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Find video protocols related to scientific articles indexed in Pubmed.
Using the TIME model in Spectrum to estimate tuberculosis-HIV incidence and mortality.
AIDS
PUBLISHED: 11-20-2014
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Reliable estimates of the joint burden of HIV and tuberculosis epidemics are crucial to planning strategic global and national tuberculosis responses. Prior to the Global Tuberculosis Report 2013, the Global Tuberculosis Programme (GTB) released estimates for tuberculosis-HIV incidence at the global level only. Neither GTB nor United Nations Programme on HIV/AIDS (UNAIDS) published country specific estimates for tuberculosis-HIV mortality. We used a regression approach that combined all available data from GTB and UNAIDS in order to estimate tuberculosis-HIV incidence and mortality at country level.
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Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-06-2014
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To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middle-income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.
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A retrospective descriptive analysis of patient adherence to dabigatran at a large academic medical center.
J Manag Care Pharm
PUBLISHED: 10-04-2014
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Clinical trials evaluating the efficacy of dabigatran followed a very strict protocol, which included close monitoring and follow-up. Patients followed in this controlled environment had an average medication possession ratio (MPR) greater than?0.95. However, very few studies have evaluated patient adherence to dabigatran in a real-world setting. Other studies of chronic medications indicate patients are not reliably adherent to twice daily regimens. Adherence to therapy is particularly important for direct thrombin inhibitors because there may be a risk of increased thromboembolic events associated with poor adherence to these agents. 
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The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets.
Lancet Diabetes Endocrinol
PUBLISHED: 09-08-2014
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To achieve the post-2015 global tuberculosis target of 90% reduction in tuberculosis incidence by 2035, the present rate of decline must accelerate. Among factors that hinder tuberculosis control, malnutrition and diabetes are key challenges. We review available data to describe the complex relationship between tuberculosis, diabetes, and nutritional status. Additionally, we review past trends, present burden, and available future global projections for diabetes, overweight and obesity, as well as undernutrition and food insecurity. Using a mathematical model, we estimate the potential effect of these factors on tuberculosis burden up to 2035. Great potential exists for reduction of worldwide tuberculosis burden by combination of improved prevention and care of diabetes with reduction of undernutrition. To achieve this combination will require joint efforts and strong cross-programme links, enabling synergistic effects of public health policies that promote good nutrition and optimum clinical care for tuberculosis and diabetes.
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Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome.
Cancer Immunol. Immunother.
PUBLISHED: 08-19-2014
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Interleukin-2 (IL-2) therapy leads to clinically relevant responses in 10-16 % of patients with metastatic melanoma (MMEL) or 10-30 % of patients with metastatic renal cell carcinoma (MRCC). To date, no biomarkers have been validated to identify patients who are likely to respond. We hypothesized that changes in T cell subset distribution in patients undergoing IL-2 therapy may correlate with treatment outcomes. Immune profiles of 64 patients (27-MMEL, 37-MRCC) were evaluated using flow cytometry at baseline, during (?three doses) and at the end of treatment cycle (30 ± 6 h after last dose), through two courses of IL-2 therapy. Changes in distribution and phenotype of circulating CD4 and CD8 lymphocyte subsets were compared (1) based on cancer types and (2) intra-patient during the course of the IL-2 therapy. Exploratory analysis of immunologic profiles was also performed based on treatment outcome. Independent of cancer type, IL-2 led to a transient decrease of circulating effector lymphocytes, while regulatory T cells gradually increased. Interleukin-2 differentially affected a subset of CD8 T cell expressing Foxp3, depending on malignancy type. In MMEL patients, IL-2 gradually expanded circulating CD8 Foxp3+ cells; in MRCC patients, IL-2 transiently increased expression of CD103 and CCR4 homing markers. Monitoring of adaptive immune variables early on and during the course of IL-2 therapy revealed transient alterations in immune profiles, specific to MMEL and MRCC patients, related to immune balance (and ultimately response to IL-2 therapy) or T cell egress from the circulation.
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Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.
Lancet Glob Health
PUBLISHED: 08-09-2014
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New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per ?L or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage.
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Preclinical feasibility of a technology framework for MRI-guided iliac angioplasty.
Int J Comput Assist Radiol Surg
PUBLISHED: 08-08-2014
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Interventional MRI has significant potential for image guidance of iliac angioplasty and related vascular procedures. A technology framework with in-room image display, control, communication and MRI-guided intervention techniques was designed and tested for its potential to provide safe, fast and efficient MRI-guided angioplasty of the iliac arteries.
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Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Christopher J L Murray, Katrina F Ortblad, Caterina Guinovart, Stephen S Lim, Timothy M Wolock, D Allen Roberts, Emily A Dansereau, Nicholas Graetz, Ryan M Barber, Jonathan C Brown, Haidong Wang, Herbert C Duber, Mohsen Naghavi, Daniel Dicker, Lalit Dandona, Joshua A Salomon, Kyle R Heuton, Kyle Foreman, David E Phillips, Thomas D Fleming, Abraham D Flaxman, Bryan K Phillips, Elizabeth K Johnson, Megan S Coggeshall, Foad Abd-Allah, Semaw Ferede Abera, Jerry P Abraham, Ibrahim Abubakar, Laith J Abu-Raddad, Niveen Me Abu-Rmeileh, Tom Achoki, Austine Olufemi Adeyemo, Arsène Kouablan Adou, José C Adsuar, Emilie Elisabet Agardh, Dickens Akena, Mazin J Al Kahbouri, Deena Alasfoor, Mohammed I Albittar, Gabriel Alcalá-Cerra, Miguel Angel Alegretti, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, François Alla, Peter J Allen, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Benjamin O Anderson, Carl Abelardo T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Amitava Banerjee, Sanjay Basu, Justin Beardsley, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku Jibat Beyene, Neeraj Bhala, Ashish Bhalla, Zulfiqar A Bhutta, Aref Bin Abdulhak, Agnes Binagwaho, Jed D Blore, Berrak Bora Basara, Dipan Bose, Michael Brainin, Nicholas Breitborde, Carlos A Castañeda-Orjuela, Ferrán Catalá-López, Vineet K Chadha, Jung-Chen Chang, Peggy Pei-Chia Chiang, Ting-Wu Chuang, Mercedes Colomar, Leslie Trumbull Cooper, Cyrus Cooper, Karen J Courville, Benjamin C Cowie, Michael H Criqui, Rakhi Dandona, Anand Dayama, Diego De Leo, Louisa Degenhardt, Borja del Pozo-Cruz, Kebede Deribe, Don C Des Jarlais, Muluken Dessalegn, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Tim R Driscoll, Adnan M Durrani, Richard G Ellenbogen, Sergey Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Seyed-Mohammad Fereshtehnejad, Daniel Obadare Fijabi, Mohammad H Forouzanfar, Urbano Fra Paleo, Lynne Gaffikin, Amiran Gamkrelidze, Fortuné Gbètoho Gankpé, Johanna M Geleijnse, Bradford D Gessner, Katherine B Gibney, Ibrahim Abdelmageem Mohamed Ginawi, Elizabeth L Glaser, Philimon Gona, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rajeev Gupta, Rahul Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Josep Maria Haro, Rasmus Havmoeller, Simon I Hay, Mohammad T Hedayati, Ileana B Heredia Pi, Hans W Hoek, John C Hornberger, H Dean Hosgood, Peter J Hotez, Damian G Hoy, John J Huang, Kim M Iburg, Bulat T Idrisov, Kaire Innos, Kathryn H Jacobsen, Panniyammakal Jeemon, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Haidong Kan, Ida Kankindi, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Andre Keren, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Irma Khonelidze, Yohannes Kinfu, Jonas M Kinge, Luke Knibbs, Yoshihiro Kokubo, S Kosen, Barthélemy Kuate Defo, Veena S Kulkarni, Chanda Kulkarni, Kaushalendra Kumar, Ravi B Kumar, G Anil Kumar, Gene F Kwan, Taavi Lai, Arjun Lakshmana Balaji, Hilton Lam, Qing Lan, Van C Lansingh, Heidi J Larson, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Yichong Li, Yongmei Li, Graça Maria Ferreira De Lima, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Paulo A Lotufo, Vasco Manuel Pedro Machado, Jennifer H MacLachlan, Carlos Magis-Rodríguez, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Joseph R Masci, Mohammad Taufiq Mashal, Amanda J Mason-Jones, Bongani M Mayosi, Tasara T Mazorodze, Abigail Cecilia Mckay, Peter A Meaney, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Yohannes Adama Melaku, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Karzan Abdulmuhsin Mohammad, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Marcella Montico, Ami R Moore, Rintaro Mori, Wilkister Nyaora Moturi, Mitsuru Mukaigawara, Kinnari S Murthy, Aliya Naheed, Kovin S Naidoo, Luigi Naldi, Vinay Nangia, K M Venkat Narayan, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Vincent Nowaseb, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Aslam Pervaiz, Konrad Pesudovs, Max Petzold, Farshad Pourmalek, Dima Qato, Amado D Quezada, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Homie Razavi, Robert Quentin Reilly, Giuseppe Remuzzi, Jan Hendrik Richardus, Luca Ronfani, Nobhojit Roy, Nsanzimana Sabin, Mohammad Yahya Saeedi, Mohammad Ali Sahraian, Genesis May J Samonte, Monika Sawhney, Ione J C Schneider, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Rupak Shivakoti, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Edgar P Simard, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Samir Soneji, Sergey S Soshnikov, Chandrashekhar T Sreeramareddy, Vasiliki Kalliopi Stathopoulou, Konstantinos Stroumpoulis, Soumya Swaminathan, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Alan J Thomson, Andrew L Thorne-Lyman, Jeffrey A Towbin, Jefferson Traebert, Bach X Tran, Zacharie Tsala Dimbuene, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Selen Begüm Uzun, Andrew J Vallely, Tommi J Vasankari, N Venketasubramanian, Francesco S Violante, Vasiliy Victorovich Vlassov, Stein Emil Vollset, Stephen Waller, Mitchell T Wallin, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, Richard A White, James D Wilkinson, Thomas Neil Williams, Solomon Meseret Woldeyohannes, John Q Wong, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Theo Vos.
Lancet
PUBLISHED: 07-22-2014
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The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
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A novel tumor necrosis factor-mediated mechanism of direct epithelial sodium channel activation.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 07-17-2014
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Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar epithelial cells. Dysfunction of these Na(+) transporters during pulmonary inflammation can contribute to pulmonary edema.
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Remedial action in the management of wound-related pain.
Nurs Stand
PUBLISHED: 07-17-2014
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Wound-related pain, particularly following wound care interventions, is a concern to all involved in wound management. However, little is understood about how remedial action to manage such pain can affect healthcare provision, particularly in terms of resources. This article describes a Delphi study - a process of gaining expert consensus in a particular area - identifying the main factors influenced by the presence of pain at wound dressing change. It was found that the presence of pain influences the choice and frequency of analgesia, use of anxiolytic medications, frequency of dressing change and the environment in which care is provided. These results can help clinicians to understand the close relationship that exists between pain and clinical intervention, and the implications for resource management.
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Graphene nanoarchitecture in batteries.
Nanoscale
PUBLISHED: 07-04-2014
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We compare three different carbon nanoarchitectures used to produce standard coin cell batteries: graphene monolayer, graphite paper and graphene foam. The batteries' electrochemical performances are characterised using cyclic voltammetry, constant-current discharge and dynamic galvanostatic techniques. Even though graphene is the fundamental building block of graphite its properties are intrinsically different when used in batteries because there is no ion intercalation in graphene. The nanoarchitecture of the graphene electrode is shown to have a strong influence over the battery's electrochemical performance. This provides a versatile way to design various battery electrodes on different demands.
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ACR appropriateness criteria® nonischemic myocardial disease with clinical manifestations (ischemic cardiomyopathy already excluded).
J Thorac Imaging
PUBLISHED: 06-07-2014
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Nonischemic myocardial disease or cardiomyopathy can present as arrhythmia, palpitations, heart failure, dyspnea, lower extremity edema, ascites, syncope, and/or chest discomfort and can be classified as either systolic, diastolic, or a combination of both. Echocardiography is the mainstay of evaluating left ventricular function. However, cardiac magnetic resonance imaging (MRI) is now considered the reference standard imaging technique to assess myocardial anatomy, function, and viability. Advanced MRI techniques with delayed myocardial enhancement, especially, can provide information beyond echocardiography for tissue characterization in CM and can assist in determining specific etiology or in narrowing the differential. Often imaging enhancement patterns, signal characteristics, and morphology on MRI can lead to specific diagnoses such as amyloidosis, hypertrophic CM, or iron deposition. Cardiac computed tomography is usually used in excluding coronary artery disease but can also be used in some patients unable to undergo cardiac MRI to assess arrhythmogenic right ventricular dysplasia. Both 18-F-fluoro-2-deoxyglucose positron emission tomography and delayed contrast-enhanced MRI can be used to assess for cardiac sarcoidosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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A marine inducible prophage vB_CibM-P1 isolated from the aerobic anoxygenic phototrophic bacterium Citromicrobium bathyomarinum JL354.
Sci Rep
PUBLISHED: 05-13-2014
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A prophage vB_CibM-P1 was induced by mitomycin C from the epipelagic strain Citromicrobium bathyomarinum JL354, a member of the alpha-IV subcluster of marine aerobic anoxygenic phototrophic bacteria (AAPB). The induced bacteriophage vB_CibM-P1 had Myoviridae-like morphology and polyhedral heads (approximately capsid 60-100?nm) with tail fibers. The vB_CibM-P1 genome is ~38?kb in size, with 66.0% GC content. The genome contains 58 proposed open reading frames that are involved in integration, DNA packaging, morphogenesis and bacterial lysis. VB_CibM-P1 is a temperate phage that can be directly induced in hosts. In response to mitomycin C induction, virus-like particles can increase to 7 × 10(9) per ml, while host cells decrease an order of magnitude. The vB_CibM-P1 bacteriophage is the first inducible prophage from AAPB.
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Factors affecting cost-effectiveness in wound care decision making.
Nurs Stand
PUBLISHED: 05-01-2014
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With increasing health service cutbacks, cost-effectiveness is a central issue in many wound care decisions. Clinicians are frequently required to justify clinical decision making in terms of health benefits obtained and the cost to health service providers. However, few clinicians have the skills to accurately interpret cost in more than local health economic terms, and the disjointed structures that exist in healthcare provision mean that even those who monitor health expenditure have little concept of the global cost of care provision. This article focuses on the pressures placed on healthcare providers to achieve cost-effectiveness in care, specifically in relation to wound care and the effect that pain at dressing change has on the cost of care.
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24/7/365 in-house radiologist coverage: effect on resident education.
Acad Radiol
PUBLISHED: 04-13-2014
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To compare programs with and without 24-hour/7 days a week/365 days a year (24/7/365) in-house radiologist coverage regarding resident perceptions of their on-call experience, volume of resident dictations on call, and report turnaround time.
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Zebrafish models of cancer: progress and future challenges.
Curr. Opin. Genet. Dev.
PUBLISHED: 03-25-2014
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The need for scalable strategies to probe the biological consequences of candidate cancer genes has never been more pressing. The zebrafish, with its capacity for high-throughput transgenesis, in vivo imaging and chemical/genetic screening, has ideal features for undertaking this task. Unique biological insights from zebrafish have already led to the identification of novel oncogenic drivers and small molecules being used to treat the human cancer. This review summarizes the recent main findings and describes pertinent areas where the zebrafish can greatly contribute to our understanding of cancer biology and treatment.
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Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-24-2014
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Trials of isoniazid preventive therapy (IPT) for people living with HIV in southern Africa have shown high rates of tuberculosis disease immediately after cessation of therapy. This could be due to the lack of cure following preventive therapy or reinfection with rapid progression to disease. Using a model fitted to trial data, we estimate the degree to which preventive therapies cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-tuberculosis-burden settings. We identified randomized controlled trials that compared IPT to placebo or alternative regimen in HIV-positive, tuberculin skin test positive individuals. A mathematical model describing tuberculosis transmission in a closed cohort of HIV-positive, M. tuberculosis infected, antiretroviral therapy naive individuals following completion of preventive therapy (or placebo) was fitted to posttherapy tuberculosis rates to estimate the annual risk of M. tuberculosis reinfection and the proportion of individuals whose latent infection was cured after therapy. Three trials met our inclusion criteria. Estimated annual risks of reinfection ranged between 3.7 and 4.9%. Our results suggest 6 mo of isoniazid cured in a small proportion [estimated proportion cured = 0% (interquartile range 0-30.9%)]. The proportion cured for 3-mo regimens containing rifampicin or rifapentine was 19-100%. IPT alone does not cure existing infections in the majority of HIV-infected individuals. In high-incidence settings, continuous IPT should be integrated with HIV care. Where the risk of reinfection is lower, preventive therapy with more curative drugs should be preferred for HIV-positive individuals to achieve durable patient benefit.
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Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe: 1990-2010.
Br J Ophthalmol
PUBLISHED: 03-24-2014
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To assess prevalence and causes of blindness and vision impairment in high-income regions and in Central/Eastern Europe in 1990 and 2010.
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G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease.
World J Cardiol
PUBLISHED: 03-06-2014
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Coronary heart disease (CHD) continues to be the greatest mortality risk factor in the developed world. Estrogens are recognized to have great therapeutic potential to treat CHD and other cardiovascular diseases; however, a significant array of potentially debilitating side effects continues to limit their use. Moreover, recent clinical trials have indicated that long-term postmenopausal estrogen therapy may actually be detrimental to cardiovascular health. An exciting new development is the finding that the more recently discovered G-protein-coupled estrogen receptor (GPER) is expressed in coronary arteries-both in coronary endothelium and in smooth muscle within the vascular wall. Accumulating evidence indicates that GPER activation dilates coronary arteries and can also inhibit the proliferation and migration of coronary smooth muscle cells. Thus, selective GPER activation has the potential to increase coronary blood flow and possibly limit the debilitating consequences of coronary atherosclerotic disease. This review will highlight what is currently known regarding the impact of GPER activation on coronary arteries and the potential signaling mechanisms stimulated by GPER agonists in these vessels. A thorough understanding of GPER function in coronary arteries may promote the development of new therapies that would help alleviate CHD, while limiting the potentially dangerous side effects of estrogen therapy.
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Prevalence and causes of vision loss in North Africa and the Middle East: 1990-2010.
Br J Ophthalmol
PUBLISHED: 03-03-2014
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To describe the prevalence and causes of visual impairment and blindness in North Africa and the Middle East (NAME) in 1990 and 2010.
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Prevalence and causes of vision loss in sub-Saharan Africa: 1990-2010.
Br J Ophthalmol
PUBLISHED: 02-25-2014
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To estimate the magnitude, temporal trends and subregional variation in the prevalence of blindness, and moderate/severe vision impairment (MSVI) in sub-Saharan Africa.
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The dual impact of antiretroviral therapy and sexual behaviour changes on HIV epidemiologic trends in Uganda: a modelling study.
Sex Transm Infect
PUBLISHED: 02-24-2014
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Antiretroviral therapy (ART) availability in a population may influence risky sexual behaviour. We examine the potential impact of ART on the HIV epidemic, incorporating evidence for the impact that ART may have on risky sexual behaviour.
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Visual impairment and blindness due to macular diseases globally: a systematic review and meta-analysis.
Am. J. Ophthalmol.
PUBLISHED: 02-11-2014
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To estimate the number of people visually impaired or blind due to macular diseases except those caused by diabetic maculopathy.
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Prevalence and causes of vision loss in Latin America and the Caribbean: 1990-2010.
Br J Ophthalmol
PUBLISHED: 02-11-2014
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To present regional estimates of the magnitude and temporal trends in the prevalence and causes of blindness and moderate/severe visual impairment (MSVI) in Latin America and the Caribbean (LAC).
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Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder.
Psychiatry Res
PUBLISHED: 02-07-2014
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Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks.
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Psychosocial predictors of attitudes toward physician empathy in clinical encounters among 4732 1st year medical students: a report from the CHANGES study.
Patient Educ Couns
PUBLISHED: 02-05-2014
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Medical school curricula intended to promote empathy varies widely. Even the most effective curricula leave a significant group of students untouched. Pre-existing student factors influence their response to learning experiences. We examined the individual predictors of first semester medical students' attitudes toward the value of physician empathy in clinical encounters.
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Rapid acquisition technique for MR elastography of the liver.
Magn Reson Imaging
PUBLISHED: 02-05-2014
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Magnetic resonance elastography (MRE) of the liver is a novel noninvasive clinical diagnostic tool to stage fibrosis based on measured stiffness. The purpose of this study is to design, evaluate and validate a rapid MRE acquisition technique for noninvasively quantitating liver stiffness which reduces by half the scan time, thereby decreasing image registration errors between four MRE phase offsets. In vivo liver MRE was performed on 16 healthy volunteers and 14 patients with biopsy-proven liver fibrosis using the standard clinical gradient recalled echo (GRE) MRE sequence (MREs) and a developed rapid GRE MRE sequence (MREr) to obtain the mean stiffness in an axial slice. The mean stiffness values obtained from the entire group using MREs and MREr were 2.72±0.85 kPa and 2.7±0.85 kPa, respectively, representing an insignificant difference. A linear correlation of R(2)=0.99 was determined between stiffness values obtained using MREs and MREr. Therefore, we can conclude that MREr can replace MREs, which reduces the scan time to half of that of the current standard acquisition (MREs), which will facilitate MRE imaging in patients with inability to hold their breath for long periods.
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The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models.
AIDS
PUBLISHED: 01-29-2014
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Many countries are considering expanding HIV treatment following recent findings emphasizing the effects of antiretroviral therapy (ART) on reducing HIV transmission in addition to already established survival benefits. Given the close interaction of tuberculosis (TB) and HIV epidemics, ART expansion could have important ramifications for TB burden. Previous studies suggest a wide range of possible TB impacts following ART expansion. We used three independently developed TB-HIV models to estimate the TB-related impact of expanding ART in South Africa.
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Neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation.
Chem. Biol.
PUBLISHED: 01-23-2014
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Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor 1-(2-[trifluoromethyl] phenyl) imidazole (TRIM) abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with overexpression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complementary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation, and convergence during craniofacial morphogenesis.
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Prevalence and causes of vision loss in Central and South Asia: 1990-2010.
Br J Ophthalmol
PUBLISHED: 01-23-2014
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To examine the prevalence, patterns and trends of vision impairment and its causes from 1990 to 2010 in Central and South Asia.
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Looking upstream to prevent HIV transmission: can interventions with sex workers alter the course of HIV epidemics in Africa as they did in Asia?
AIDS
PUBLISHED: 01-10-2014
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High rates of partner change in 'upstream' sex work networks have long been recognized to drive 'downstream' transmission of sexually transmitted infections (STIs). We used a stochastic microsimulation model (STDSIM) to explore such transmission dynamics in a generalized African HIV epidemic.
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Prevalence and causes of vision loss in East Asia: 1990-2010.
Br J Ophthalmol
PUBLISHED: 01-03-2014
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To describe the prevalence and causes of visual impairment and blindness in East Asia in 1990 and 2010.
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The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment.
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Modeling of novel diagnostic strategies for active tuberculosis - a systematic review: current practices and recommendations.
PLoS ONE
PUBLISHED: 01-01-2014
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The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB.
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Dysfunction and Dysconnection in Cortical-Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function.
Front Psychiatry
PUBLISHED: 01-01-2014
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Abnormalities in the brain's attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120?s), visual control (passive viewing; 120?s), and rest (20?s) epochs. Low and high demand attention conditions were created using the rapid presentation of two- or three-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: relative to typical controls (TC), HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using dynamic causal modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random-effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and dysconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk-state for psychiatric illness.
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Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.
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Estimation of the HIV basic reproduction number in rural south west Uganda: 1991-2008.
PLoS ONE
PUBLISHED: 01-01-2014
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The basic reproduction number, [Formula: see text], is one of the many measures of the epidemic potential of an infection in a population. We estimate HIV [Formula: see text] over 18 years in a rural population in Uganda, examine method-specific differences in estimated [Formula: see text], and estimate behavioural changes that would reduce [Formula: see text] below one.
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Community understanding of Respondent-Driven Sampling in a medical research setting in Uganda: importance for the use of RDS for public health research.
Int J Soc Res Methodol
PUBLISHED: 11-26-2013
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Respondent-driven sampling (RDS) is a widely-used variant of snowball sampling. Respondents are selected not from a sampling frame, but from a social network of existing members of the sample. Incentives are provided for participation and for the recruitment of others. Ethical and methodological criticisms have been raised about RDS. Our purpose was to evaluate whether these criticisms were justified. In this study RDS was used to recruit male household heads in rural Uganda. We investigated community members understanding and experience of the method, and explored how these may have affected the quality of the RDS survey data. Our findings suggest that because participants recruit participants, the use of RDS in medical research may result in increased difficulties in gaining informed consent, and data collected using RDS may be particularly susceptible to bias due to differences in the understanding of key concepts between researchers and members of the community.
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Psychiatric presentation of sporadic creutzfeldt-jakob disease: a challenge to current diagnostic criteria.
J Neuropsychiatry Clin Neurosci
PUBLISHED: 11-20-2013
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Pathological diagnosis remains the gold standard for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), but being able to differentiate between CJD and non-prion diseases clinically is important because many of the non-prion, rapidly progressive dementias are treatable. Diagnostic criteria need both high sensitivity and specificity while remaining applicable to clinical practice. Despite extensive updates to the clinical criteria for sCJD, there remains a heavy emphasis on neurological signs. We describe a psychiatric presentation of sCJD that did not fulfill the diagnostic criteria until very late in a prolonged disease course and required biopsy for diagnosis.
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A cdx4-sall4 regulatory module controls the transition from mesoderm formation to embryonic hematopoiesis.
Stem Cell Reports
PUBLISHED: 11-19-2013
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Deletion of caudal/cdx genes alters hox gene expression and causes defects in posterior tissues and hematopoiesis. Yet, the defects in hox gene expression only partially explain these phenotypes. To gain deeper insight into Cdx4 function, we performed chromatin immunoprecipitation sequencing (ChIP-seq) combined with gene-expression profiling in zebrafish, and identified the transcription factor spalt-like 4 (sall4) as a Cdx4 target. ChIP-seq revealed that Sall4 bound to its own gene locus and the cdx4 locus. Expression profiling showed that Cdx4 and Sall4 coregulate genes that initiate hematopoiesis, such as hox, scl, and lmo2. Combined cdx4/sall4 gene knockdown impaired erythropoiesis, and overexpression of the Cdx4 and Sall4 target genes scl and lmo2 together rescued the erythroid program. These findings suggest that auto- and cross-regulation of Cdx4 and Sall4 establish a stable molecular circuit in the mesoderm that facilitates the activation of the blood-specific program as development proceeds.
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Ultrafast graphene oxide humidity sensors.
ACS Nano
PUBLISHED: 11-12-2013
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Sensors allow an electronic device to become a gateway between the digital and physical worlds, and sensor materials with unprecedented performance can create new applications and new avenues for user interaction. Graphene oxide can be exploited in humidity and temperature sensors with a number of convenient features such as flexibility, transparency and suitability for large-scale manufacturing. Here we show that the two-dimensional nature of graphene oxide and its superpermeability to water combine to enable humidity sensors with unprecedented response speed (?30 ms response and recovery times). This opens the door to various applications, such as touchless user interfaces, which we demonstrate with a whistling recognition analysis.
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Health literacy, physician trust, and diabetes-related self-care activities in Hispanics with limited resources.
J Health Care Poor Underserved
PUBLISHED: 11-05-2013
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Hispanics with diabetes often have deficits in health literacy (HL). We examined the association among HL, psychosocial factors, and diabetes-related self-care activities.
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Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma.
J. Clin. Oncol.
PUBLISHED: 11-04-2013
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Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma.
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Early feeding and risk of celiac disease in a prospective birth cohort.
Pediatrics
PUBLISHED: 10-07-2013
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Timing of gluten introduction has been associated with the risk of celiac disease (CD) in children, but the optimal time window is unknown. We aimed to study the effect of age of gluten introduction on the risk of CD, adjusting for continued breastfeeding.
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The association of acculturation and health literacy, numeracy and health-related skills in Spanish-speaking caregivers of young children.
J Immigr Minor Health
PUBLISHED: 09-21-2013
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Little is known about the relationship among acculturation, literacy, and health skills in Latino caregivers of young children. Latino caregivers of children < 30 months seeking primary care at four medical centers were administered measures of acculturation (SASH), functional health literacy (STOFHLA), numeracy (WRAT-3) and health-related skills (PHLAT Spanish). Child anthropomorphics and immunization status were ascertained by chart review. Caregivers (N = 184) with a median age of 27 years (IQR: 23-32) participated; 89.1% were mothers, and 97.1% had low acculturation. Lower SASH scores were significantly correlated (P < 0.01) with lower STOFHLA (? = 0.21), WRAT-3 (? = 0.25), and PHLAT Spanish scores (? = 0.34). SASH scores predicted PHLAT Spanish scores in a multivariable linear regression model that adjusted for the age of child, the age and gender of the caregiver, number of children in the family, the type of health insurance of the caregiver, and study site (adjusted ?: 0.84, 95% CI 0.26-1.42, P = 0.005). This association was attenuated by the addition of literacy (adjusted ?: 0.66, 95% CI 0.11-1.21, P = 0.02) or numeracy (adjusted ?: 0.50, 95% CI -0.04-1.04, P = 0.07) into the model. There was no significant association between acculturation and up-to-date child immunizations or a weight status of overweight/obese. Lower acculturation was associated with worse health literacy and diminished ability to perform child health-related skills. Literacy and numeracy skills attenuated the association between acculturation and child health skills. These associations may help to explain some child health disparities in Latino communities.
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Effect of HSV-2 on population-level trends in HIV incidence in Uganda between 1990 and 2007.
Trop. Med. Int. Health
PUBLISHED: 09-11-2013
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To assess the long-term effects of population-level HSV-2 infection on HIV incidence.
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High-dose interleukin-2: is it still indicated for melanoma and RCC in an era of targeted therapies?
Oncology (Williston Park, N.Y.)
PUBLISHED: 08-28-2013
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Immunotherapy with interleukin-2 (IL-2) has been the mainstay of systemic therapy for advanced kidney cancer and melanoma. Although IL-2 treatment is limited to healthy patients, a select group of these patients have derived substantial, durable benefit from it-in some translating into cures with no ongoing therapy or chronic toxicity. Over the past 10 years, insights into the biology of renal cell carcinoma and into key signaling mechanisms in melanoma, and growth in our understanding of immune checkpoints, have led to the development and approval of targeted and immune-modulatory therapeutic options with clinically relevant benefit. Our improved understanding of the relationship between the host environment, immune system, and malignancy has helped identify compounds and therapies that are changing the way we think about cancer and our approach to cancer therapeutics. While the newer options may be applicable to most patients, durable responses measured in years are rare. In this review, we examine the currently approved options available for these disease processes, including the newer agents and selected combinatorial approaches under investigation, and we attempt to identify the role of high-dose IL-2 in the context of current clinical practice.
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The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma.
Nat Rev Clin Oncol
PUBLISHED: 08-27-2013
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Immunotherapy is associated with durable clinical benefit in patients with melanoma. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA. To achieve this goal, the Society for Immunotherapy of Cancer sponsored a panel of melanoma experts--including physicians, nurses, and patient advocates--to develop a consensus for the clinical application of tumour immunotherapy for patients with melanoma. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development. A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel. This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. From the peer-reviewed literature the consensus panel identified a role for interferon-?2b, pegylated-interferon-?2b, interleukin-2 (IL-2) and ipilimumab in the clinical management of melanoma. Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted.
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Zebrafish cancer: the state of the art and the path forward.
Nat. Rev. Cancer
PUBLISHED: 08-24-2013
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The zebrafish is a recent addition to animal models of human cancer, and studies using this model are rapidly contributing major insights. Zebrafish develop cancer spontaneously, after mutagen exposure and through transgenesis. The tumours resemble human cancers at the histological, gene expression and genomic levels. The ability to carry out in vivo imaging, chemical and genetic screens, and high-throughput transgenesis offers a unique opportunity to functionally characterize the cancer genome. Moreover, increasingly sophisticated modelling of combinations of genetic and epigenetic alterations will allow the zebrafish to complement what can be achieved in other models, such as mouse and human cell culture systems.
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Firearms and suicide in the United States: is risk independent of underlying suicidal behavior?
Am. J. Epidemiol.
PUBLISHED: 08-23-2013
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On an average day in the United States, more than 100 Americans die by suicide; half of these suicides involve the use of firearms. In this ecological study, we used linear regression techniques and recently available state-level measures of suicide attempt rates to assess whether, and if so, to what extent, the well-established relationship between household firearm ownership rates and suicide mortality persists after accounting for rates of underlying suicidal behavior. After controlling for state-level suicide attempt rates (2008-2009), higher rates of firearm ownership (assessed in 2004) were strongly associated with higher rates of overall suicide and firearm suicide, but not with nonfirearm suicide (2008-2009). Furthermore, suicide attempt rates were not significantly related to gun ownership levels. These findings suggest that firearm ownership rates, independent of underlying rates of suicidal behavior, largely determine variations in suicide mortality across the 50 states. Our results support the hypothesis that firearms in the home impose suicide risk above and beyond the baseline risk and help explain why, year after year, several thousand more Americans die by suicide in states with higher than average household firearm ownership compared with states with lower than average firearm ownership.
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Reviewing the evidence for advanced dressings.
Nurs Stand
PUBLISHED: 08-08-2013
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The principles of moist wound healing have become widely accepted since the seminal work of George Winter in the 1960s. In the subsequent 50 years, many publications have extolled the clinical value of modern or advanced wound dressings. This article reviews the findings of two studies arguing that the benefits of advanced wound care products, which are based largely on th principles of moist wound healing, cannot be justified in terms of healing outcomes or cost effectiveness. These studies have the potential to affect clinical practice and decision making, and the article highlights the importance of analysing and interpreting the findings of such studies cautiously.
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Quantification of aortic stiffness using MR Elastography and its comparison to MRI-based pulse wave velocity.
J Magn Reson Imaging
PUBLISHED: 07-29-2013
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To determine the correlation in abdominal aortic stiffness obtained using magnetic resonance elastography (MRE) (?MRE ) and MRI-based pulse wave velocity (PWV) shear stiffness (?PWV ) estimates in normal volunteers of varying age, and also to determine the correlation between ?MRE and ?PWV .
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A health literate approach to the prevention of childhood overweight and obesity.
Patient Educ Couns
PUBLISHED: 07-24-2013
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To describe a systematic assessment of patient educational materials for the Growing Right Onto Wellness (GROW) trial, a childhood obesity prevention study targeting a low health literate population.
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Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis.
Development
PUBLISHED: 07-04-2013
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Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRAS(G12D) expression at different stages during muscle development. Several zebrafish promoters were used, including the cdh15 and rag2 promoters, which drive gene expression in early muscle progenitors, and the mylz2 promoter, which is expressed in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish developed tumors that displayed an inability to complete muscle differentiation as determined by histological appearance and gene expression analyses. By contrast, mylz2:KRAS(G12D) tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma in terms of gene expression. mylz2:KRAS(G12D) fish showed significantly improved survival compared with cdh15:KRAS(G12D) and rag2:KRAS(G12D) fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogenic KRAS(G12D) expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.
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Microdeformation in wound healing.
Wound Repair Regen
PUBLISHED: 06-06-2013
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Mechanical forces greatly influence cellular organization and behavior. Cells respond to applied stress by changes in form and composition until a suitable state is reestablished. However, without any mechanical stimuli cells stop proliferating, discontinue migration, go into cell-cycle arrest, and eventually die. Hence, one can assume that pathologies closely depending on cell migration like cancer or atherosclerosis might be governed by biophysical parameters. Moreover, mechanical cues will have fundamental effects in wound healing. Especially negative pressure wound therapy has the potential to endorse wound healing by induction of both macrodeformation (wound contraction) and microdeformation (tissue reactions at microscopic level). So far, the capacity for researchers to study the link between mechanical stimulation and biological response has been limited by the lack of instrumentation capable of stimulating the tissue in an appropriate manner. However, first reports on application of micromechanical forces to wounds elucidate the roles of cell stretch, substrate stiffness, and tissue deformation during cell proliferation and differentiation. This review deals with their findings and tries to establish a link between the current knowledge and the questions that are essential to clinicians in the field: What is the significance of mirodeformations for wound healing? Does "dead space" impede propagation of mechanical cues? How can microdeformations induce cell proliferation? What role do fibroblasts, myofibroblasts, and mesenchymal stem cells play in chronic wounds with regard to micromechanical forces?
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Transmission potential of Rift Valley fever virus over the course of the 2010 epidemic in South Africa.
Emerging Infect. Dis.
PUBLISHED: 06-06-2013
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A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (Re) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain Re below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.
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The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.
Genome Biol.
PUBLISHED: 06-04-2013
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Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process.
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Heterosexual HIV-1 infectiousness and antiretroviral use: systematic review of prospective studies of discordant couples.
Epidemiology
PUBLISHED: 06-01-2013
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Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings.
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Identification of the zebrafish maternal and paternal transcriptomes.
Development
PUBLISHED: 05-29-2013
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Transcription is an essential component of basic cellular and developmental processes. However, early embryonic development occurs in the absence of transcription and instead relies upon maternal mRNAs and proteins deposited in the egg during oocyte maturation. Although the early zebrafish embryo is competent to transcribe exogenous DNA, factors present in the embryo maintain genomic DNA in a state that is incompatible with transcription. The cell cycles of the early embryo titrate out these factors, leading to zygotic transcription initiation, presumably in response to a change in genomic DNA chromatin structure to a state that supports transcription. To understand the molecular mechanisms controlling this maternal to zygotic transition, it is important to distinguish between the maternal and zygotic transcriptomes during this period. Here we use exome sequencing and RNA-seq to achieve such discrimination and in doing so have identified the first zygotic genes to be expressed in the embryo. Our work revealed different profiles of maternal mRNA post-transcriptional regulation prior to zygotic transcription initiation. Finally, we demonstrate that maternal mRNAs are required for different modes of zygotic transcription initiation, which is not simply dependent on the titration of factors that maintain genomic DNA in a transcriptionally incompetent state.
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Adjuvant dexamethasone for bupivacaine sciatic and ankle blocks: results from 2 randomized placebo-controlled trials.
Reg Anesth Pain Med
PUBLISHED: 05-24-2013
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Dexamethasone as a local anesthetic adjuvant has been shown to prolong the time to first postoperative pain and improve postoperative analgesia following upper-limb brachial plexus block. However, the lack of systemically administered dexamethasone in controls makes interpretation of previous studies difficult. We performed 2 prospective, randomized, double-blind, placebo-controlled trials to test whether the addition of dexamethasone 8 mg to bupivacaine for sciatic and ankle blocks prolongs block duration, improving postoperative analgesia.
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Virtual environments using video capture for social phobia with psychosis.
Cyberpsychol Behav Soc Netw
PUBLISHED: 05-09-2013
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A novel virtual environment (VE) system was developed and used as an adjunct to cognitive behavior therapy (CBT) with six socially anxious patients recovering from psychosis. The novel aspect of the VE system is that it uses video capture so the patients can see a life-size projection of themselves interacting with a specially scripted and digitally edited filmed environment played in real time on a screen in front of them. Within-session process outcomes (subjective units of distress and belief ratings on individual behavioral experiments), as well as patient feedback, generated the hypothesis that this type of virtual environment can potentially add value to CBT by helping patients understand the role of avoidance and safety behaviors in the maintenance of social anxiety and paranoia and by boosting their confidence to carry out "real-life" behavioral experiments.
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2013 ACCF/ACR/ASE/ASNC/SCCT/SCMR appropriate utilization of cardiovascular imaging in heart failure: an executive summary: a joint report of the ACR Appropriateness Criteria ® Committee and the ACCF Appropriate Use Criteria Task Force.
J Am Coll Radiol
PUBLISHED: 05-01-2013
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The ACR and the American College of Cardiology Foundation (ACCF) developed a joint process for determining the appropriate utilization (AU) of cardiovascular imaging modalities in heart failure (HF). This report represents an executive summary of the AU document which was aimed at critically and systematically creating, reviewing, and categorizing clinical situations where physicians order or use imaging tests for patients with suspected, incompletely characterized, or known HF.
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Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth.
PLoS Comput. Biol.
PUBLISHED: 05-01-2013
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It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing), which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.
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Potential roles of adenosine deaminase-2 in diabetic retinopathy.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-30-2013
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The early activation of microglia that induces retinal inflammation in DR may serve as a target for therapeutic intervention of DR. Our demonstration that retinal inflammation is attenuated via adenosine receptor A(2A)AR supports the hypothesis that a mechanism to maintain extracellular concentrations of adenosine important in normal physiology is impaired in DR. Extracellular concentrations of adenosine are regulated by the interplay of equiliberative nucleoside transporter (ENT)s with enzymes of adenosine metabolism including adenosine deaminase-1 (ADA1), adenosine kinase (AK) and CD73. In the vertebrates but not rodents, a macrophage-associated ADA2 is identified. The role of ADA2 is, therefore, understudied as the sequencing probes or antibodies to mouse ADA2 are not available. We identified increased ADA2 expression and activity in human and porcine retinas with diabetes, and in Amadori glycated albumin (AGA)- or hyperglycemia-treated porcine and human microglia. In rodent as well as porcine cells, modulation of TNF-? release is mediated by A(2A)AR. Quantitative analysis of normal and diabetic porcine retinas reveals that while the expression levels of ADA2, A2AAR, ENT1, TNF-? and MMP9 are increased, the levels of AK are reduced during inflammation as an endogenous protective mechanism. To determine the role of ADA2, we found that AGA induces ADA2 expression, ADA2 activity and TNF-? release, and that TNF-? release is blocked by ADA2-neutralizing antibody or ADA2 siRNA, but not by scrambled siRNA. These results suggest that retinal inflammation in DR is mediated by ADA2, and that the anti-inflammatory activity of A(2A)AR signaling is impaired in diabetes due to increased ADA2 activity.
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Bundled payments for care improvement initiative: the next evolution of payment formulations: AAHKS Bundled Payment Task Force.
J Arthroplasty
PUBLISHED: 04-18-2013
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The Patient Protection and Affordable Care Act contains a number of provision for improving the delivery of healthcare in the United States, among the most impactful of which may be the call for modifications in the packaging of and payment for care that is bundled into episodes. The move away from fee for service payment models to payment for coordinated care delivered as comprehensive episodes is heralded as having great potential to enhance quality and reduce cost, thereby increasing the value of the care delivered. This effort builds on the prior experience around delivering care for arthroplasty under the Acute Care Episode Project and offers extensions and opportunities to modify the experience moving forward. Total hip and knee arthroplasties are viewed as ideal treatments to test the effectiveness of this payment model. Providers must learn the nuances of these modified care delivery concepts and evaluate whether their environment is conducive to success in this arena. This fundamental shift in payment for care offers both considerable risk and tremendous opportunity for physicians. Acquiring an understanding of the recent experience and the determinants of future success will best position orthopaedic surgeons to thrive in this new environment. Although this will remain a dynamic exercise for some time, early experience may enhance the chances for long term success, and physicians can rightfully lead the care delivery redesign process.
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2013 appropriate utilization of cardiovascular imaging: a methodology for the development of joint criteria for the appropriate utilization of cardiovascular imaging by the American College of Cardiology Foundation and American College of Radiology.
J Am Coll Radiol
PUBLISHED: 04-15-2013
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The American College of Radiology (ACR) and the American College of Cardiology Foundation (ACCF) have jointly developed a method to define appropriate utilization of cardiovascular imaging. The primary role of this method is to create a series of documents to define the utility of cardiovascular imaging procedures in relation to specific clinical questions, with the aim of defining what, if any, imaging tests are indicated to help to determine diagnosis, treatment, or outcome. The methodology accomplishes this aim through the application of systematic evidence reviews integrated with expert opinion by means of a rigorous Delphi process. By obtaining broad input during the development process from radiologists, cardiologists, primary care physicians, and other stakeholders, these documents are intended to provide practical evidence-based guidance to ordering providers, imaging laboratories, interpreting physicians, patients, and policymakers as to optimal cardiovascular imaging utilization. This document details the history, rationale, and methodology for developing these joint documents for appropriate utilization of cardiovascular imaging.
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Reflective accounts of psychiatry in Australasia, 1963-2000.
Australas Psychiatry
PUBLISHED: 04-10-2013
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To provide reflective accounts of psychiatry through the first four decades of the existence of the Royal Australian and New Zealand College of Psychiatrists (RANZCP).
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A chemoenzymatic total synthesis of the protoilludane aryl ester (+)-armillarivin.
Org. Lett.
PUBLISHED: 04-03-2013
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The title natural product, 1, has been synthesized in 20 steps from the enantiomerically pure cis-1,2-dihydrocatechol 2, itself obtained through the whole-cell biotransformation of toluene. The pivotal steps in the reaction sequence involve a Diels-Alder cycloaddition reaction between diene 2 and cyclopentenone (3) and the photochemically promoted 1,3-acyl rearrangement of the bicyclo[2.2.2]oct-4-en-1-one 20 derived from the cycloadduct 4.
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2013 appropriate utilization of cardiovascular imaging: a methodology for the development of joint criteria for the appropriate utilization of cardiovascular imaging by the American College of Cardiology Foundation and American College of Radiology.
J. Am. Coll. Cardiol.
PUBLISHED: 03-05-2013
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The American College of Radiology (ACR) and the American College of Cardiology Foundation (ACCF) have jointly developed a method to define appropriate utilization of cardiovascular imaging. The primary role of this method is to create a series of documents to define the utility of cardiovascular imaging procedures in relation to specific clinical questions, with the aim of defining what, if any, imaging tests are indicated to help to determine diagnosis, treatment, or outcome. The methodology accomplishes this aim through the application of systematic evidence reviews integrated with expert opinion by means of a rigorous Delphi process. By obtaining broad input during the development process from radiologists, cardiologists, primary care physicians, and other stakeholders, these documents are intended to provide practical evidence-based guidance to ordering providers, imaging laboratories, interpreting physicians, patients, and policymakers as to optimal cardiovascular imaging utilization. This document details the history, rationale, and methodology for developing these joint documents for appropriate utilization of cardiovascular imaging.
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