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Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system

Asian Journal of Andrology 2018年第2期20卷 120-130页

作者： T Hugh Jones Daniel m kelly Robert Hague Centre for Diabetes and Endocrinology Barnsley Hospital NHS Foundation Trust Barnsley UK Academic Unit of Diabetes Endocrinology and Metabolism Department of Oncology and Metabolism University of Sheffield Medical School Sheffield UK Biomedical Research Centre Sheffield Hallam University Sheffield UK

Testosterone deficiency is common in men with cardiovascular disease （CVD）, and randomized placebo-controlled trials （RCTs） have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise （VO2m,x） and muscle strength in chronic heart failure （CHF）, shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade （L-calcium channel） and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO2m=x and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the

关键词： cardiovascular testosterone testosterone replacement

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management of stage Ⅳ rectal cancer: Palliative options

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World Journal of Gastroenterology 2011年第7期17卷 835-847页

作者： Sean m Ronnekleiv-kelly Gregory D Kennedy Department of Surgery Section of Colon and Rectal Surgery University of Wisconsin School of Medicine and Public Health 600 HighlandAvenue G4/701A CSC Madison WI 53792 United States

Approximately 30% of patients with rectal cancer present with metastatic disease. many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.

关键词： Palliative therapy Rectal cancer malignant bleeding malignant obstruction Endorectal stenting Laser ablation

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UV reflectance but no evidence for colour mimicry in a putative brood-deceptive orchid Corybas cheesemanii

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Current Zoology 2014年第1期60卷 104-113页

作者： m. m. kelly A. C. GASKETT School of Biological Sciences The University of Auckland Private Bag 92019 Auckland 1142 New Zealand

Rewardless orchids attract pollinators by food, sexual, and brood-site mimicry, but other forms of sensory deception may also operate. Helmet orchids （Corybas, Nematoceras and related genera） are often assumed to be brood-site deceivers that mimic the colours and scents of mushrooms to fool female fungus gnats （mycetophilidae） into attempting oviposition and polli- nating flowers. We sampled spectral reflectances and volatile odours of an endemic terrestrial New Zealand orchid Corybas cheesemanii, and co-occurring wild mushrooms. The orchid is scentless to humans and SPmE GC-mS analyses did not detect any odours, but more sensitive methods may be required. The orchids reflected strongly across all visible wavelengths （300-700nm） with peaks in the UV （-320nm）, yellow-green （500-600 nm） and red regions （650-700 nm）, whereas mushrooms and surrounding leaf litter reflected predominantly red and no UV. Rather than mimicking mushrooms, these orchids may attract pollinators by exploiting insects＇ strong sensory bias for UV. modelling spectral reflectances into a categorical fly vision model and a generic tetrachromat vision model provided very different results, but neither suggest any mimicry of mushrooms. However, these models require further assessment and data on fly spectral sensitivity to red wavelengths is lacking - a problem given the predominance of red, fly-pollinated flowers worldwide

关键词： Diptera Colour space Fly pollination Orchidaceae Spectral reflectance Visual modelling

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A 3-D numerical study of solitary wave interaction with vertical cylinders using a parallelised particle-in-cell solver

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Journal of Hydrodynamics 2017年第5期29卷 790-799页

作者： Qiang Chen Jun Zang David m.kelly Aggelos S.Dimakopoulos WEIR Research Unit Department of Architecture and Civil EngineeringUniversity of BathBathUK Coastal Research Laboratory International Hurricane Research CenterFlorida International UniversityMiamiUSA HR Wallingford WallingfordOxonUK

This paper aims to provide a better understanding of the interaction between solitary waves and vertical circular cylinders. This is achieved via process based numerical modelling using the parallel particle-in-cell based incompressible flow solver PICIN. The numerical model solves the Navier-Stokes equations for free-surface flows and incorporates a Cartesian cut cell method for fluid-structure interaction. Solitary waves are generated using a piston-type wave paddle. The PICIN model is first validated using a test case that involves solitary wave scattering by a single vertical cylinder. Comparisons between the present results and experimental data show good agreement for the free surface elevations around the cylinder and the horizontal wave force on the cylinder. The model is then employed to investigate solitary wave interaction with a group of eleven vertical cylinders. The wave run-up and wave forces on the cylinders are discussed.

关键词： CFD hybrid Eulerian-Lagrangian particle-in-cell solitary wave vertical cylinder

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Effects of sun compass error on spatial search by Clark’s nutcrackers

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Integrative Zoology 2019年第2期14卷 172-181页

作者： Debbie m.kelly Ken CHENG Russell BALDA Alan C.KAmIL Department of Psychology University of ManitobaWinnipegCanada Department of Biological Sciences Macquarie UniversitySydneyAustralia Department of Biological Sciences Northern Arizona UniversityFlagstaffUSA Department of Biological Sciences University of Nebraska-LincolnLincolnUSA

Animals employ compasses during navigation,but little attention has been paid to how accuracy is maintained in the face of compass error,which is inevitable in biological *** use of multiple landmarks may minimize the effect of compass *** allowed Clark’s nutcrackers to cache seeds in an outdoor aviary with either one or four landmarks present,and subsequently subjected them to small clock-shifts mimicking the effects of compass *** predicted,the results showed a significant decrease in search accuracy following the clock-shift when one landmark was present but not when four landmarks were *** results support that nutcrackers encode information from the sun as well as terrestrial landmarks,and these spatial cues are used in a flexible ***,our results are important as they support the hypothesis that multiple landmarks may be used during situations where the sun compass has even a small amount of error.

关键词： Clark’s nutcracker clock-shift error landmarks sun compass

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Associations of blood biomarkers with glomerular filtration rate in patients with TIA and stroke: population-based study

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Stroke & Vascular Neurology 2021年第1期6卷 48-56页

作者： Dearbhla m.kelly Linxin Li Annette I Burgess Deborah L Poole Julia m Duerden Peter m.Rothwell Wolfson Centre for the Prevention of Stroke and Dementia Nuffield Department of Clinical NeurosciencesOxford UniversityOxfordUK

Background and purpose Non-traditional risk factors such as chronic inflammation,oxidative stress and thrombogenic factors are believed to contribute to the excess stroke risk in chronic kidney disease(CKD)by triggering vascular injury and endothelial *** aimed to determine how well a panel of biomarkers representative of these factors would correlate with estimated glomerular filtration rate(eGFR)in patients with recent transient ischaemic attack(TIA)or *** also investigated whether eGFR would confound previously reported associations between biomarkers and *** We studied a panel of 16 blood biomarkers related to inflammation,thrombosis,atherogenesis and cardiac or neuronal cell damage in TIA or ischaemic stroke in a population-based study(Oxford Vascular Study).Biomarker levels were log-transformed and correlated with eGFR,adjusted for *** proportional hazard models were used for survival *** Among 1297 patients with TIA or stroke,52.7%(n=684)of patients had CKD(eGFRmL/min/1.73 m^(2)).There was a moderate correlation between log-eGFR and the log-transformed soluble tumour necrosis factor receptor-1(R^(2)=0.21),attenuating with adjustment for age(R^(2)=0.12).There were moderate-to strong correlations with markers of cardiac injury,N-terminal pro-brain natriuretic peptide and heart-type fatty acid binding protein(hFABP,R2=0.14 and 0.34,respectively).The strongest correlation after adjustment for age was between hFABP and eGFR(R^(2)=0.20).Adjusting for eGFR did not impact any biomarker associations with *** Correlations between biomarkers related to inflammation and thrombosis with renal dysfunction in the setting of cerebrovascular events were generally modest after adjustment for age,suggesting that putative risk factors such as chronic inflammation or coagulopathy are unlikely to be important stroke mechanisms in patients with CKD.

关键词： inflammation patients mortality

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Effect of variable heat treatment modes on microstructures of Fe-Cr-Bcast iron alloy

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China Foundry 2008年第1期5卷 28-31页

作者： Guo Changqing Wang Caidong Liu Xiaoping P. m. kelly Inner mongolia University of Science ＆Technology Baotou 014010 Inner Mongolia China Inner mongolia Vocational Colloge of Commerce Hohhot 010010 Inner Mongolia China Division of materials the University of Queensland QLD 4072 Brisbane Australia

The effect of heat treatment mode on the microstructure of Fe-Cr-B cast iron alloys was investigated inthis paper by comparing the difference of precipitation patterns of secondary particles after thermal cycling treatment(TCT) with those after normal heat treatment (NHT). No obvious differences were found in precipitation patterns ofsecondary particles between TCT and NHT when experimental temperature was below Ar1. However, whentemperature was over Ar1, there were significant differences, with secondary particles prominently segregated at thegrain boundaries under TCT, while the particles evenly distributed in the matrix under NHT. The reason for themicrostructure differences could be associated with the development of non-equilibrium segregation of boron duringTCT.

关键词： heat treatment mode microstructures Fe-Cr-B cast irons non-equilibrium segregation of boron

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用菊池衍射测定m_7C_3碳化物与奥氏体间的位向关系

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金属热处理学报 2000年第2期21卷 50-56页

作者：张明星 P.m.kelly Department of mining

用菊池衍射测定相间位向关系新技术对一种白口铸铁中m7C3型碳化物的晶体学进行了研究。结果表明 ,在这一材料中至少m7C3型碳化物属于正交晶系 ,而非一般认为的六方晶系。发现了三种m7C3型碳化物与奥氏体间的位向关系。它们是 :(151) C∥... 详细信息

用菊池衍射测定相间位向关系新技术对一种白口铸铁中m7C3型碳化物的晶体学进行了研究。结果表明 ,在这一材料中至少m7C3型碳化物属于正交晶系 ,而非一般认为的六方晶系。发现了三种m7C3型碳化物与奥氏体间的位向关系。它们是 :(151) C∥ (111) A,[10 1]C∥ [10 1]A 和(311) C∥ (111) A,[0 11]C∥ [0 11　 ]A 以及 (2 4 1) C∥ (111) A,[112 ]C∥ [10 1]A。应用最近提出的“Edge to edge”matching理论可对这一结果作出合理的解释。

关键词：菊池衍射 m7C3型碳化物位向关系奥氏体白口铁

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Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches

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World Journal of Clinical Oncology 2016年第1期7卷 15-26页

作者： Paul L Swiecicki kelly m malloy Francis P Worden Division of Hematology/Oncology Department of Internal Medicine University of Michigan Comprehensive Cancer Center Department of Otolaryngology University of Michigan Health System University of michigan Comprehensive Cancer Center

Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus(HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease.

关键词： Oropharyngeal cancer Human papilloma virus Transoral robotic surgery Immunotherapy metastatic head and neck squamous cell carcinoma

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Collagen-GAG Scaffolds Grafted Onto myocardial Infarcts in a Rat model:A Delivery Vehicle for mesenchymal Stem Cells

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生物医学工程学杂志 2005年第S1期22卷 175-176页

作者： Z.XIANG R.LIAO m.kelly m.SPECTOR Department of Orthopaedic Surgery West China HospitalSichuan UniversityChengdu 610041China Tissue Engineering VA Boston Healthcare SystemBoston CampusBostonMAUSA Whitaker Cardiovascular Institute Boston University School of MedicineBostonMAUSA Harvard medical School BostonMAUSA

1 IntroductionThe objective of the present study was to investigate the response of rat myocardial scar tissue to type Ⅰ collagen-glycosaminoglycan (GAG) tissue engineering scaffolds, and to assess the feasibility of using a collagenGAG scaffold as a delivery vehicle for bone marrow-derived mesenchymal stem cells. The benefits of employing the collagen-GAG scaffold for this application include the following: (1) the large surface area of the three-dimensional sponge-like material allows for the delivery of a high cell density to the infarct site; (2) the scaffold allows for the localization and retention of the cells at the site of implantation; (3) the tissue response to the scaffold may promote angiogenesis at the implant site.

关键词： Collagen scaffold collagen sponge infarct implantation BrdU retention appearance chondroitin

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