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Why endophenotype development requires families

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chinese Science Bulletin 2011年第32期56卷 3382-3384页

作者： GLAHN david c BLANGERO John Department of Psychiatry Yale University School of Medicine New Haven CT 06511 USA Olin Neuropsychiatry Research center Institute of Living Hartford Hospital CT 06106 USA Department of Genetics Texas Biomedical Research Institute San Antonio TX 78227 USA

Endophenotypes are heritable quantitative traits that are associated with disease liability, can be measured in both affected and unaffected individuals, and provide much greater power to localize and identify risk genes for mental illness than does affection status alone. Traditionally, endophenotypic markers for psychiatric illnesses include in vivo neuroanatomic and functional magnetic resonance imaging measurements and indices of neurocognitive abilities. However, neurocognitive and neuroimaging measures are by no means the only classes of endophenotypes that could be useful for identifying genes for mental illness. Given the advantages of endophenotype-based strategies for elucidating the genetic underpinnings of psychiatric disorders, it would seem prudent to develop a wide range of putative endophenotypes. In order for a measure to be considered a valid endophenotype, it must meet a number of criteria. Specifically, the trait must (1) have moderate to high heritability, (2) be associated with the illness, (3) be independent of clinical state, and (4) impairment must co-segregate with the illness within a family, with non-affected family members showing impairment relative to the general population. While each of these criteria is critical, the heritability and co-segregation requirements are really what differentiate an endophenotype from a simple biomarker. At this time, one requires an experimental design that includes families to demonstrate both heritability and co-segregation. The assertion that novel endophenotypes can not be fully established without family data does not preclude work in unrelated individuals, rather that unrelated samples will only be able to nominate potential candidate endophenotypes that subsequently need to be confirmed in family-based experiments.

关键词：家庭成员稳定精神疾病遗传基础数量性状成像测量生物标志物神经管

East meets West:ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and caucasians

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chinese Journal of cancer 2011年第5期30卷 287-292页

作者： Wei Zhou david c. christiani Molecular Epidemiology Research Global Outcomes Research Pfizer Oncology Collegeville PA 19426 USA Departments of Epidemiology and Environmental Health Harvard School of Public Health Boston MA 02115 USA Department of Medicine Massachusetts General Hospital Harvard Medical School Boston MA 02115 USA

Lung cancer is the leading cause of cancer death worldwide,with large variation of the incidence and mortality across *** the mortality of lung cancer has been decreasing,or steady in the US,it has been increasing in Asia for the past two *** is the leading cause of lung cancer,and other risk factors such as indoor coal burning,cooking fumes,and infections may play important roles in the development of lung cancer among Asian never smoking *** median age of diagnosis in Asian patients with lung cancer is generally younger than caucasian patients,particularly among *** and caucasians may have different genetic susceptibilities to lung cancer,as evidenced from candidate polymorphisms and genome-wide association *** epidemiologic studies and clinical trials have shown consistently that Asian ethnicity is a favorable prognostic factor for overall survival in non-small cell lung cancer(NScLc),independent of smoking *** with caucasian patients with NScLc,East Asian patients have a much higher prevalence of epidermal growth factor receptor(EGFR) mutation(approximately 30% vs.7%,predominantly among patients with adenocarcinoma and never-smokers),a lower prevalence of K-Ras mutation(less than 10% vs.18%,predominantly among patients with adenocarcinoma and smokers),and higher proportion of patients who are responsive to EGFR tyrosine kinase *** ethnic differences in epidemiology and clinical behaviors should be taken into account when conducting global clinical trials that include different ethnic populations.

关键词：非小细胞肺癌临床试验种族差异流行病学亚洲人中西文化行为白种人

Successful aspiration and ethanol sclerosis of a large,symptomatic, simple liver cyst:case presentation and review of the literature

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World Journal of Gastroenterology 2006年第18期12卷 2949-2954页

作者： Wojciech c Blonski Mical S campbell Thomas Faust david c Metz Division of Gastroenterology University of PennsylvaniaPhiladelphiaPAUnited States and Department of Gastroenterology and HepatologyWroclaw Medical UniversityPoland Division of Gastroenterology University of PennsylvaniaPhiladelphiaPAUnited States

Simple liver cysts are congenital with a prevalence of 2.5%-4.25%. Imaging, whether by US, cT or MRI, is accurate in distinguishing simple cysts from other etiologies, including parasitic, neoplastic, duct-related, and traumatic cysts. Symptomatic simple liver cysts are rare, and the true frequency of symptoms is not known. Symptomatic simple liver cysts are predominantly large （〉 4 cm）, right-sided, and more common in women and older patients. The vast majority of simple hepatic cysts require no treatment or follow-up, though large cysts （〉 4 cm） may be followed initially with serial imaging to ensure stability. Attribution of symptoms to a large simple cyst should be undertaken with caution, after alternative diagnoses have been excluded. Aspiration may be performed to test whether symptoms are due to the cyst; however, cyst recurrence should be expected. Limited experience with both laparoscopic deroofing and aspiration, followed by instillation of a sclerosing agent has demonstrated promising results for the treatment of symptomatic cysts. Here, we describe a patient with a large, symptomatic, simple liver cyst who experienced complete resolution of symptoms following cyst drainage and alcohol ablation, and we present a comprehensive review of the literature.

关键词： Simple hepatic cyst Alcohol sclerosis Laparoscopic deroofing

Elevated plasma levels of N-terminal pro-brain natriuretic peptide in patients with chronic hepatitis c during interferon-based antiviral therapy

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World Journal of Gastroenterology 2006年第36期12卷 5875-5877页

作者： Jrg Bojunga christoph Sarrazin Georg hess Stefan Zeuzem Internal Medicine Ⅱ Saarland University Hospital 66421 Homburg/Saar Germany Roche Diagnostics 68305 Mannheim Germany

AIM: To investigate plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), an established marker of cardiac function, in patients with chronic hepatitis c during interferon-based antiviral therapy. METHODS: Using a sandwich immunoassay, plasma levels of NT-proBNP were determined in 48 patients with chronic hepatitis c at baseline, wk 24 and 48 during antiviral therapy and at wk 72 during ***: Plasma NT-proBNP concentrations were significantly increased (P compared to the baseline values. NT-proBNP concentrations at baseline and wk 24 were closely correlated (r = 0.8; P concentrations above 200 ng/L compared to 1 (2%) patient at baseline (P = 0.059). Six of these 7 patients had been treated with high-dose IFN-α induction therapy. In multiple regression analysis, NT-proBNP was not related to other clinical parameters, biochemical parameters of liver disease or virus load and response to ***: Elevated levels of NT-proBNP during and after interferon-based antiviral therapy of chronic hepatitis c may indicate the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in patients during therapy. Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding therapy in patients during interferon-based antiviral therapy.

关键词： Hepatitis c N-terminal pro-brain natriuretic peptide Interferon cardiomyopathy Treatment side effects

Physical activity lowers the risk for acute respiratory infections:Time for recognition

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Journal of Sport and Health Science 2022年第6期11卷 648-655,F0003页

作者： david c.Nieman camila A.Sakaguchi Human Performance Laboratory Appalachian State UniversityNorth Carolina Research CampusKannapolisNC 28081USA

Physical inactivity is a well-established risk factor for chronic diseases,such as cardiovascular disease,cancer,and diabetes *** is a growing awareness that physical inactivity should also be regarded as a risk factor for acute respiratory infections(ARIs).ARIs,such as the common cold,influenza,pneumonia,and coronavirus disease 2019(cOVID-19),are among the most pervasive diseases on earth and cause widespread morbidity and *** in support of the linkage between ARIs and physical inactivity has been strengthened during the cOVID-19 pandemic because of increased scientific ***-scale studies have consistently reported that the risk for severe cOVID-19 outcomes is elevated in cohorts with low physical activity and/or physical fitness,even after adjusting for other risk *** lowered risk for severe cOVID-19 and other ARIs in physically active groups is attributed to exercise-induced immunoprotective effects,including enhanced surveillance of key immune cells and reduced chronic *** consensus groups,including those who submitted the Physical Activity Guidelines for Americans,have not yet given this area of research the respect that is *** is time to add“reduced risk for ARIs”to the“Exercise is Medicine”list of physical activity-related health benefits.

关键词： Acute respiratory infections cOVID-19 Immune system Physical activity Pneumonia

Flow resistance of gravel bed channels

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International Journal of Sediment Research 2014年第1期29卷 126-132页

作者： Wen c.WANG david R.DAWDY Multech Engineering consultants

Existing resistance formulas produce a wide range of friction-factor estimates for gravel bed *** purpose of this paper is to develop a reliable resistance formula in terms of the Darcy-Weisbach friction factor/ Published data were screened and used to establish the *** existing formulas have considered that/is a function of relative roughness D84/R only,where R is the hydraulic radius and D84is the particle size referred to the intermediate diameter that equals or exceeds that of 84 percent of bed *** this paper,/is considered as a function of Froude number in addition to the relative roughness./for D84/R>1 displays a different trend than that for D84/Rc velocity distribution for D84/R>***/formula for D84/R<1 has been established.

关键词： Flow resistance Darcy-Weisbach friction factor Relative roughness Relative submergence Gravel bed channels Open channels

cost-Effectiveness of Interventions for Alternate Food to Address Agricultural catastrophes Globally

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International Journal of Disaster Risk Science 2016年第3期7卷 205-215页

作者： david c.Denkenberger Joshua M.Pearce Global catastrophic Risk Institute Department of civil and Architectural Engineering Tennessee State University Department of Materials Science and Engineering Michigan Technological University Department of Electrical and computer Engineering Michigan Technological University

The literature suggests there is about a 1 % risk per year of a 10 % global agricultural shortfall due to catastrophes such as a large volcanic eruption, a medium asteroid or comet impact, regional nuclear war, abrupt climate change, and extreme weather causing multiple breadbasket failures. This shortfall has an expected mortality of about 500 million people. To prevent such mass starvation, alternate foods can be deployed that utilize stored biomass. This study developed a model with literature values for variables and, where no values existed,used large error bounds to recognize uncertainty. Then Monte carlo analysis was performed on three interventions: planning, research, and development. The results show that even the upper bound of USD 400 per life saved by these interventions is far lower than what is typically paid to save a life in a less-developed country. Furthermore, every day of delay on the implementation of these interventions costs 100–40,000 expected lives(number of lives saved multiplied by the probability that alternate foods would be required). These interventions plus training would save 1–300 million expected lives. In general, these solutions would reduce the possibility of civilization collapse, could assist in providing food outside of catastrophic situations, and would result in billions of dollars per year of return.

关键词： Agricultural catastrophe Alternate food Global catastrophic risk Intervention cost-effectiveness

Fit to fight——from military hygiene to wellbeing in the British Army

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Military Medical Research 2020年第4期7卷 482-488页

作者： Martin c.M.Bricknell colonel david A.Ross Health and Military Medicine Conflict and Health Research GroupSchool of Security StudiesKing’s College LondonStrand CampusLondon WC2R 2LSUK Parkes Professor of Preventive Medicine Robertson HouseCamberley GU154NAUK

This paper reviews the historical evolution of the language and organization surrounding the health of personnel in the British Army from‘hygiene’through to‘wellbeing’.It starts by considering the health of the army in the midnineteenth century and the emergence of military hygiene as a professional *** continues by looking at advances in military hygiene in the two world *** was replaced by the term‘health’in the 1950 s as the collective noun used by professionals working in this *** unity split when the professions of occupational medicine and public health established separate faculties and training ***,the health issues for the armed forces remain fundamentally *** forward,the term‘wellbeing’is helping to refresh the close relationships between executives,their medical advisers and those within the population of health professions charged with keeping the British Army *** core theme is the collaborations between civil society,executive leadership and medical services in maximizing the health of the military population from recruitment through to life as a veteran.

关键词： Public health Hygiene Occupational medicine

Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

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World Journal of Gastrointestinal Oncology 2014年第6期6卷 145-155页

作者： Elizabeth c Smyth david cunningham Department of Gastrointestinal Oncology Royal Marsden Hospital

Oesophageal junctional adenocarcinoma is a challeng-ing and increasingly common disease. Optimisation ofpre-operative staging and consolidation of surgery inlarge volume centres have improved outcomes, howev-er the preferred adjunctive treatment approach remainsa matter of debate. This review examines the benefitsof neoadjuvant, peri-operative, and post-operative che-motherapy and chemoradiotherapy in this setting in anattempt to reach an evidence based conclusion. Recentfindings relating to the molecular characterisation ofoesophagogastric cancer and their impact on therapeu-tics are explored, in addition to the potential benefitsof fluoro-deoxyglucose positron emission tomography(FDG-PET) directed therapy. Finally, efforts to decreasethe incidence of junctional adenocarcinoma using earlyintervention in Barrett's oesophagus are discussed,including the roles of screening, endoscopic mucosalresection, ablative therapies and chemoprevention.

关键词： Oesophageal adenocarcinoma Junctional adenocarcinoma Gastric adenocarcinoma Peri-operative chemotherapy Pre-operative chemoradiotherapy Molecular profiling Fluoro-deoxyglucose-positron emission tomography Barrett's oesophagus chemoprevention