online survey on health professional and emergency department(ED)presentations,hospi-talization,and barriers to accessing *** barriers to service access included residential location(city,regional,remote)and child health-related functioning,determined using a validated,parent-completed measure-of-function *** Parents of 462 children with over 240 rare diseases completed the *** with the general population,these children were more likely to be hospitalized[odds ratio(OR)=17.25,95%confidence interval(CI)=15.50-19.20]and present to the ED(OR=4.15,95%CI=3.68-4.68)or a family physician(OR=4.14,95%CI=3.72-4.60).Child functional impairment was nil/mild(31%),moderate(48%)or severe(22%).Compared to children with nil/mild impair-ment,those with severe impairment were more likely to be hospitalized(OR=13.39,95%CI=7.65-23.44)and present to the ED(OR=11.16,95%CI=6.46-19.27).Most children(75%)lived in major cities,but children from regional(OR=2.78,95%CI=1.72-4.55)and remote areas(OR=9.09,95%CI=3.03-25.00)experienced significantly more barriers to healthcare access than children from major *** included distance to travel,out-of-pocket costs,and lack of specialist medical and other health *** Children with rare diseases,especially those with severe functional impairment have an enormous impact on health services,and better integrated multidisciplinary services with patient-centered care are *** must be improved for children living in rural and remote settings.

关键词： Access Health functioning Health service use Rare diseases

Defining strawberry shape uniformity using 3D imaging and genetic mapping

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Horticulture Research 2020年第1期7卷 1126-1138页

作者： Bo Li helen M.Cockerton Abigail Wjohnson Amanda Karlström Eleftheria Stavridou Greg Deakin Richard J.Harrison NIAB EMR East MallingKent ME196BJUK University of the West of England Bristol BS161QYUK NIAB Huntingdon RoadCambridge CB30LEUK

Strawberry shape uniformity is a complex trait,influenced by multiple genetic and environmental *** complicate matters further,the phenotypic assessment of strawberry uniformity is confounded by the difficulty of quantifying geometric parameters‘by eye’and variation between *** in-depth genetic analysis of strawberry uniformity has not been undertaken to date,due to the lack of accurate and objective ***,uniformity remains one of the most important fruit quality selection criteria for the development of a new *** this study,a 3D-imaging approach was developed to characterise berry shape *** show that circularity of the maximum circumference had the closest predictive relationship with the manual uniformity *** five or six automated metrics provided the best predictive model,indicating that human assessment of uniformity is highly ***,visual assessment of strawberry fruit quality in a multi-parental QTL mapping population has allowed the identification of genetic components controlling uniformity.A“regular shape”QTL was identified and found to be associated with three uniformity *** QTL was present across a wide array of germplasm,indicating a potential candidate for marker-assisted breeding,while the potential to implement genomic selection is explored.A greater understanding of berry uniformity has been achieved through the study of the relative impact of automated metrics on human perceived ***,the comprehensive definition of strawberry shape uniformity using 3D imaging tools has allowed precision phenotyping,which has improved the accuracy of trait quantification and unlocked the ability to accurately select for uniform berries.

关键词： straw breeding shape

Differential subcellular distribution renders HAI-2 a less effective protease inhibitor than HAI-1 in the control of extracellular matriptase proteolytic activity

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Genes & Diseases 2022年第4期9卷 1049-1061页

作者： Yi-Lin Chiu Yi-Ying Wu Robert B.Barndt Yu-Wen Lin Hou-Ping Sytwo amy Cheng Kacy Yang Khee-Siang Chan Jehng-Kang Wang Michael D.johnson Chen-Yong Lin Lombardi Comprehensive Cancer Center Department of Oncology Georgetown UniversityWashingtonDC 20057USA Department of Biochemistry National Defense Medical CenterTapei 114Chinese Taipei Division of Hematology/Oncology Department of Internal MedicineTri-Service General HospitalNational Defense Medical CenterTapei 114Chinese Taipei School of Medicine National Defense Medical CenterTapei 114Chinese Taipei Department of Intensive Care Medicine Chi Mei Medical CenterTainan 710Chinese Taipei

The integral membrane,Kunitz-type serine protease inhibitors HAI-1 and HAI-2,can suppress the proteolytic activity of the type 2 transmembrane serine protease matriptase with high specificity and *** levels of extracellular matriptase proteolytic activity have,however,been observed in some neoplastic B-cells with high levels of endogenous HAI-2,indicating that HAI-2 may be an ineffective matriptase inhibitor at the cellular *** different effectiveness of the HAIs in the control of extracellular matriptase proteolytic activity is examined *** inducing matriptase zymogen activation in the HAI Teton Daudi Burkitt lymphoma cells,which naturally express matriptase with very low levels of HAI-2 and no HAI-1,nascent active matriptase was rapidly inhibited or shed as an enzymatically active *** increasing HAI-1 expression,cellular matriptase-HAI-1 complex increased,and extracellular active matriptase decreased *** HAI-2 expression,however,resulted in cellular matriptase-HAI-2 complex levels reaching a plateau,while extracellular active matriptase remained *** contrast to this differential effect,both HAI-1 and HAI-2,even at very low levels,were shown to promote the expression and cell-surface translocation of endogenous *** difference in the suppression of extracellular active matriptase by the two closely related serine protease inhibitors could result from the primarily cell surface expression of HAI-1 compared to the mainly intracellular localization of *** HAIs,therefore,resemble one another with respect to promoting matriptase expression and surface translocation but differ in their effectiveness in the control of extracellular matriptase enzymatic activity.

关键词： HAI-1 HAI-2 Matriptase Neoplastic B-cells Proteolytic activity

Treatment Patterns and Healthcare Costs among U.S. Patients with Advanced Melanoma Initiating Subsequent Systemic Therapy Following Use of Ipilimumab (IPI)

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Journal of Cancer Therapy 2016年第5期7卷 335-343页

作者： Elisabetta Malangone-Monaco Tony Okoro Beata Korytowsky amy Stanford Stephen Johnston William johnson Sigrun Hallmeyer Truven Health Analytics Bethesda USA Bristol-Myers Squibb Princeton USA Oncology Specialists SC Park Ridge USA

As the treatment landscape for advanced melanoma continues to evolve, it is critical to focus on unmet needs and understand the cost of therapy. While Ipilimumab (IPI), an immunotherapy indicated for unresectable advanced melanoma, has been a mainstay of 1st-line treatment, there was no standard of care following progression until recently. The objective of this study was to examine real-world treatment patterns and healthcare costs following IPI use in advanced melanoma patients prior to the anti-PD-1 class approval. Adult stage III or IV melanoma patients treated with IPI were selected between April 1, 2011, and September 30, 2013, from a large U.S. commercial and Medicare claims database. Patients were evaluated for therapy after IPI, with an index date set as the first systemic therapy after IPI. Per-Patient Per-Month (PPPM) healthcare costs while on active treatment were evaluated from index until treatment discontinuation, inpatient death, end of insurance enrollment, or September 30, 2013. Of 361 eligible patients, 111 (30.7%) initiated subsequent systemic therapy (mean age, 57 years;64.9% male). The most common therapies, single-agent or combination, included vemurafenib (32.4%), paclitaxel (28.8%), temozolomide (20.7%), and carboplatin (17.1%). During a median follow-up of 130 days, mean [standard deviation] PPPM all-cause total healthcare costs were $20,383 [$18,988], of which $4800 (23.6%), $5899 (28.9%), and $9684 (47.5%) were related to melanoma drug costs, medical claims with a diagnosis of melanoma, and other (non-specified) utilization, respectively. When considering total care, the costs of U.S. patients with advanced melanoma post-IPI were substantial across all commonly used agents.

关键词： Healthcare Costs Ipilimumab Melanoma Treatment Patterns