Concept for a Satellite-Based Advanced Air Traffic Management System : Volume 7. System Cost.

DOT National Transportation Integrated Search

1973-02-01

The volume presents estimates of the federal government and user costs for the Satellite-Based Advanced Air Traffic Management System and the supporting rationale. The system configuration is that presented in volumes II and III. The cost estimates a...

48 CFR 7.105 - Contents of written acquisition plans.

Code of Federal Regulations, 2011 CFR

2011-10-01

... appropriate, discuss the cost model used to develop life-cycle-cost estimates. (ii) Design-to-cost. Describe the design-to-cost objective(s) and underlying assumptions, including the rationale for quantity... of stimulating industry involvement during design and development in recommending the most...

48 CFR 7.105 - Contents of written acquisition plans.

Code of Federal Regulations, 2012 CFR

2012-10-01

... appropriate, discuss the cost model used to develop life-cycle-cost estimates. (ii) Design-to-cost. Describe the design-to-cost objective(s) and underlying assumptions, including the rationale for quantity... of stimulating industry involvement during design and development in recommending the most...

48 CFR 7.105 - Contents of written acquisition plans.

Code of Federal Regulations, 2013 CFR

2013-10-01

... appropriate, discuss the cost model used to develop life-cycle-cost estimates. (ii) Design-to-cost. Describe the design-to-cost objective(s) and underlying assumptions, including the rationale for quantity... of stimulating industry involvement during design and development in recommending the most...

Media of Technological Revolution, Part II

ERIC Educational Resources Information Center

Georgetown Law Journal, 1972

1972-01-01

An overview of the development of electronic media. Governance of television both as entertainment and journalism and its relationship with broadcast advertising is discussed. Cable television, its potential for the future, and how the Federal Communications Commission must develop a new regulatory rationale to deal with new problems are…

40 CFR 798.5200 - Mouse visible specific locus test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

40 CFR 798.5200 - Mouse visible specific locus test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

40 CFR 798.5200 - Mouse visible specific locus test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

40 CFR 798.5200 - Mouse visible specific locus test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

40 CFR 798.5200 - Mouse visible specific locus test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... control groups. (4) Control groups—(i) Concurrent controls. The use of positive or spontaneous controls is... control groups. (ii) Test chemical vehicle, doses used and rationale for dose selection, toxicity data... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5200 Mouse...

Personal Educational Tools (PETs) for Type II Learning

ERIC Educational Resources Information Center

Christensen, Rhonda; Overall, Theresa; Knezek, Gerald

2006-01-01

This article introduces the concept of Personal Educational Tools (PETs) and places these tools within the context of existing rationales for using technology for teaching, learning, and instruction. An identification of the distinguishing characteristics of these devices is followed by the conjecture that these types of classifying…

40 CFR 90.107 - Application for certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... kit installed will meet each emission standard throughout its useful life (the rationale for this...+NOX). (ii) Provide the applicable useful life as determined under § 90.105; (12) A statement... constitutes service on you or any of your officers or employees for any action by EPA or otherwise by the...

76 FR 61761 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... retained up to 3 years after the customer relationship ends. * * * * * 6. Records related to inquiries and.... These modifications reflect the changes that have been made in providing alternate access to customers... products and services when and where its customers want them. II. Rationale for Changes to USPS Privacy Act...

Humanities II: Man and Revolution.

ERIC Educational Resources Information Center

Stanton School District, Wilmington, DE.

"Man and Revolution," the second syllabus in a sequential program, provides 11th grade students with a humanities course that deals heavily in political theory. The rationale, objectives, guidelines, methods, and arrangement are the same as those described in SO 004 030. The introductory unit, followed by further units, helps students define and…

The Acid Rain Game.

ERIC Educational Resources Information Center

Rakow, Steven J.; Glenn, Allen

1982-01-01

Provides rationale for and description of an acid rain game (designed for two players), a problem-solving model for elementary students. Although complete instructions are provided, including a copy of the game board, the game is also available for Apple II microcomputers. Information for the computer program is available from the author.…

Selecting measures to prevent deleterious alkali-silica reaction in concrete : rationale for the AASHTO PP65 prescriptive approach.

DOT National Transportation Integrated Search

2012-10-01

PP65-11 provides two approaches for selecting preventive measures: (i) a performance approach based on laboratory testing, and (ii) a prescriptive approach based on a consideration of the reactivity of the aggregate, type and size of structure, expos...

DEVELOPMENT OF PROTEIN PROFILE TECHNOLOGY TO EVALUATE ECOLOGICAL EFFECTS OF ENVIRONMENTAL CHEMICALS USING A SMALL FISH MODEL

EPA Science Inventory

The rationale for this research is: i) Protein expression changes with life stage, disease, tissue type and environmental stressors; ii) Technology allows rapid analysis of large numbers of proteins to provide protein expression profiles; iii) Protein profiles are used as specifi...

Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moderate obesity.

PubMed

Ali, Khawla F; Shukla, Alpana P; Aronne, Louis J

2016-01-01

Naltrexone-bupropion is a recently approved drug combination for chronic weight management. In this article, we discuss the rationale for its use as a combination followed by a comprehensive review of safety and efficacy data from major preclinical, phase II and III clinical trials.

Deep Impact Delta II Launch Vehicle Cracked Thick Film Coating on Electronic Packages Technical Consultation Report

NASA Technical Reports Server (NTRS)

Cameron, Kenneth D.; Kichak, Robert A.; Piascik, Robert S.; Leidecker, Henning W.; Wilson, Timmy R.

2009-01-01

The Deep Impact spacecraft was launched on a Boeing Delta II rocket from Cape Canaveral Air Force Station (CCAFS) on January 12, 2005. Prior to the launch, the Director of the Office of Safety and Mission Assurance (OS&MA) requested the NASA Engineering and Safety Center (NESC) lead a team to render an independent opinion on the rationale for flight and the risk code assignments for the hazard of cracked Thick Film Assemblies (TFAs) in the E-packages of the Delta II launch vehicle for the Deep Impact Mission. The results of the evaluation are contained in this report.

Travelling without a helmet: tourists' vulnerabilities and responses to disasters in Indonesia.

PubMed

Rindrasih, Erda; Hartmann, Thomas; Witte, Patrick; Spit, Tejo; Zoomers, Annelies

2018-03-13

Tourists are particularly vulnerable when natural disasters occur in regions that they are visiting. It is assumed that they lack awareness and understanding of the actions that they need to take in such circumstances. This study examines the responses of tourists in times of disaster, building on empirical data collected through large-scale surveys conducted in Bali and Yogyakarta, Indonesia, in 2015. Both are important tourist destinations in the country that have suffered major disasters in recent years. The different types of responses to these events are framed using a grid/group analysis stemming from cultural theory. The study resulted in three key findings: (i) current disaster management planning largely follows a single rationale; (ii) tourists are not a homogeneous group, but rather a complex, diverse, and dynamic body of stakeholders; and (iii) the focus of disaster management planning should shift from a single rationale to a polyrational methodology. Disaster managers need to consider, therefore, these different aspects in the context of preparedness. © 2018 The Author(s). Disasters © Overseas Development Institute, 2018.

Effects of Role and Assignment Rationale on Attitudes Formed During Peer Tutoring

PubMed Central

Bierman, Karen Linn; Furman, Wyndol

2012-01-01

This study examined the role of contextual factors, such as assignment rationale, on the attitudinal effects of peer tutoring. Fourth-grade children engaged in brief tutoring experiences as either a tutor or tutee. Subjects received four rationales for being selected as tutor or tutee: (a) a competence rationale, (b) a physical characteristic rationale, (c) a chance rationale, or (d) no rationale. As predicted, tutors had more positive attitudes than tutees when they had been given a competence or physical characteristic rationale but not when the tutors were provided a chance rationale or no rationale. Additionally, the tutors’ and tutees’ attitudes were enhanced when no rationale was provided. Results are discussed in terms of their implications for a role-theory analysis of tutoring and their implications for applied programs. PMID:23946549

Effects of Role and Assignment Rationale on Attitudes Formed During Peer Tutoring.

PubMed

Bierman, Karen Linn; Furman, Wyndol

1981-02-01

This study examined the role of contextual factors, such as assignment rationale, on the attitudinal effects of peer tutoring. Fourth-grade children engaged in brief tutoring experiences as either a tutor or tutee. Subjects received four rationales for being selected as tutor or tutee: (a) a competence rationale, (b) a physical characteristic rationale, (c) a chance rationale, or (d) no rationale. As predicted, tutors had more positive attitudes than tutees when they had been given a competence or physical characteristic rationale but not when the tutors were provided a chance rationale or no rationale. Additionally, the tutors' and tutees' attitudes were enhanced when no rationale was provided. Results are discussed in terms of their implications for a role-theory analysis of tutoring and their implications for applied programs.

76 FR 39477 - Revisions and Additions to Motor Vehicle Fuel Economy Label

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... C. Rationale for Revising the Label D. Market Research II. Statutory Provisions and Legal Authority.... Public Participation and Comment A. Energy Metrics B. Rating Systems C. Form of the Ratings D. Fuel... comment on an alternative Label 3 that retained the more traditional layout of Label 2 but used different...

76 FR 71450 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; Determination of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

..., Region III, 1650 Arch Street, Philadelphia, Pennsylvania 19103. FOR FURTHER INFORMATION CONTACT: Asrah... EPA taking? II. What is the effect of this action? III. Statutory and Executive Order Reviews I. What... discussion of the rationale behind this determination and the effect of the determination were included in...

Tarawa Landing: Proving Ground for Pacific Victory.

ERIC Educational Resources Information Center

Fox, Thomas

1990-01-01

Points out the importance of the Tarawa landing in the Gilbert Islands during World War II, and recommends teaching about the event. Provides detailed analysis of the November 21-24, 1943, amphibious assault by U.S. Marines. Examines the rationale for the location, timing, and type of attack. Identifies key personnel. Includes intelligence map of…

PATHS - Providing Appropriate Training in Head Start: A Grantee Guide.

ERIC Educational Resources Information Center

Riley, Mary Tom; And Others

Designed for Head Start grantees, this book provides training guidelines for improving Head Start staff competency. Chapter I offers a rationale for staff training activities, while chapter II characterizes the Head Start trainee. Chapter III addresses assessment of training needs on program and staff levels. The development of a training plan is…

Futures Unlimited: Teaching About Worlds to Come. Bulletin 59.

ERIC Educational Resources Information Center

Fitch, Robert M.; Svengalis, Cordell, M.

A theoretical framework and suggestions for teaching about the future at the secondary level are presented. Seven chapters comprise the document. Chapter I examines the nature of and approach to futurism and explores ideas of European and American futurists. Chapter II presents a rationale, characteristics of futures education, outlines of courses…

A serious video game to increase fruit and vegetable consumption among elementary aged youth (Squire's Quest! II): Rationale, design, and methods

USDA-ARS?s Scientific Manuscript database

Youths eat fewer fruits and vegetables than recommended. Effective methods are needed to increase and maintain their fruit and vegetable consumption. Goal setting has been an effective behavior change procedure among adults, but has had limited effectiveness among youths. Implementation intentions a...

Chemoradiation in elderly esophageal cancer patients: rationale and design of a phase I/II multicenter study (OSAGE).

PubMed

Servagi-Vernat, Stéphanie; Créhange, Gilles; Bonnetain, Franck; Mertens, Cécile; Brain, Etienne; Bosset, Jean François

2017-07-13

The management of elderly patients with cancer is a therapeutic challenge and a public health problem. Definitive chemoradiotherapy (CRT) is an accepted standard treatment for patients with locally advanced esophageal cancer who cannot undergo surgery. However, there are few reports regarding tolerance to CRT in elderly patients. We previously reported results for CRT in patients aged ≥75 years. Following this first phase II trial, we propose to conduct a phase I/II study to evaluate the combination of carboplatin and paclitaxel, with concurrent RT in unresectable esophageal cancer patients aged 75 years or older. This prospective multicenter phase I/II study will include esophageal cancer in patients aged 75 years or older. Study procedures will consist to determinate the tolerated dose of chemotherapy (Carboplatin, paclitaxel) and of radiotherapy (41.4-45 and 50.4 Gy) in the phase I. Efficacy will be assessed using a co-primary endpoint encompassing health related quality of life and the progression-free survival in the phase II with the dose recommended of CRT in the phase I. This geriatric evaluation was defined by the French geriatric oncology group (GERICO). This trial has been designed to assess the tolerated dose of CRT in selected patient aged 75 years or older. Clinicaltrials.gov ID: NCT02735057 . Registered on 18 March 2016.

Estimation of the Operating Characteristics when the Test Information of the Old Test is not Constant II: Simple Sum Procedure of the Conditional P.D.F. Approach/Normal Approach Method Using Three Subtests of the Old Test. Research Report 80-4.

ERIC Educational Resources Information Center

Samejima, Fumiko

The rationale behind the method of estimating the operating characteristics of discrete item responses when the test information of the Old Test is not constant was presented previously. In the present study, two subtests of the Old Test, i.e. Subtests 1, and 2, each of which has a different non-constant test information function, are used in…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonnefont, J.P.; Cepanec, C.; Leroux, J.P.

Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibilitymore » of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.« less

Use of a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer: development and preliminary evaluation.

PubMed

Miles, A; Chronakis, I; Fox, J; Mayer, A

2017-03-24

To develop a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer, and examine perceived usefulness, acceptability and areas for improvement of the DA. Mixed methods. Single outpatient oncology department in central London. Consecutive recruitment of 13 patients with stage II colorectal cancer, 12 of whom completed the study. Inclusion criteria were: age >18 years; complete resection for stage II adenocarcinoma of the colon or rectum; patients within 14-56 days after surgery; no contraindication to adjuvant chemotherapy; able to give written informed consent. Exclusion criterion: previous chemotherapy. Patient perceived usefulness (assessed by the PrepDM questionnaire) and acceptability of the DA. PrepDM scores, measuring the perceived usefulness of the DA in preparing the patient to communicate with their doctor and make a health decision, were above those reported in other patient groups. Patient acceptability scores were also high; however, interviews showed that there was evidence of a lack of understanding of key information among some patients, in particular their baseline risk of recurrence, the net benefit of combination chemotherapy and the rationale for having chemotherapy when cancer had apparently gone. Patients found the DA acceptable and useful in supporting their decision about whether or not to have adjuvant chemotherapy. Suggested improvements for the DA include: sequential presentation of treatment options (eg, no treatment vs 1 drug, 1 drug vs 2 drugs) to enhance patient understanding of the difference between combination and single therapy, diagrams to help patients understand the rationale for chemotherapy to prevent a recurrence and inbuilt checks on patient understanding of baseline risk of recurrence and net benefit of chemotherapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS): rationale, design, and methods.

PubMed

Apers, Silke; Kovacs, Adrienne H; Luyckx, Koen; Alday, Luis; Berghammer, Malin; Budts, Werner; Callus, Edward; Caruana, Maryanne; Chidambarathanu, Shanthi; Cook, Stephen C; Dellborg, Mikael; Enomoto, Junko; Eriksen, Katrine; Fernandes, Susan M; Jackson, Jamie L; Johansson, Bengt; Khairy, Paul; Kutty, Shelby; Menahem, Samuel; Rempel, Gwen; Sluman, Maayke A; Soufi, Alexandra; Thomet, Corina; Veldtman, Gruschen; Wang, Jou-Kou; White, Kamila; Moons, Philip

2015-01-20

Data on patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Better understanding of PROs and their differences across cultural and geographic barriers can best be accomplished via international studies using uniform research methods. The APPROACH-IS consortium (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study) was created for this purpose and investigates PROs in adults with CHD worldwide. This paper outlines the project rationale, design, and methods. APPROACH-IS is a cross-sectional study. The goal is to recruit 3500-4000 adults with CHD from 15 countries in five major regions of the world (Asia, Australia, Europe, North and South America). Self-report questionnaires are administered to capture information on PRO domains: (i) perceived health status (12-item Short-form Health Survey & EuroQOL-5D); (ii) psychological functioning (Hospital Anxiety and Depression Scale); (iii) health behaviors (Health-Behavior Scale-Congenital Heart Disease); and (iv) quality of life (Linear Analog Scale & Satisfaction With Life Scale). Additionally, potential explanatory variables are assessed: (i) socio-demographic variables; (ii) medical history (chart review); (iii) sense of coherence (Orientation to Life Questionnaire); and (iv) illness perceptions (Brief Illness Perception Questionnaire). Descriptive analyses and multilevel models will examine differences in PROs and investigate potential explanatory variables. APPROACH-IS represents a global effort to increase research understanding and capacity in the field of CHD, and will have major implications for patient care. Results will generate valuable information for developing interventions to optimize patients' health and well-being. ClinicalTrials.gov: NCT02150603. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mouse models expressing human carcinoembryonic antigen (CEA) as a transgene: Evaluation of CEA-based cancer vaccines

PubMed Central

Hance, Kenneth W.; Zeytin, Hasan E.; Greiner, John W.

2010-01-01

In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a Mr 180–200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines. PMID:15888344

INFOSAM: A Sample Database Management System.

DTIC Science & Technology

1981-12-01

PROGRAM ELEMENT. PROJECT, TASA Sloan School of Management AREA WORK UNIT NUMBERS Massachusetts Institute of Technology Cambridge, MA 02139 II...96 NSETCAT .. ............................. 96 Inter -level Communication Databases .... 99 DEEAR ...................... 100 DVAR...Conceptual level, and the External level. The Inter - nal level represents a union of Hsu’s proposed Unary and Binary levels. The rationale for combining the

Competency-Based Adult Education Classroom Management Guide for Adult Basic Education Curriculum (Level II, 5-8).

ERIC Educational Resources Information Center

Singer, Elizabeth

This Competency-Based Adult Basic Education (CBABE) Classroom Management Guide was developed to aid the Adult Basic Education (ABE) facilitator in implementing a model CBABE Level 5-8 curriculum. First, introductory material provides background on the CBABE project at Brevard Community College (Florida) and the rationale for the development of the…

Putting It All Together: A Model for Parish Educational Policymaking. Second Edition.

ERIC Educational Resources Information Center

Harper, Mary-Angela

The rationale of shared responsibility by the hierarchy and the laity for directing Catholic school and non-school religious educational programs is clearly present in the Vatican Council II documents, which state that members of the laity should be involved in all decisions affecting their lives and that appropriate structures should be…

Technical Manual for the Conceptual Learning and Development Assessment Series II: Equilateral Triangle. Technical Report No. 434. Reprinted December 1977.

ERIC Educational Resources Information Center

DiLuzio, Geneva J.; And Others

This document accompanies the Conceptual Learning and Development Assessment Series I: Equilateral Triangle, a test constructed to chart the conceptual developemnt of individuals. As a technical manual, it contains information on the rationale, development, standardization, and reliability of the test, as well as essential information and…

The effect of incentive spirometry on chest expansion and breathing work in patients with chronic obstructive airway diseases: comparison of two methods.

PubMed

Ho, S C; Chiang, L L; Cheng, H F; Lin, H C; Sheng, D F; Kuo, H P; Lin, H C

2000-02-01

Chronic obstructive airway diseases (COAD), characterized by mucus hypersecretion, lead to exercise intolerance. Incentive spirometry has been used to prevent postoperative pulmonary atelectasis. To compare the efficacy of two incentive spirometers, Coach (volume-oriented) and Triflo (flow-oriented), in the work of breathing in COAD patients, 22 patients were randomized in this study: 12 patients (Triflo-II group) initially used Triflo-II for 10 minutes and then Coach for the same period. In contrast, the Coach group, including 10 patients, started with Coach followed by Triflo-II. After receiving incentive spirometry, lung expansion and work of breathing were assessed. Patients in the Coach group significantly increased chest wall expansion (p = 0.041), as compared with patients using Triflo-II. Similarly, there was also a significantly increased abdominal wall expansion in the Coach group (p = 0.0056), compared with that in the Triflo-II group. The need of accessory muscle assistance for breathing in the Coach group was significantly less than in the Triflo-II group (p = 0.047). It was easier for patients in the Coach group to start a breath (p = 0.0058) than for those in the Triflo-II group. For the entire group, 17 patients (77.3%) preferred Coach to assist their breathing, and only 4 patients (18.2%) favored Triflo-II. COAD patients achieved a larger expansion of the chest and abdomen with a Coach device. Our data provide a good rationale for an outcome study on the use of incentive spirometer in COAD patients.

Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design.

PubMed

Wang, Yilong; Lin, Yi; Meng, Xia; Chen, Weiqi; Chen, Guohua; Wang, Zhimin; Wu, Jialing; Wang, Dali; Li, Jianhua; Cao, Yibin; Xu, Yuming; Zhang, Guohua; Li, Xiaobo; Pan, Yuesong; Li, Hao; Liu, Liping; Zhao, Xingquan; Wang, Yongjun

2017-04-01

Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.

78 FR 4307 - Current Good Manufacturing Practice Requirements for Combination Products

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-22

.... Rationale for the Rulemaking B. The Proposed Rule C. The Final Rule II. Comments on the Proposed Rule A. General B. What is the scope of this subpart? (Sec. 4.1) C. How does FDA define key terms and phrases in... Act (the PHS Act) (42 U.S.C. 262). All biological products regulated under the PHS Act meet the...

Evaluating Children's Learning Disabilities with an Apple II Personal Computer or Tempting Poor Learners with an Apple.

ERIC Educational Resources Information Center

Sisson, Lee Hansen; And Others

This paper describes the use of commercially-available software for the Apple Computer to augment diagnostic evaluations of learning disabled children and to enhance "learning to learn" strategies at the application/transfer level of learning. A short rationale discusses levels of evaluation and learning, using a model that synthesizes the ideas…

Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods.

PubMed

Weiland, S K; Björkstén, B; Brunekreef, B; Cookson, W O C; von Mutius, E; Strachan, D P

2004-09-01

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.

Structure, Citizenship, and Professionalism: Exploring Rationale Development as Part of Graduate Education in Social Studies

ERIC Educational Resources Information Center

Hawley, Todd S.; Pifel, A. Robert; Jordan, Adam W.

2012-01-01

This article details an interpretive, qualitative interview study that explored rationales developed by seven social studies graduate students, all experienced teachers, at a large Midwestern university. Interviews revealed three common themes regarding the influence of the rationale development process. The three themes were: providing structure,…

Effects of Providing a Rationale for Learning a Lesson on Students' Motivation and Learning in Online Learning Environments

ERIC Educational Resources Information Center

Shin, Tae Seob

2010-01-01

This study examined whether providing a rationale for learning a particular lesson influences students' motivation and learning in online learning environments. A mixed-method design was used to investigate the effects of two types of rationales (former student vs. instructor rationales) presented in an online introductory educational psychology…

Cargo Movement Operations System (CMOS) System Segment Design Document (Draft) Increment II

DTIC Science & Technology

1990-05-02

and are arranged in page number order. RATIONALE: N/A CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION...NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ] CLOSED [ ] ORIGINATOR CONTROL NUMBER: SSDD-0003 PROGRAM...CMOS. CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ] CLOSED [ 3 ORIGINATOR

Cargo Movement Operations System (CMOS): Revised Preliminary Software Design Document (Applications CSCI), Increment II

DTIC Science & Technology

1991-05-23

background color does not change. CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO ( ] COMMENT DISPOSITION: CONMENT STATUS: OPEN...NO ( ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ) CLOSED [ ] ,$ ...collected on this worksheet and are arranged in page number order. RATIONALE: N/A CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO

Individualized Inservice Teacher Education (Project In-Step). Evaluation Report. Phase III.

ERIC Educational Resources Information Center

Thurber, John C.

This is a report on the third phase of Project IN-STEP, which was intended to develop a viable model for individualized, multi-media in-service teacher education programs. (Phase I and II are reported in ED 033 905, and ED 042 709). The rationale for Phase III was to see if the model could be successfully transferred to an area other than teaching…

Rationales Shaping International Linkages in Higher Education: A Qualitative Case Study of the ASU-ITESM Strategic Alliance

ERIC Educational Resources Information Center

Camacho Lizarraga, Monica Irene

2011-01-01

This qualitative case study examines the rationales of the relationship between Arizona State University (ASU)--an American public research university--and Tecnologico de Monterrey (ITESM), a Mexican private not for profit research university. The focus of the study is to document the different meanings participants attached to the rationales of…

Centrifugal slurry pump wear and hydraulic studies. Phase II report. Experimental studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mistry, D.; Cooper, P.; Biswas, C.

1983-01-01

This report describes the work performed by Ingersoll-Rand Research, Inc., under Phase II, Experimental Studies for the contract entitled, Centrifugal Slurry Pump Wear and Hydraulic Studies. This work was carried out for the US Department of Energy under Contract No. DE-AC-82PC50035. The basic development approach pursued this phase is presented, followed by a discussion on wear relationships. The analysis, which resulted in the development of a mathematical wear model relating pump life to some of the key design and operating parameters, is presented. The results, observations, and conclusions of the experimental investigation on small scale pumps that led to themore » selected design features for the prototype pump are discussed. The material investigation was performed at IRRI, ORNL and Battelle. The rationale for selecting the materials for testing, the test methods and apparatus used, and the results obtained are presented followed by a discussion on materials for a prototype pump. In addition, the prototype pump test facility description, as well as the related design and equipment details, are presented. 20 references, 53 figures, 13 tables.« less

Installation Restoration Program. Phase II. Confirmation/Quantification Stage I.

DTIC Science & Technology

1986-02-24

Drilling and sampling three...borings at Site 8; o Drilling and sampling three borings at Site 11; and o Drilling and sampling three borings at Site 12. The ground water samples...8217-"~~~~~~.."." . " -’ - . .. . ;’ "..-. ’,"",,.- - -".-" - ’ -- -... ... ~ -. . ... ... " " 1 *. Sites Recommended Action Rationale U 8 Drill and sample one background To estimate

CHBPR: ANGIOTENSIN II, INDEPENDENT OF PLASMA RENIN ACTIVITY, CONTRIBUTES TO THE HYPERTENSION OF AUTONOMIC FAILURE

PubMed Central

Arnold, Amy C.; Okamoto, Luis E.; Gamboa, Alfredo; Shibao, Cyndya; Raj, Satish R.; Robertson, David; Biaggioni, Italo

2013-01-01

At least half of primary autonomic failure patients exhibit supine hypertension, despite profound impairments in sympathetic activity. While the mechanisms underlying this hypertension are unknown, plasma renin activity is often undetectable suggesting renin-angiotensin pathways are not involved. However, because aldosterone levels are preserved, we tested the hypothesis that angiotensin II is intact and contributes to the hypertension of autonomic failure. Indeed, circulating angiotensin II was paradoxically increased in hypertensive autonomic failure patients (52±5 pg/ml, n=11) compared to matched healthy controls (27±4 pg/ml, n=10; p=0.002), despite similarly low renin activity (0.19±0.06 versus 0.34±0.13 ng/ml/hr, respectively; p=0.449). To determine the contribution of angiotensin II to supine hypertension in these patients, we administered the AT1 receptor blocker losartan (50 mg) at bedtime in a randomized, double-blind, placebo-controlled study (n=11). Losartan maximally reduced systolic blood pressure by 32±11 mmHg at 6 hours after administration (p<0.05), decreased nocturnal urinary sodium excretion (p=0.0461), and did not worsen morning orthostatic tolerance. In contrast, there was no effect of the captopril on supine blood pressure in a subset of these patients. These findings suggest that angiotensin II formation in autonomic failure is independent of plasma renin activity, and perhaps angiotensin converting enzyme. Furthermore, these studies suggest that elevations in angiotensin II contribute to the hypertension of autonomic failure, and provide rationale for the use of AT1 receptor blockers for treatment of these patients. PMID:23266540

Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.

PubMed

Schaeffer, Edward M; Guzzo, Thomas J; Furge, Kyle A; Netto, George; Westphal, Michael; Dykema, Karl; Yang, Ximing; Zhou, Ming; Teh, Bin Tean; Pavlovich, Christian P

2010-07-01

Aetiology (case series) Level of Evidence 4. To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal. The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy. Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC. This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.

Proposed changes in personality and personality disorder assessment and diagnosis for DSM-5 Part I: Description and rationale.

PubMed

Skodol, Andrew E; Clark, Lee Anna; Bender, Donna S; Krueger, Robert F; Morey, Leslie C; Verheul, Roel; Alarcon, Renato D; Bell, Carl C; Siever, Larry J; Oldham, John M

2011-01-01

A major reconceptualization of personality psychopathology has been proposed for DSM-5 that identifies core impairments in personality functioning, pathological personality traits, and prominent pathological personality types. A comprehensive personality assessment consists of four components: levels of personality functioning, personality disorder types, pathological personality trait domains and facets, and general criteria for personality disorder. This four-part assessment focuses attention on identifying personality psychopathology with increasing degrees of specificity, based on a clinician's available time, information, and expertise. In Part I of this two-part article, we describe the components of the new model and present brief theoretical and empirical rationales for each. In Part II, we will illustrate the clinical application of the model with vignettes of patients with varying degrees of personality psychopathology, to show how assessments might be conducted and diagnoses reached.

Polyether complexes of groups 13 and 14.

PubMed

Swidan, Ala'aeddeen; Macdonald, Charles L B

2016-07-21

Notable aspects of the chemistry of complexes of polyether ligands including crown ethers, cryptands, glycols, glymes, and related polyether ligands with heavier group 13 and 14 elements are reviewed with a focus on results from 2005 to the present. The majority of reported polyether complexes contain lead(ii) and thallium(i) but recent breakthroughs in regard to the preparation of low oxidation state reagents of the lighter congeners have allowed for the generation of complexes containing indium(i), gallium(i), germanium(ii), and even silicon(ii). The important roles of ligand size, donor types, and counter anions in regard to the chemical properties of the polyether complexes is highlighted. A particular focus on the structural aspects of the numerous coordination complexes provides a rationale for some of the spectacular contributions that such compounds have made to Modern Main Group Chemistry.

Data book: Space station/base food system study. Book 3: Study selection rationale sheets

NASA Technical Reports Server (NTRS)

1970-01-01

The supporting rationale sheets are presented which were utilized in the selection and support of the concepts considered in the final phase of the study. Each concept, conceived to fulfill a specific function of the food system, was assessed in terms of the eight critical factors depicted on the rationale sheet. When weighted and totaled, the resulting selection factor was used as a guide in making the final decision.

Rationale for Student Dress Codes: A Review of School Handbooks

ERIC Educational Resources Information Center

Freeburg, Elizabeth W.; Workman, Jane E.; Lentz-Hees, Elizabeth S.

2004-01-01

Through dress codes, schools establish rules governing student appearance. This study examined stated rationales for dress and appearance codes in secondary school handbooks; 182 handbooks were received. Of 150 handbooks containing a rationale, 117 related dress and appearance regulations to students' right to a non-disruptive educational…

A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and Rationale

PubMed Central

Fournié, Guillaume; Høg, Erling; Barnett, Tony; Pfeiffer, Dirk U.; Mangtani, Punam

2017-01-01

Abstract. Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages. PMID:28749769

Attitudes towards Affirmative Action: Effects of Procedural Rationale and Candidates' Qualifications.

ERIC Educational Resources Information Center

Mann, Jeffrey A.; Fasolo, Peter M.

This study examined whether individuals in higher education who are exposed to a hiring rationale based on a diversity value (minority group differences are valuable and should be relevant criteria for employment decisions in higher education) will rate affirmative action as fairer than those exposed to a compensation rationale (minority status is…

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures.

PubMed

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R; Schreiber, Fred; Anderson, Kyle

2012-01-21

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures

PubMed Central

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Connors, Shahnjayla; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Anderson, Kyle

2014-01-01

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention. PMID:24533253

Tobacco control and gender in south-east Asia. Part II: Singapore and Vietnam.

PubMed

Morrow, Martha; Barraclough, Simon

2003-12-01

In the World Health Organization's Western Pacific Region, being born male is the single greatest risk marker for tobacco use. While the literature demonstrates that risks associated with tobacco use may vary according to sex, gender refers to the socially determined roles and responsibilities of men and women, who initiate, continue and quit using tobacco for complex and often different reasons. Cigarette advertising frequently appeals to gender roles. Yet tobacco control policy tends to be gender-blind. Using a broad, gender-sensitivity framework, this contradiction is explored in four Western Pacific countries. Part I of the study presented the rationale, methodology and design of the study, discussed issues surrounding gender and tobacco, and analysed developments in Malaysia and the Philippines (see the previous issue of this journal). Part II deals with Singapore and Vietnam. In all four countries gender was salient for the initiation and maintenance of smoking. Yet, with a few exceptions, gender was largely unrecognized in control policy. Suggestions for overcoming this weakness in order to enhance tobacco control are made.

The Effects of Rationales, Differential Reinforcement, and a Guided Compliance Procedure to Increase Compliance among Preschool Children

ERIC Educational Resources Information Center

Wilder, David A.; Myers, Kristin; Nicholson, Katie; Allison, Janelle; Fischetti, Anthony T.

2012-01-01

Previous research suggests that rationales, or statements describing why a child should comply with a caregiver-delivered instruction, are ineffective at increasing compliance. In the current study, we compared the effects of rationales to a differential reinforcement procedure and a guided compliance procedure. The results indicated that…

Does Ramadan fasting contribute to the increase of peptic ulcer perforations?

PubMed

Kocakusak, A

2017-01-01

Medical treatment has been widely used in peptic ulcer disease, however perforation is a severe complication. The rationale of this study was to evaluate the effect of Islamic Ramadan fasting on peptic ulcer perforation. Patients (No. 2311) who were operated on due to peptic ulcer perforation in a teaching and reference Hospital of a State University from January 1979 to January 2016 were analyzed. Patients were divided into two groups. Group I (No. 1805) included patients who were operated during other periods of the years without Ramadan fasting (396 months), while Group II (No. 506) constituted of patients who were operated on during the fasting periods (36 months). There was no significant difference in the mean ages between the groups (38 vs. 42 years). The mean monthly number of surgical intervention rates was higher in Group II (14.05 vs. 4.55, p < 0.001). There was a statistically significant rise in the number of male patients during Ramadan months (p = 0.0073). While omentoplasty with upper midline laparotomy vs. other surgical methods was significantly more employed in Group II (p = 0.0024), mortality rates were similar as 2.27 and 2.56% in Group I and II, respectively (p > 0.05). We could not detect any seasonal differences, although hot summer days constituted the longest fasting durations (19 hours) in the country. This study suggested that the occurrence of peptic ulcer perforation was significantly high during Ramadan fasting months due to the long fasting periods especially with significant male predominance.

Pesticides and health: a review of evidence on health effects, valuation of risks, and benefit-cost analysis.

PubMed

Tago, Damian; Andersson, Henrik; Treich, Nicolas

2014-01-01

This study presents literature reviews for the period 2000-2013 on (i) the health effects of pesticides and on (ii) preference valuation of health risks related to pesticides, as well as a discussion of the role of benefit-cost analysis applied to pesticide regulatory measures. This study indicates that the health literature has focused on individuals with direct exposure to pesticides, i.e. farmers, while the literature on preference valuation has focused on those with indirect exposure, i.e. consumers. The discussion highlights the need to clarify the rationale for regulating pesticides, the role of risk perceptions in benefit-cost analysis, and the importance of inter-disciplinary research in this area. This study relates findings of different disciplines (health, economics, public policy) regarding pesticides, and identifies gaps for future research.

Weight and Veterans' Environments Study (WAVES) I and II: Rationale, Methods, and Cohort Characteristics.

PubMed

Zenk, Shannon N; Tarlov, Elizabeth; Powell, Lisa M; Wing, Coady; Matthews, Stephen A; Slater, Sandy; Gordon, Howard S; Berbaum, Michael; Fitzgibbon, Marian L

2018-03-01

To present the rationale, methods, and cohort characteristics for 2 complementary "big data" studies of residential environment contributions to body weight, metabolic risk, and weight management program participation and effectiveness. Retrospective cohort. Continental United States. A total of 3 261 115 veterans who received Department of Veterans Affairs (VA) health care in 2009 to 2014, including 169 910 weight management program participants and a propensity score-derived comparison group. The VA MOVE! weight management program, an evidence-based lifestyle intervention. Body mass index, metabolic risk measures, and MOVE! participation; residential environmental attributes (eg, food outlet availability and walkability); and MOVE! program characteristics. Descriptive statistics presented on cohort characteristics and environments where they live. Forty-four percent of men and 42.8% of women were obese, whereas 4.9% of men and 9.9% of women engaged in MOVE!. About half of the cohort had at least 1 supermarket within 1 mile of their home, whereas they averaged close to 4 convenience stores (3.6 for men, 3.9 for women) and 8 fast-food restaurants (7.9 for men, 8.2 for women). Forty-one percent of men and 38.6% of women did not have a park, and 35.5% of men and 31.3% of women did not have a commercial fitness facility within 1 mile. Drawing on a large nationwide cohort residing in diverse environments, these studies are poised to significantly inform policy and weight management program design.

Better exercise adherence after treatment for cancer (BEAT Cancer) study: Rationale, design, and methods

PubMed Central

Rogers, Laura Q.; McAuley, Edward; Anton, Philip M.; Courneya, Kerry S.; Vicari, Sandra; Hopkins-Price, Patricia; Verhulst, Steven; Mocharnuk, Robert; Hoelzer, Karen

2011-01-01

Most breast cancer survivors do not engage in regular physical activity. Our physical activity behavior change intervention for breast cancer survivors significantly improved physical activity and health outcomes post-intervention during a pilot, feasibility study. Testing in additional sites with a larger sample and longer follow-up is warranted to confirm program effectiveness short and longer term. Importantly, the pilot intervention resulted in changes in physical activity and social cognitive theory constructs, enhancing our potential for testing mechanisms mediating physical activity behavior change. Here, we report the rationale, design, and methods for a two-site, randomized controlled trial comparing the effects of the BEAT Cancer physical activity behavior change intervention to usual care on short and longer term physical activity adherence among breast cancer survivors. Secondary aims include examining social cognitive theory mechanisms of physical activity behavior change and health benefits of the intervention. Study recruitment goal is 256 breast cancer survivors with a history of ductal carcinoma in situ or Stage I, II, or IIIA disease who have completed primary cancer treatment. Outcome measures are obtained at baseline, 3 months (i.e., immediately post-intervention), 6 months, and 12 months and include physical activity, psychosocial factors, fatigue, sleep quality, lower extremity joint dysfunction, cardiorespiratory fitness, muscle strength, and waist-to-hip ratio. Confirming behavior change effectiveness, health effects, and underlying mechanisms of physical activity behavior change interventions will facilitate translation to community settings for improving the health and well-being of breast cancer survivors. PMID:21983625

Great River Environmental Action Team (GREAT II). Upper Mississippi River (Guttenberg, Iowa to Saverton, Missouri). Environmental Report. Supplement.

DTIC Science & Technology

1980-12-01

extracted will a!.’, e - , C! C. Rationale for Selected Alternative - This statement ic based upon information contained in the Preliminary Impact...UPPER MI SS ISS--E UCASSTFT EC94190TION 33 The President’s Council on Environmental Quality has established a I National Oil and Hazardous Substance...liasons. The RRT is to provide for efficient, coordinated and effective action to minimize damage from oil and hazardous substances discharges, includ

Cargo Movement Operations System (CMOS). Increment II System Design Document, Final

DTIC Science & Technology

1990-08-02

NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ] CLOSED [ ] ORIGINATOR CONTROL NUMBER: SSDD-0002 PROGRAM OFFICE CONTROL NUMBER: DATA ITEM DISCREPANCY WORKSHEET CDRL NUMBER: A002-06 DATE: 08/02/90 ORIGINATOR NAME: John J. Brassil OFFICE SYMBOL: SAIC TELEPHONE NUMBER: 272-2999 SUBSTANTIVE: X EDITORIAL: PAGE NUMBER: 35 PARA NUMBER: 4.2.1.3.1 COMMENT OR RECOMMENDED CHANGE: Add subordinate paragraphs to describe the 3-digit System Capabilities that are listed under System Administration in Appendix G. RATIONALE: Both Process Outbound Cargo

KBSA Project Management Assistant. Volume 1.

DTIC Science & Technology

1987-07-01

perforrim automiated syitim,’i. of j)r)gIiIIm, fm r specified 󈧏,,al-. ti ,. forth. The rationale for and benefits deriving foint tt,- 1. l* ’m m , arc...efficiently, as well as its interface to human user,. It is therefore of priun iiiict an,’," " to employ a language that allows the formalization of...km wledge th It i convenienT . I ;ITw the conceptual level of humans and efficiently manipulable by the PM A.. ’ In order to achieve these somewhat

How might acupuncture work? A systematic review of physiologic rationales from clinical trials.

PubMed

Moffet, Howard H

2006-07-07

Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. The author conducted a PubMed search to obtain a fair sample of acupuncture clinical trials published in English in 2005. Each article was reviewed for a physiologic rationale, as well as study objectives and outcomes, experimental and control interventions, country of origin, funding sources and journal type. Seventy-nine acupuncture clinical trials were identified. Twenty-six studies (33%) offered no physiologic rationale. Fifty-three studies (67%) posited a physiologic basis for acupuncture: 33 (62% of 53) proposed neurochemical mechanisms, 2 (4%) segmental nervous system effects, 6 (11%) autonomic nervous system regulation, 3 (6%) local effects, 5 (9%) effects on brain function and 5 (9%) other effects. No rationale was proposed for stroke; otherwise having a rationale was not associated with objective, positive or negative findings, means of intervention, country of origin, funding source or journal type. The dominant explanation for how acupuncture might work involves neurochemical responses and is not reported to be dependent on treatment objective, specific points, means or method of stimulation. Many acupuncture trials fail to offer a meaningful rationale, but proposing a rationale can help investigators to develop and test a causal hypothesis, choose an appropriate control and rule out placebo effects. Acupuncture may stimulate self-regulatory processes independent of the treatment objective, points, means or methods used; this would account for acupuncture's reported benefits in so many disparate pathologic conditions.

Assessing the Rationales for Educational Reforms: A Test of the Professional Development, Comprehensive Reform, and Direct Instruction Hypotheses. Policy Research Report.

ERIC Educational Resources Information Center

St. John, Edward P.; Manset, Genevieve; Chung, Choong-Geun; Worthington, Kimberly

Educational reforms are advocated based on rationales that emerge from the research literature. However, evaluation studies seldom examine whether the rationales used to argue for a reform actually hold up when empirical evidence is examined after the reform has been implemented. This paper examines survey data from 3 years of analyses of early…

Treating alcoholism through a narrative approach. Case study and rationale.

PubMed Central

Kaminsky, D.; Rabinowitz, S.; Kasan, R.

1996-01-01

A case study illustrates the narrative or story-telling approach to treating alcoholism. We discuss the rationale for this method and describe how it could be useful in family practice for treating people with alcohol problems. PMID:8653035

Supplement use in sport: is there a potentially dangerous incongruence between rationale and practice?

PubMed Central

Petróczi, Andrea; Naughton, Declan P

2007-01-01

Background Supplement use by athletes is complex and research supports the alarming notion of misinformed decisions regarding supplements. Hypothesis A frequent divergence between the type of supplements chosen by athletes and the rationale dictating the supplement use is hypothesized. Thus, a potentially dangerous incongruence may exist between rationale and practice. Testing the hypothesis In the continued absence of reliable data on supplement use, an alternative approach of studying the reasons underlying supplement use in athletes is proposed to determine whether there is an incongruence between rationale and practice. Existing data from large scale national surveys can be used to investigate this incongruence. Implications of the hypothesis In this report, analyses of distinctive patterns between the use and rationale for use of supplements among athletes are recommended to explore this potentially dangerous phenomenon. PMID:17535442

STARPROBE: Scientific rationale

NASA Technical Reports Server (NTRS)

Underwood, J. H. (Editor); Randolph, J. E. (Editor)

1982-01-01

The scientific rationale and instrumentation problems in the areas of solar internal dynamics and relativity, solar plasma and particle dynamics, and solar atmosphere structure were studied. Current STARPROBE mission and system design concepts are summarized.

Information Management of a Structured Admissions Interview Process in a Medical College with an Apple II System

PubMed Central

O'Reilly, Robert; Fedorko, Steve; Nicholson, Nigel

1983-01-01

This paper describes a structured interview process for medical school admissions supported by an Apple II computer system which provides feedback to interviewers and the College admissions committee. Presented are the rationale for the system, the preliminary results of analysis of some of the interview data, and a brief description of the computer program and output. The present data show that the structured interview yields very high interrater reliability coefficients, is acceptable to the medical school faculty, and results in quantitative data useful in the admission process. The system continues in development at this time, a second year of data will be shortly available, and further refinements are being made to the computer program to enhance its utilization and exportability.

Is fibular fracture displacement consistent with tibiotalar displacement?

PubMed

van den Bekerom, Michel P J; van Dijk, C Niek

2010-04-01

We believed open reduction with internal fixation is required for supination-external rotation ankle fractures located at the level of the distal tibiofibular syndesmosis (Lauge-Hanssen SER II and Weber B) with 2 mm or more fibular fracture displacement. The rationale for surgery for these ankle fractures is based on the notion of elevated intraarticular contact pressures with lateral displacement. To diagnose these injuries, we presumed that in patients with a fibular fracture with at least 2 mm fracture displacement, the lateral malleolus and talus have moved at least 2 mm in a lateral direction without medial displacement of the proximal fibula. We reviewed 55 adult patients treated operatively for a supination-external rotation II ankle fracture (2 mm or more fibular fracture displacement) between 1990 and 1998. On standard radiographs, distance from the tibia to the proximal fibula, distance from the tibia to the distal fibula, and displacement at the level of the fibular fracture were measured. These distances were compared preoperatively and postoperatively. We concluded tibiotalar displacement cannot be reliably assessed at the level of the fracture. Based on this and other studies, we believe there is little evidence to perform open reduction and internal fixation of supination-external rotation II ankle fractures. Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

PreSSUB II: The prehospital stroke study at the Universitair Ziekenhuis Brussel II

PubMed Central

Espinoza, Alexis Valenzuela; Van Hooff, Robbert-Jan; De Smedt, Ann; Moens, Maarten; Yperzeele, Laetitia; Nieboer, Koenraad; Hubloue, Ives; De Keyser, Jacques; Dupont, Alain; De Wit, Liesbet; Putman, Koen; Brouns, Raf

2015-01-01

Rationale Stroke is a time-critical medical emergency requiring specialized treatment. Prehospital delay contributes significantly to delayed or missed treatment opportunities. In-ambulance telemedicine can bring stroke expertise to the prehospital arena and facilitate this complex diagnostic and therapeutic process. Aims This study evaluates the efficacy, safety, feasibility, reliability and cost-effectiveness of in-ambulance telemedicine for patients with suspicion of acute stroke. We hypothesize that this approach will reduce the delay to in-hospital treatment by streamlining the diagnostic process and that prehospital stroke care will be improved by expert stroke support via telemedicine during the ambulance transportation. Design PreSSUB II is an interventional, prospective, randomized, open-blinded, end-point, single-center trial comparing standard emergency care by the Paramedic Intervention Team of the Universitair Ziekenhuis Brussel (control) with standard emergency care complemented with in-ambulance teleconsultation service by stroke experts (PreSSUB). Study Outcomes The primary efficacy endpoint is the call-to-brain imaging time. Secondary endpoints for the efficacy analysis include the prevalence of medical events diagnosed and corrected during in-ambulance teleconsultation, the proportion of patients with ischemic stroke receiving recanalization therapy, the assessment of disability, functional status, quality of life and overall well-being. Mortality at 90 days after stroke is the primary safety endpoint. Secondary safety analysis will involve the registration of any adverse event. Other analyses include assessment of feasibility and reliability and a health economic evaluation. PMID:27847888

A beginner's guide to writing the nursing conceptual model-based theoretical rationale.

PubMed

Gigliotti, Eileen; Manister, Nancy N

2012-10-01

Writing the theoretical rationale for a study can be a daunting prospect for novice researchers. Nursing's conceptual models provide excellent frameworks for placement of study variables, but moving from the very abstract concepts of the nursing model to the less abstract concepts of the study variables is difficult. Similar to the five-paragraph essay used by writing teachers to assist beginning writers to construct a logical thesis, the authors of this column present guidelines that beginners can follow to construct their theoretical rationale. This guide can be used with any nursing conceptual model but Neuman's model was chosen here as the exemplar.

Crystallographic snapshots of active site metal shift in E. coli fructose 1,6-bisphosphate aldolase.

PubMed

Tran, Huyen-Thi; Lee, Seon-Hwa; Ho, Thien-Hoang; Hong, Seung-Hye; Huynh, Kim-Hung; Ahn, Yeh-Jin; Oh, Deok-Kun; Kang, Lin-Woo

2016-12-01

Fructose 1,6-bisphosphate aldolase (FBA) is important for both glycolysis and gluconeogenesis in life. Class II (zinc dependent) FBA is an attractive target for the development of antibiotics against protozoa, bacteria, and fungi, and is also widely used to produce various high-value stereoisomers in the chemical and pharmaceutical industry. In this study, the crystal structures of class II Escherichia coli FBA (EcFBA) were determined from four different crystals, with resolutions between 1.8 Å and 2.0 Å. Native EcFBA structures showed two separate sites of Zn1 (interior position) and Zn2 (active site surface position) for Zn2＋ ion. Citrate and TRIS bound EcFBA structures showed Zn2＋ position exclusively at Zn2. Crystallographic snapshots of EcFBA structures with and without ligand binding proposed the rationale of metal shift at the active site, which might be a hidden mechanism to keep the trace metal cofactor Zn2＋ within EcFBA without losing it. [BMB Reports 2016; 49(12): 681-686].

Child Development and Social Studies Curriculum Design: Toward a Rationale.

ERIC Educational Resources Information Center

Knox, Gary A.

This paper is a working draft of a study which has examined the accumulated research on child growth and development. The draft is designed as an input paper to enable the Marin Social Studies Project to refine its rationale and criteria for a recommended K-12 social studies program of curriculum options. Identification of the capabilities of…

Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

ERIC Educational Resources Information Center

Friedmann, Peter D.; Katz, Elizabeth C.; Rhodes, Anne G.; Taxman, Faye S.; O'Connell, Daniel J.; Frisman, Linda K.; Burdon, William M.; Fletcher, Bennett W.; Litt, Mark D.; Clarke, Jennifer; Martin, Steven S.

2008-01-01

This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment…

Including the Study about Religions in the Social Studies Curriculum: A Position Statement and Guidelines.

ERIC Educational Resources Information Center

Dilzer, Robert J., Jr.

Based on a National Council for the Social Studies position statement on the essentials of social studies, a rationale for teaching about religions in the social studies is presented. The author's rationale includes the following points: (1) that knowledge about religion is not only characteristic of an educated person but also necessary for…

Recommended System Design for the Occupational Health Management Information System (OHMIS). Volume 1.

DTIC Science & Technology

1983-04-01

Management Information System (OHMIS). The system design includes: detailed function data flows for each of the core data processing functions of OHMIS, in the form of input/processing/output algorithms; detailed descriptions of the inputs and outputs; performance specifications of OHMIS; resources required to develop and operate OHMIS (Vol II). In addition, the report provides a summary of the rationale used to develop the recommended system design, a description of the methodology used to develop the recommended system design, and a review of existing

Measuring Student Performance: Assessment in the Social Studies. Theme Issue.

ERIC Educational Resources Information Center

Kiernan, Henry, Ed.; Pyne, John, Ed.

1993-01-01

The four articles in this theme issue provide an overview of assessment in the social studies and the rationale behind the movement for a more authentic assessment of learning outcomes. In the first article, "Thinking as an Unnatural Act," William T. Daly offers a clear rationale for social studies teachers to re-examine the methods of assessing…

Kin-selected cooperation without lifetime monogamy: human insights and animal implications.

PubMed

Kramer, Karen L; Russell, Andrew F

2014-11-01

Recent phylogenetic analyses suggest that monogamy precedes the evolution of cooperative breeding involving non-breeding helpers. The rationale: only through monogamy can helper-recipient relatedness coefficients match those of parent-offspring. Given that humans are cooperative breeders, these studies imply a monogamy bottleneck during hominin evolution. However, evidence from multiple sources is not compelling. In reconciliation, we propose that selection against cooperative breeding under alternative mating patterns will be mitigated by: (i) kin discrimination, (ii) reduced birth-intervals, and (iii) constraints on independent breeding, particularly for premature and post-fertile individuals. We suggest that such alternatives require consideration to derive a complete picture of the selection pressures acting on the evolution of cooperative breeding in humans and other animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.

PubMed

Konopleva, Marina; Pollyea, Daniel A; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L; Blum, William; DiNardo, Courtney D; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2016-10-01

We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. Cancer Discov; 6(10); 1106-17. ©2016 AACRSee related commentary by Pullarkat and Newman, p. 1082This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

PubMed

Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

2014-04-01

Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values <10 g/dL without an increase of ≥ 0.5 g/dL). The background, rationale and study design of the trial are presented here. The study has been completed and results are expected in late 2013. FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

Early markers of airways inflammation and occupational asthma: Rationale, study design and follow-up rates among bakery, pastry and hairdressing apprentices

PubMed Central

Tossa, Paul; Bohadana, Abraham; Demange, Valérie; Wild, Pascal; Michaely, Jean-Pierre; Hannhart, Bernard; Paris, Christophe; Zmirou-Navier, Denis

2009-01-01

Background Occupational asthma is a common type of asthma caused by a specific agent in the workplace. The basic alteration of occupational asthma is airways inflammation. Although most patients with occupational asthma are mature adults, there is evidence that airways inflammation starts soon after inception of exposure, including during apprenticeship. Airways hyper responsiveness to methacholine is a valid surrogate marker of airways inflammation, which has proved useful in occupational epidemiology. But it is time-consuming, requires active subject's cooperation and is not readily feasible. Other non-invasive and potentially more useful tests include the forced oscillation technique, measurement of fraction exhaled nitric oxide, and eosinophils count in nasal lavage fluid. Methods and design This study aims to investigate early development of airways inflammation and asthma-like symptoms in apprentice bakers, pastry-makers and hairdressers, three populations at risk of occupational asthma whose work-related exposures involve agents of different nature. The objectives are to (i) examine the performance of the non-invasive tests cited above in detecting early airways inflammation that might eventually develop into occupational asthma; and (ii) evaluate whether, and how, constitutional (e.g. atopy) and behavioural (e.g. smoking) risk factors for occupational asthma modulate the effects of allergenic and/or irritative substances involved in these occupations. This paper presents the study rationale and detailed protocol. Discussion Among 441 volunteers included at the first visit, 354 attended the fourth one. Drop outs were investigated and showed unrelated to the study outcome. Sample size and follow-up participation rates suggest that the data collected in this study will allow it to meet its objectives. PMID:19389222

Early markers of airways inflammation and occupational asthma: rationale, study design and follow-up rates among bakery, pastry and hairdressing apprentices.

PubMed

Tossa, Paul; Bohadana, Abraham; Demange, Valérie; Wild, Pascal; Michaely, Jean-Pierre; Hannhart, Bernard; Paris, Christophe; Zmirou-Navier, Denis

2009-04-23

Occupational asthma is a common type of asthma caused by a specific agent in the workplace. The basic alteration of occupational asthma is airways inflammation. Although most patients with occupational asthma are mature adults, there is evidence that airways inflammation starts soon after inception of exposure, including during apprenticeship. Airways hyper responsiveness to methacholine is a valid surrogate marker of airways inflammation, which has proved useful in occupational epidemiology. But it is time-consuming, requires active subject's cooperation and is not readily feasible. Other non-invasive and potentially more useful tests include the forced oscillation technique, measurement of fraction exhaled nitric oxide, and eosinophils count in nasal lavage fluid. This study aims to investigate early development of airways inflammation and asthma-like symptoms in apprentice bakers, pastry-makers and hairdressers, three populations at risk of occupational asthma whose work-related exposures involve agents of different nature. The objectives are to (i) examine the performance of the non-invasive tests cited above in detecting early airways inflammation that might eventually develop into occupational asthma; and (ii) evaluate whether, and how, constitutional (e.g. atopy) and behavioural (e.g. smoking) risk factors for occupational asthma modulate the effects of allergenic and/or irritative substances involved in these occupations. This paper presents the study rationale and detailed protocol. Among 441 volunteers included at the first visit, 354 attended the fourth one. Drop outs were investigated and showed unrelated to the study outcome. Sample size and follow-up participation rates suggest that the data collected in this study will allow it to meet its objectives.

Education about Aging: A Rationale.

ERIC Educational Resources Information Center

Wass, Hannelore; And Others

1981-01-01

Reviews studies on children's and adolescents' attitudes about aging. Analyzes media content such as children's literature, textbooks, and public television programs to determine how older persons are portrayed. Provides a rationale for systematic education about aging in the public schools. (Author)

Young adults' responses to alternative messages describing a sugar-sweetened beverage price increase.

PubMed

Gollust, Sarah E; Tang, Xuyang; White, James M; French, Simone A; Runge, Carlisle Ford; Rothman, Alexander J

2017-01-01

Many jurisdictions in the USA and globally are considering raising the prices of sugar-sweetened beverages (SSB) through taxes as a strategy to reduce their consumption. The objective of the present study was to identify whether the rationale provided for an SSB price increase affects young adults' behavioural intentions and attitudes towards SSB. Participants were randomly assigned to receive one of eight SSB price increase rationales. Intentions to purchase SSB and attitudes about the product and policy were measured. A forty-six-item cross-sectional Internet survey. Undergraduate students (n 494) at a large US Midwestern university. Rationale type was significantly associated with differences in participants' purchasing intentions for the full sample (F 7,485=2·53, P=0·014). Presenting the rationale for an SSB price increase as a user fee, an effort to reduce obesity, a strategy to offset health-care costs or to protect children led to lower SSB purchasing intentions compared with a message with no rationale. Rationale type was also significantly associated with differences in perceptions of soda companies (F 7,485=2·10, P=0·043); among low consumers of SSB, messages describing the price increase as a user fee or tax led to more negative perceptions of soda companies. The rationale attached to an SSB price increase could influence consumers. However, these message effects may depend on individuals' level of SSB consumption.

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

Impacts of Outer Continental Shelf (OCS) development on recreation and tourism. Volume 3. Detailed methodology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The final report for the project is presented in five volumes. This volume, Detailed Methodology Review, presents a discussion of the methods considered and used to estimate the impacts of Outer Continental Shelf (OCS) oil and gas development on coastal recreation in California. The purpose is to provide the Minerals Management Service with data and methods to improve their ability to analyze the socio-economic impacts of OCS development. Chapter II provides a review of previous attempts to evaluate the effects of OCS development and of oil spills on coastal recreation. The review also discusses the strengths and weaknesses of differentmore » approaches and presents the rationale for the methodology selection made. Chapter III presents a detailed discussion of the methods actually used in the study. The volume contains the bibliography for the entire study.« less

The Association of Daily Physical Symptoms with Future Health

PubMed Central

Leger, Kate A.; Charles, Susan T.; Ayanian, John Z.; Almeida, David M.

2015-01-01

Rationale Daily physical symptoms play a critical role in health and illness experiences. Despite their daily prevalence, the ability of these symptoms to predict future health status is debated. Objective The current study examined whether physical symptom reports predict future health outcomes independent of trait measures of emotion. Methods Participants (N = 1189) who completed both Midlife in the United States (MIDUS) Surveys I and II as well as the National Study of Daily Experiences (NSDE) reported their daily physical symptoms at baseline and number of reported chronic conditions and functional disability nearly 10 years later. Results Physical symptoms at baseline significantly predicted the occurrence of chronic conditions and functional impairment at long-term follow-up, even after adjusting for self-reported affect, self-reported health, and previous health status. Conclusion Findings suggest that daily physical symptoms are unique indicators of future health status. PMID:26364011

A technology program for the development of the large deployable reflector for space based astronomy

NASA Technical Reports Server (NTRS)

Kiya, M. K.; Gilbreath, W. P.; Swanson, P. N.

1982-01-01

Technologies for the development of the Large Deployable Reflector (LDR), a NASA project for the 1990's, for infrared and submillimeter astronomy are presented. The proposed LDR is a 10-30 diameter spaceborne observatory operating in the spectral region from 30 microns to one millimeter, where ground observations are nearly impossible. Scientific rationales for such a system include the study of ancient signals from galaxies at the edge of the universe, the study of star formation, and the observation of fluctuations in the cosmic background radiation. System requirements include the ability to observe faint objects at large distances and to map molecular clouds and H II regions. From these requirements, mass, photon noise, and tolerance budgets are developed. A strawman concept is established, and some alternate concepts are considered, but research is still necessary in the areas of segment, optical control, and instrument technologies.

Mother-child conversations about safety: implications for socializing safety values in children.

PubMed

O'Neal, Elizabeth E; Plumert, Jodie M

2014-05-01

This study examined how mothers socialize their children about safety through conversations about potentially unsafe activities. Mothers and their 8- and 10-year-old children discussed and rated the safety of 12 photographs depicting another same-gender child engaged in potentially dangerous activities. Conversations usually unfolded with children giving the first rating or rationale, followed by additional discussion between the mother and child. Mothers and children relied on 2 main types of rationales to justify their ratings: potential outcomes of the activity and specific features of the situation (dangerous and nondangerous). Mothers (but not children) used dangerous feature rationales more often than dangerous outcome rationales. When disagreements arose, mothers typically guided children to adopt their own rating rather than the child's rating. Additionally, children who used more nondangerous feature and outcome rationales had experienced more injuries requiring medical attention. Mothers' focus on dangerous features appears to reflect their efforts to help children make causal connections between dangerous elements of the situation and adverse outcomes that might result.

Rationale, study design, and implementation of the ACS1 study: effect of azilsartan on circadian and sleep blood pressure as compared with amlodipine.

PubMed

Kario, Kazuomi; Hoshide, Satoshi

2014-06-01

The ACS1 (Azilsartan Circadian and Sleep Pressure - the first study) is a multicenter, randomized, open-label, two parallel-group study carried out to investigate the efficacy of an 8-week oral treatment with azilsartan 20 mg in comparison with amlodipine 5 mg. The patients with stage I or II primary hypertension will be randomly assigned to either an azilsartan group (n=350) or an amlodipine group (n=350). The primary endpoint is a change in nocturnal systolic blood pressure (BP) as measured by ambulatory BP monitoring at the end of follow-up relative to the baseline level during the run-in period. In addition, we will carry out the same analysis after dividing four different nocturnal BP dipping statuses (extreme-dippers, dippers, nondipper, and risers). The findings of this study will help in establishing an appropriate antihypertensive treatment for hypertensive patients with a disrupted circadian BP rhythm.

Rationale, study design, and implementation of the ACS1 study: effect of azilsartan on circadian and sleep blood pressure as compared with amlodipine

PubMed Central

Hoshide, Satoshi

2014-01-01

Objective The ACS1 (Azilsartan Circadian and Sleep Pressure – the first study) is a multicenter, randomized, open-label, two parallel-group study carried out to investigate the efficacy of an 8-week oral treatment with azilsartan 20 mg in comparison with amlodipine 5 mg. Materials and methods The patients with stage I or II primary hypertension will be randomly assigned to either an azilsartan group (n=350) or an amlodipine group (n=350). The primary endpoint is a change in nocturnal systolic blood pressure (BP) as measured by ambulatory BP monitoring at the end of follow-up relative to the baseline level during the run-in period. In addition, we will carry out the same analysis after dividing four different nocturnal BP dipping statuses (extreme-dippers, dippers, nondipper, and risers). Conclusion The findings of this study will help in establishing an appropriate antihypertensive treatment for hypertensive patients with a disrupted circadian BP rhythm. PMID:24637789

Prospector II: Towards a knowledge base for mineral deposits

USGS Publications Warehouse

McCammon, R.B.

1994-01-01

What began in the mid-seventies as a research effort in designing an expert system to aid geologists in exploring for hidden mineral deposits has in the late eighties become a full-sized knowledge-based system to aid geologists in conducting regional mineral resource assessments. Prospector II, the successor to Prospector, is interactive-graphics oriented, flexible in its representation of mineral deposit models, and suited to regional mineral resource assessment. In Prospector II, the geologist enters the findings for an area, selects the deposit models or examples of mineral deposits for consideration, and the program compares the findings with the models or the examples selected, noting the similarities, differences, and missing information. The models or the examples selected are ranked according to scores that are based on the comparisons with the findings. Findings can be reassessed and the process repeated if necessary. The results provide the geologist with a rationale for identifying those mineral deposit types that the geology of an area permits. In future, Prospector II can assist in the creation of new models used in regional mineral resource assessment and in striving toward an ultimate classification of mineral deposits. ?? 1994 International Association for Mathematical Geology.

Meeting a Moral Imperative: A Rationale for Teaching the Holocaust

ERIC Educational Resources Information Center

Lindquist, David H.

2011-01-01

A primary rationale for studying the Holocaust (Shoah) involves the opportunity to consider the moral implications that can be drawn from examining the event. Studying the Shoah forces students to consider what it means to be human and humane by examining the full continuum of individual behavior, from "ultimate evil" to "ultimate good". This…

Postoperative surgical complications of lymphadenohysterocolpectomy

PubMed Central

Marin, F; Pleşca, M; Bordea, CI; Voinea, SC; Burlănescu, I; Ichim, E; Jianu, CG; Nicolăescu, RR; Teodosie, MP; Maher, K; Blidaru, A

2014-01-01

Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. Methods and results Patients were divided according to the type of surgery performed as follows: for cervical cancer – group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer. Abbreviations: PRS- Piver Rutledge-Smith, II- class II, III- class III PMID:24653760

Evidence-informed recommendations for constructing and disseminating messages supplementing the new Canadian Physical Activity Guidelines

PubMed Central

2013-01-01

Background Few validated guidelines exist for developing messages in health promotion practice. In clinical practice, the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) Instrument is the international gold standard for guideline assessment, development, and reporting. In a case study format, this paper describes the application of the AGREE II principles to guide the development of health promotion guidelines for constructing messages to supplement the new Canadian Physical Activity Guidelines (CPAG) released in 2011. Methods The AGREE II items were modified to suit the objectives of developing messages that (1) clarify key components of the new CPAG and (2) motivate Canadians to meet the CPAG. The adapted AGREE II Instrument was used as a systematic guide for the recommendation development process. Over a two-day meeting, five workgroups (one for each CPAG – child, youth, adult, older adult – and one overarching group) of five to six experts (including behavior change, messaging, and exercise physiology researchers, key stakeholders, and end users) reviewed and discussed evidence for creating and targeting messages to supplement the new CPAG. Recommendations were summarized and reviewed by workgroup experts. The recommendations were pilot tested among end users and then finalized by the workgroup. Results The AGREE II was a useful tool in guiding the development of evidence-based specific recommendations for constructing and disseminating messages that supplement and increase awareness of the new CPAG (child, youth, adults, and older adults). The process also led to the development of sample messages and provision of a rationale alongside the recommendations. Conclusions To our knowledge, these are the first set of evidence-informed recommendations for constructing and disseminating messages supplementing physical activity guidelines. This project also represents the first application of international standards for guideline development (i.e., AGREE II) to the creation of practical recommendations specifically aimed to inform health promotion and public health practice. The messaging recommendations have the potential to increase the public health impact of evidence-based guidelines. PMID:23634998

Inquiry into terminal decline: five objectives for future study.

PubMed

Gerstorf, Denis; Ram, Nilam

2013-10-01

Notions of terminal decline propose that late-life change is primarily driven by processes closely tied to pathology and mortality rather than chronological age. We use the rationales of longitudinal research as outlined by Baltes and Nesselroade (Baltes, P., & Nesselroade, J. [1979]. History and rationale of longitudinal research. In J. R. Nesselroade & P. Baltes (Eds.), Longitudinal research in the study of behavior and development [pp. 1-39]. San Diego, CA: Academic Press) as a framework for organizing research on terminal decline. In doing so, we note that there are relatively robust descriptions of terminal decline across a variety of different domains, as well as the extent of interindividual differences in the levels of function, rates of change, and timing of terminal decline (research rationales 1 and 2). However, there is much more to learn about the interrelations among change in different domains, the underlying mechanisms of change, and the factors that contribute to interindividual differences in change (research rationales 3-5). Needed are new study designs and analytical models that better address the structural, temporal, and causal interrelations that contribute to and protect against terminal decline.

Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma.

PubMed

Dankner, Matthew; Lajoie, Mathieu; Moldoveanu, Dan; Nguyen, Tan-Trieu; Savage, Paul; Rajkumar, Shivshankari; Huang, Xiu; Lvova, Maria; Protopopov, Alexei; Vuzman, Dana; Hogg, David; Park, Morag; Guiot, Marie-Christine; Petrecca, Kevin; Mihalcioiu, Catalin; Watson, Ian R; Siegel, Peter M; Rose, April A N

2018-06-14

Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX). We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these to wild-type or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, LY3009120), MEKi (cobimetinib, trametinib, binimetinib) or the combination. We identified two patients with BRAF L597S metastatic melanoma who were treated with dMAPKi. BRAFi impaired MAPK signalling and cell growth in class I and II BRAF mutant cells. dMAPKi was more effective than either single MAPKi at inhibiting cell growth in all class II BRAF mutant cells tested. dMAPKi caused tumor regression in two melanoma PDXs with class II BRAF mutations, and prolonged survival of mice with class II BRAF mutant melanoma brain metastases. Two patients with BRAF L597S mutant melanoma clinically responded to dMAPKi. Class II BRAF mutant melanoma are growth inhibited by dMAPKi. Responses to dMAPKi have been observed in two patients with class II BRAF mutant melanoma. This data provides rationale for clinical investigation of dMAPKi in patients with class II BRAF mutant metastatic melanoma. Copyright ©2018, American Association for Cancer Research.

Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

PubMed

Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

2015-04-01

The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Women's Perspectives of Personal Trainers: A Qualitative Study.

PubMed

Melton, Deana; Dail, Teresa K; Katula, Jeffrey A; Mustian, Karen M

2011-01-01

Personal trainers play an integral role in the day-to-day operation of the facilities in which they work. Research has identified a number of qualities and competencies necessary to be an effective exercise leader, but there is little scholarly work addressing clients' attitudes related to the performance of personal trainers. Utilizing focus group methodology, female clients of personal trainers were recruited to provide viewpoints related to the desirable qualities of personal trainers, as well as opinions regarding trainer certification and academic preparation. Responses of the participants were transcribed, coded, and analyzed for themes. Four global themes emerged: Selection Rationale, Personal Trainer Rationale, Loyalty Rationale and Negative Characteristics. Selection Rationale consisted of qualities that influence a client's decision to hire a particular trainer (e.g., physique, results observed in other clients, social skills). Personal Trainer Rationale referred to the clients' reasons (e.g., frustration with current fitness level) for hiring a specific trainer. Loyalty Rationale referred to the credentials of a personal trainer that solidify the client/trainer relationship and Negative Characteristics referred to qualities considered unethical or unprofessional. The results suggest that undergraduate exercise science programs should devote additional time toward the development of future fitness trainers' affective qualities and that clients' would benefit from information about the credentials of personal trainers.

Women's Perspectives of Personal Trainers: A Qualitative Study

PubMed Central

Melton, Deana; Dail, Teresa K.; Katula, Jeffrey A.; Mustian, Karen M.

2015-01-01

Personal trainers play an integral role in the day-to-day operation of the facilities in which they work. Research has identified a number of qualities and competencies necessary to be an effective exercise leader, but there is little scholarly work addressing clients' attitudes related to the performance of personal trainers. Utilizing focus group methodology, female clients of personal trainers were recruited to provide viewpoints related to the desirable qualities of personal trainers, as well as opinions regarding trainer certification and academic preparation. Responses of the participants were transcribed, coded, and analyzed for themes. Four global themes emerged: Selection Rationale, Personal Trainer Rationale, Loyalty Rationale and Negative Characteristics. Selection Rationale consisted of qualities that influence a client's decision to hire a particular trainer (e.g., physique, results observed in other clients, social skills). Personal Trainer Rationale referred to the clients' reasons (e.g., frustration with current fitness level) for hiring a specific trainer. Loyalty Rationale referred to the credentials of a personal trainer that solidify the client/trainer relationship and Negative Characteristics referred to qualities considered unethical or unprofessional. The results suggest that undergraduate exercise science programs should devote additional time toward the development of future fitness trainers' affective qualities and that clients' would benefit from information about the credentials of personal trainers. PMID:26005398

Neuromodulation for cephalgias

PubMed Central

Rasskazoff, Serge Y.; Slavin, Konstantin V.

2013-01-01

Headaches (cephalgias) are a common reason for patients to seek medical care. There are groups of patients with recurrent headache and craniofacial pain presenting with malignant course of their disease that becomes refractory to pharmacotherapy and other medical management options. Neuromodulation can be a viable treatment modality for at least some of these patients. We review the available evidence related to the use of neuromodulation modalities for the treatment of medically refractory craniofacial pain of different nosology based on the International Classification of Headache Disorders, 2nd edition (ICHD-II) classification. This article also reviews the scientific rationale of neuromodulation application in management of cephalgias. PMID:23682340

Cargo Movement Operations System (CMOS) Interface Requirements Specification (Draft). Increment II

DTIC Science & Technology

1990-05-17

NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ 3 CLOSED [ ] ORIGINATOR CONTROL NUMBER: IRS1-0003 PROGRAM OFFICE CONTROL NUMBER: DATA ITEM DISCREPANCY WORKSHEET CDRL NUMBER: A004-05 DATE: 05/17/90 ORIGINATOR NAME: Ronald J. Lacour OFFICE SYMBOL: SAIC TELEPHONE NUMBER: 272-2999 SUBSTANTIVE: X EDITORIAL: PAGE NUMBER: 9 PARA NUMBER: 3.2 c. COMMENT OR RECOMMENDED CHANGE: Change line 2 to read, "CMOS IRD/SBSS-01 and SBSS-03." Move "CMOS IRD/SBSS-02" to paragraph 3.3 c. RATIONALE: The CMOS IRD/SBSS-02 covers the Shipment Suspense

Cargo Movement Operations System (CMOS). Final Software Design Document for the Applications CSCI, Increment II

DTIC Science & Technology

1991-10-03

NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ CLOSED [] ORIGINATOR CONTROL NUMBER: SDDl-0002 PROGRAM OFFiCE CONTROL NUMBER: DATA ITEM DISCREPANCY WORKSHEET CDRL NUMBER: A006-0250L DATE: 10/03/11 ORIGINATOR NAME: Ronald J. Lacour OFFICE SYMBOL: SAIC TELEPHONE NUMBER: 272-2999 SUBSTANTIVE: X EDITORIAL: PAGE NUMBER: CU2A5040-19 PARA NUMBER: N/A COMMENT OR RECOMMENDED CHANGE: Add "STANDBY PAX" on the last page of this screen. RATIONALE: This redesigned page is for handling standby passengers. However, no mention of that is present.

A modified tensionless gingival grafting technique using acellular dermal matrix.

PubMed

Taylor, John B; Gerlach, Robert C; Herold, Robert W; Bisch, Frederick C; Dixon, Douglas R

2010-10-01

Conventional surgical procedures designed for autogenous tissue material may not be appropriate when using acellular dermal matrix (ADM) for the treatment of gingival recessions. This article describes a new surgical technique that addresses the unique and sensitive aspects of ADM specifically to improve esthetic outcomes and gain increased clinical predictability when treating Miller Class I and II gingival recession defects. In this paper, a root coverage case is described and the specific steps and rationale for this new technique are explained. This technique has been predictable clinically, with results comparable to those achieved using autogenous tissue.

Effects of an International Experience Requirement, Year in School, and Preferred Program Duration on Student Interest in Study Abroad

ERIC Educational Resources Information Center

Richart, Adrienne F.

2015-01-01

Several compelling rationales have driven dramatic increases in the number of students that U.S. American postsecondary institutions send abroad each year. The rationales are political, academic, cultural/social, and economic in nature and undeniably integral to developing graduates who are prepared to compete in the global arena. This study was…

Training for Corrections: Rationale and Techniques.

ERIC Educational Resources Information Center

Southern Illinois Univ., Carbondale. Center for the Study of Crime, Delinquency and Corrections.

A manual focuses on how to teach in inservice training programs for professional personnel in correctional agencies. A chapter on rationale discusses training objectives and curriculum. A second chapter covers learning environment, lesson plans, and learning problems. One, on teaching techniques, covers lecture, group discussion, case study,…

An International Assessment of Bachelor Degree Graduates' Learning Outcomes

ERIC Educational Resources Information Center

Coates, Hamish; Richardson, Sarah

2012-01-01

This paper examines rationales, aspirations, assumptions and methods shaping an international assessment of learning outcomes: the OECD's Assessment of Higher Education Learning Outcomes (AHELO) feasibility study. The first part of the paper is analytical, exploring formative rationales, and shaping contexts and normative perspectives that frame…

Long-term use and tolerability of irbesartan for control of hypertension

PubMed Central

Forni, Valentina; Wuerzner, Grégoire; Pruijm, Menno; Burnier, Michel

2011-01-01

In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150–300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics. PMID:21949635

Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions.

PubMed

Spring, Laura; Bardia, Aditya; Modi, Shanu

2016-01-01

Dysregulation of the cyclin D-cyclin-dependent kinase (CDK) 4/6-INK4-retinoblastoma (Rb) pathway is an important contributor to endocrine therapy resistance. Recent clinical development of selective inhibitors of CDK4 and CDK6 kinases has led to renewed interest in cell cycle regulators, following experience with relatively non-selective pan-CDK inhibitors that often resulted in limited activity and poor safety profiles in the clinic. The highly selective oral CDK 4/6 inhibitors palbociclib (PD0332991), ribociclib (LEE011), and abemaciclib (LY2835219) are able to inhibit the proliferation of Rb-positive tumor cells and have demonstrated dose-dependent growth inhibition in ER+ breast cancer models. In metastatic breast cancer, all three agents are being explored in combination with endocrine therapy in Phase III studies. Results so far indicated promising efficacy and manageable safety profiles, and led to the FDA approval of palbociclib. Phase II-III studies of these agents, in combination with endocrine therapy, are also underway in early breast cancer in the neoadjuvant and adjuvant settings. Selective CDK 4/6 inhibitors are also being investigated with other targeted agents or chemotherapy in the advanced setting. This article reviews the rationale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer. Future trials evaluating further combination strategies with CDK 4/6 backbone and translational studies refining predictive biomarkers are needed to help personalize the optimal treatment regimen for individual patients with ER+ breast cancer.

Structure-activity relationships of sialogogic heptapeptides analogous to physalaemin.

PubMed

Gao, C; Abe, K

2000-05-01

The rationale behind this study was to determine in detail which amino acids in physalaemin are crucial to its sialogogue activity, with a view of synthesizing new sialogogues which might be of use in the treatment of dry mouth. With the progressive elimination of amino acids, one by one, from the C- and N-terminal regions, 126 heptapeptides were newly synthesized by the multipin peptide method, for comparison with II naturally occurring tachykinins. The C-terminal amide in position II was essential for salivation, but not the pyrolidine group or the N-terminal amino acid residues in positions I to 4. In 18 heptapeptides in which M in position II (MII) was replaced by another amino acid, one by one, none caused salivation. In 18 heptapeptides, in which L10 or G9 was replaced, three peptides caused salivation but none had significantly increased secretory activities. In 18 heptapeptides in which Y8 was replaced, four caused salivation but only one (I) had significantly increased secretory activity. In 18 heptapeptides in which F7 was replaced, only Y caused salivation but with significantly reduced secretory activity. In contrast, in 18 heptapeptides in which K6 and N5 were replaced, most caused salivation and some of them had significantly increased secretory activities. It is concluded that the sequence FYGLM-NH2 conserved in the C-terminal region of physalaemin is optimal, that amides in position II and F7 are very important for salivation, but that K6 and N5 can be replaced by some other amino acids, resulting in increased secretory activities.

Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan.

PubMed

Chrysant, Steven G

2017-07-01

LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF. The synergism from these drugs arises from the vasodilating effects of valsartan through its blockade of Ang II type 1 receptor and the action of natriuretic peptides atrial natriuretic peptide and B-type natriuretic peptide (BNP) by preventing their catabolism with neprilysin resulting in increase of cyclic guanosine monophosphate. This action of neprilysin is associated with increased natriuresis, diuresis, and systemic vasodilation, since these peptides have been shown to have potent diuretic, natriuretic, and vasodilating effects. In addition, it reduces the levels of N terminal pro-BNP. Therefore, administration of LCZ-696 results in significant reduction of wall stress from pressure and volume overload of the left ventricle as demonstrated by the reduction of N terminal pro-BNP, both significant constituents of hypertension and HF, and it is safe, well tolerated and is almost free of cough and angioedema. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

On the Interplay Between Adhesion Strength and Tensile Properties of Thermal Spray Coated Laminates—Part II: Low-Velocity Thermal Spray Coatings

NASA Astrophysics Data System (ADS)

Luo, Xiaotao; Smith, Gregory M.; Sampath, Sanjay

2018-02-01

In this two-part study, uniaxial tensile testing was used to evaluate coating/substrate bonding and compared with traditional ASTM C633 bond pull test results for thermal spray (TS) coated steel laminates. In Part I, the rationale, methodology, and applicability of the test to high-velocity TS coatings were demonstrated. In this Part II, the method was investigated for low-velocity TS processes (air plasma spray and arc spray) on equivalent materials. Ni and Ni-5wt.%Al coatings were deposited on steel substrates with three different roughness levels and tested using both uniaxial tensile and ASTM C633 methods. The results indicate the uniaxial tensile approach provides useful information about the nature of the coating/substrate bonding and goes beyond the traditional bond pull test in providing insightful information on the load sharing processes across the interface. Additionally, this proposed methodology alleviates some of the longstanding shortcomings and potentially reduces error associated with the traditional ASTM C633 test. The mechanisms governing the load transfer between the substrate and the coating were investigated, and the influence of Al in the coating material evaluated.

An Educator's Guide to the Literature Dealing with the Rationale for Steroid Use, Effects They Have on Body Composition and Performance, with Solutions to Preventing Steroid Abuse in Youth.

ERIC Educational Resources Information Center

Dawson, Tim R.

This study provides information about steroids and recommends programs to educators and coaches who are involved with educating students about steroid abuse. The first part of the study contains annotations that examine the rationale and motivation of those who have used anabolic steroids. The next part of the study contains annotations that…

The Impact of a Course on Nature of Science Pedagogical Views and Rationales. Comparing Preservice Teachers in Their First Versus Second Experience

NASA Astrophysics Data System (ADS)

Kruse, Jerrid W.; Easter, Jaclyn M.; Edgerly, Hallie S.; Seebach, Colin; Patel, Neal

2017-08-01

This study explored changes in preservice teachers' (PSTs) nature of science pedagogical (NOSP) views and nature of science (NOS) rationales using pre- and post-course written responses as well as interview data. Through systematic analysis, themes were generated and compared to the NOS literature. Comparisons between pre- and post-course data demonstrate improved and deepened NOS views, NOSP views that are more aligned with NOS literature, and a greater number of rationales for including NOS. All participants were enrolled in the "Inquiry and Natures of Science, Technology, and Engineering" (INSTE) course. However, six participants were enrolled in INSTE as their first course in which NOS and NOSP were addressed. The other six participants were enrolled in INSTE as their second course in which NOS and NOSP were addressed, with science methods as their first course in which NOS and NOSP were addressed. By comparing participants enrolled in INSTE as their first course to those enrolled in INSTE as their second course, we observed that NOS understanding seemed to develop in a first experience alongside some NOS rationales, but NOSP views lagged for participants in INSTE as their first course. Participants enrolled in INSTE as their second course developed more robust and literature-aligned NOSP views and more multifaceted NOS rationales. Therefore, this study bolsters arguments that teachers need to receive extended NOS and NOSP instruction.

Public financing of IVF: a review of policy rationales.

PubMed

Mladovsky, Philipa; Sorenson, Corinna

2010-06-01

There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed.

l-Citrulline Protects from Kidney Damage in Type 1 Diabetic Mice

PubMed Central

Romero, Maritza J.; Yao, Lin; Sridhar, Supriya; Bhatta, Anil; Dou, Huijuan; Ramesh, Ganesan; Brands, Michael W.; Pollock, David M.; Caldwell, Ruth B.; Cederbaum, Stephen D.; Head, C. Alvin; Bagi, Zsolt; Lucas, Rudolf; Caldwell, Robert W.

2013-01-01

Rationale: Diabetic nephropathy (DN) is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of l-arginine (l-arg), the substrate for endothelial nitric oxide synthase (eNOS), failed to improve vascular function. l-Citrulline (l-cit) supplementation not only increases l-arg synthesis, but also inhibits cytosolic arginase I, a competitor of eNOS for the use of l-arg, in the vasculature. Aims: To investigate whether l-cit treatment reduces DN in streptozotocin (STZ)-induced type 1 diabetes (T1D) in mice and rats and to study its effects on arginase II (ArgII) function, the main renal isoform. Methods: STZ-C57BL6 mice received l-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and l-cit-treated STZ-rats were evaluated. Results: l-Citrulline exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis, and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, l-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 weeks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater blood urea nitrogen levels, hypertrophy, and dilated tubules than diabetic wild type (WT) mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic WT animals. l-Cit also restored nitric oxide/reactive oxygen species balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, l-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1β and IL-12(p70) generation in the human proximal tubular cells. Conclusion: l-Citrulline supplementation established an anti-inflammatory profile and significantly preserved the nephron function during T1D. PMID:24400007

New in silico insights into the inhibition of RNAP II by α-amanitin and the protective effect mediated by effective antidotes.

PubMed

Garcia, Juliana; Carvalho, Alexandra T P; Dourado, Daniel F A R; Baptista, Paula; de Lourdes Bastos, Maria; Carvalho, Félix

2014-06-01

Poisonous α-amanitin-containing mushrooms are responsible for the major cases of fatalities after mushroom ingestion. α-Amanitin is known to inhibit the RNA polymerase II (RNAP II), although the underlying mechanisms are not fully understood. Benzylpenicillin, ceftazidime and silybin have been the most frequently used drugs in the management of α-amanitin poisoning, mostly based on empirical rationale. The present study provides an in silico insight into the inhibition of RNAP II by α-amanitin and also on the interaction of the antidotes on the active site of this enzyme. Docking and molecular dynamics (MD) simulations combined with molecular mechanics-generalized Born surface area method (MM-GBSA) were carried out to investigate the binding of α-amanitin and three antidotes benzylpenicillin, ceftazidime and silybin to RNAP II. Our results reveal that α-amanitin should affects RNAP II transcription by compromising trigger loop (TL) function. The observed direct interactions between α-amanitin and TL residues Leu1081, Asn1082, Thr1083, His1085 and Gly1088 alters the elongation process and thus contribute to the inhibition of RNAP II. We also present evidences that α-amanitin can interact directly with the bridge helix residues Gly819, Gly820 and Glu822, and indirectly with His816 and Phe815. This destabilizes the bridge helix, possibly causing RNAP II activity loss. We demonstrate that benzylpenicillin, ceftazidime and silybin are able to bind to the same site as α-amanitin, although not replicating the unique α-amanitin binding mode. They establish considerably less intermolecular interactions and the ones existing are essential confine to the bridge helix and adjacent residues. Therefore, the therapeutic effect of these antidotes does not seem to be directly related with binding to RNAP II. RNAP II α-amanitin binding site can be divided into specific zones with different properties providing a reliable platform for the structure-based drug design of novel antidotes for α-amatoxin poisoning. An ideal drug candidate should be a competitive RNAP II binder that interacts with Arg726, Ile756, Ala759, Gln760 and Gln767, but not with TL and bridge helix residues. Copyright © 2014 Elsevier Inc. All rights reserved.

The Rhetoric of Issue Advertising: A Rationale, a Case Study, a Critical Perspective--And More.

ERIC Educational Resources Information Center

Heath, Robert L.

1988-01-01

Supports the use of issue advertising. Argues that speech communication scholars can facilitate the responsible and effective use of issue ads. Reviews critics and proponents of issue advertising. Develops a rationale to guide the practice of issue advertising. Examines issue advertising in the current pro-nuclear campaign. (MS)

The Importance of Rationales for Internationalization at a Local Level--University and Individual

ERIC Educational Resources Information Center

Willis, Ian; Taylor, John

2014-01-01

This study examines rationales for internationalization at a research intensive university in the UK. Internationalization is often described at a macro level without reaching down to explore the individual motivations that may support or constrain internationalization at a particular institution. The article argues that it is important to…

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

ESSAYS, ANALYSIS, AND--BETTER WRITING.

ERIC Educational Resources Information Center

STEWART, DONALD C.

A STUDY OF THE NATURE AND UTILITY OF TYPES OF ESSAY ANTHOLOGIES DESIGNED FOR FRESHMAN COMPOSITION COURSES WAS CONDUCTED IN ORDER TO DETERMINE (1) WHAT ARE THE RATIONALES, ORGANIZATION, CONTENT, AND INSTRUCTIONAL APPARATUS OF THE MOST WIDELY ADOPTED READERS, (2) HAVE THE RATIONALES FOR THEIR USE VARIED SINCE SUCH TEXTS APPEARED, AND (3) IS THE…

Teacher Grading Decisions: Influences, Rationale, and Practices

ERIC Educational Resources Information Center

Kunnath, Joshua P.

2017-01-01

This mixed-methods study applied a decision-making theoretical framework to an investigation of teacher grading in a large urban school district in California. A sample of 251 high school teachers of core subjects were surveyed, and 15 teachers participated in four focus group interviews in order provide data on the influences, rationale, and…

Enhancing Life Satisfaction by Government Accountability in China

ERIC Educational Resources Information Center

Cheung, Chau-kiu; Leung, Kwan-kwok

2007-01-01

Finding the rationale for democracy requires not merely a conceptual task but also an empirical study. One rationale is that democracy maximizes people's happiness by satisfying everyone. A further qualification of this is that democracy minimizes the maximum regret of the disadvantaged. This is compatible with the protection theory of government,…

A Psychological Rationale for Adventure Therapy with Hospitalized Adolescents.

ERIC Educational Resources Information Center

Gillis, H. L.; And Others

The purpose of this study was to examine the Wechsler Intelligence Scale for Children-Revised (WISC-R) profiles of two treatment populations and present a theoretical rationale for using adventure therapy. Data for the first group were obtained from the psychological testing records of 150 randomly selected inpatients (81 males, 69 females)…

Throwing Caution to the Wind: Rationales for Risky Behavior.

ERIC Educational Resources Information Center

de La Rue, Denise; Ruback, R. Barry

There appears to be a tendency for people who have not been victimized by negative life events to perceive themselves as less vulnerable to victimization than others. Research has revealed this unrealistic optimism in risk perception. A study on rationales for risky behaviors was conducted to identify reasons other than this illusion of…

A Rationale for Mixed Methods (Integrative) Research Programmes in Education

ERIC Educational Resources Information Center

Niaz, Mansoor

2008-01-01

Recent research shows that research programmes (quantitative, qualitative and mixed) in education are not displaced (as suggested by Kuhn) but rather lead to integration. The objective of this study is to present a rationale for mixed methods (integrative) research programs based on contemporary philosophy of science (Lakatos, Giere, Cartwright,…

Critical Pedagogy(ies) for ELT in Indonesia

ERIC Educational Resources Information Center

Larson, Kasey R.

2014-01-01

This paper will explore the theoretical underpinnings that present a rationale for the use of critical pedagogy as an English Language Teaching (ELT) approach in Indonesia. A brief description of critical pedagogy is given, followed by a detailed rationale for its use including an overview of critical pedagogy studies done in Asia, an exploration…

What Is Implementation Research? Rationale, Concepts, and Practices

ERIC Educational Resources Information Center

Bhattacharyya, Onil; Reeves, Scott; Zwarenstein, Merrick

2009-01-01

Despite the growing knowledge base on evidence-based practices in social work and medicine, there is a large gap between what is known and what is consistently done. Implementation research is the study of methods to promote the uptake of research findings into routine practice. In this article, we describe the rationale for implementation…

Navy Shipbuilding: Need to Document Rationale for the Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added Incentives

DTIC Science & Technology

2017-03-01

NAVY SHIPBUILDING Need to Document Rationale for the Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added...Use of Fixed-Price Incentive Contracts and Study Effectiveness of Added Incentives What GAO Found Over 80 percent of the Navy’s shipbuilding...mackinm@gao.gov. Why GAO Did This Study DOD encourages the use of FPI contracts because they allow for equitable sharing of costs savings and risk

Rationales for Commonly "Challenged" Taught Books.

ERIC Educational Resources Information Center

Shugert, Diane P., Ed.; And Others

1983-01-01

Intended for teachers, this focused journal issue contains separate rationales for teaching books that have been challenged as appropriate instructional materials. Following a discussion of the purpose for rationales and suggestions for using them, the journal presents rationales for teaching the following books: "To Kill a Mockingbird,""The Diary…

Involving citizens in priority setting for public health research: Implementation in infection research.

PubMed

Rawson, Timothy M; Castro-Sánchez, Enrique; Charani, Esmita; Husson, Fran; Moore, Luke S P; Holmes, Alison H; Ahmad, Raheelah

2018-02-01

Public sources fund the majority of UK infection research, but citizens currently have no formal role in resource allocation. To explore the feasibility and willingness of citizens to engage in strategic decision making, we developed and tested a practical tool to capture public priorities for research. A scenario including six infection themes for funding was developed to assess citizen priorities for research funding. This was tested over two days at a university public festival. Votes were cast anonymously along with rationale for selection. The scenario was then implemented during a three-hour focus group exploring views on engagement in strategic decisions and in-depth evaluation of the tool. 188/491(38%) prioritized funding research into drug-resistant infections followed by emerging infections(18%). Results were similar between both days. Focus groups contained a total of 20 citizens with an equal gender split, range of ethnicities and ages ranging from 18 to >70 years. The tool was perceived as clear with participants able to make informed comparisons. Rationale for funding choices provided by voters and focus group participants are grouped into three major themes: (i) Information processing; (ii) Knowledge of the problem; (iii) Responsibility; and a unique theme within the focus groups (iv) The potential role of citizens in decision making. Divergent perceptions of relevance and confidence of "non-experts" as decision makers were expressed. Voting scenarios can be used to collect, en-masse, citizens' choices and rationale for research priorities. Ensuring adequate levels of citizen information and confidence is important to allow deployment in other formats. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Rationale for hedging initiatives: Empirical evidence from the energy industry

NASA Astrophysics Data System (ADS)

Dhanarajata, Srirajata

Theory offers different rationales for hedging including (i) financial distress and bankruptcy cost, (ii) capacity to capture attractive investment opportunities, (iii) information asymmetry, (iv) economy of scale, (v) substitution for hedging, (vi) managerial risk aversion, and (vii) convexity of tax schedule. The purpose of this dissertation is to empirically test the explanatory power of the first five theoretical rationales on hedging done by oil and gas exploration and production (E&P) companies. The level of hedging is measured by the percentage of production effectively hedged, calculated based on the concept of delta and delta-gamma hedging. I employ Tobit regression, principal components, and panel data analysis on dependent and raw independent variables. Tobit regression is applied due to the fact that the dependent variable used in the analysis is non-negative. Principal component analysis helps to reduce the dimension of explanatory variables while panel data analysis combines/pools the data that is a combination of time-series and cross-sectional. Based on the empirical results, leverage level is consistently found to be a significant factor on hedging activities, either due to an attempt to avoid financial distress by the firm, or an attempt to control agency cost by debtholders, or both. The effect of capital expenditures and discretionary cash flows are both indeterminable due possibly to a potential mismatch in timing of realized cash flow items and hedging decision. Firm size is found to be positively related to hedging supporting economy of scale hypothesis, which is introduced in past literature, as well as the argument that large firm usually are more sophisticated and should be more willing and more comfortable to use hedge instruments than smaller firms.

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

Identification and Structural Basis of Binding to Host Lung Glycogen by Streptococcal Virulence Factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lammerts van Bueren,A.; Higgins, M.; Wang, D.

2007-01-01

The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basismore » for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal {alpha}-glucan-metabolizing machinery as virulence factors.« less

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors

NASA Astrophysics Data System (ADS)

Rubin, Joshua B.; Kung, Andrew L.; Klein, Robyn S.; Chan, Jennifer A.; Sun, Yanping; Schmidt, Karl; Kieran, Mark W.; Luster, Andrew D.; Segal, Rosalind A.

2003-11-01

The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Gi protein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.

Qualitative research methods in renal medicine: an introduction.

PubMed

Bristowe, Katherine; Selman, Lucy; Murtagh, Fliss E M

2015-09-01

Qualitative methodologies are becoming increasingly widely used in health research. However, within some specialties, including renal medicine, qualitative approaches remain under-represented in the high-impact factor journals. Qualitative research can be undertaken: (i) as a stand-alone research method, addressing specific research questions; (ii) as part of a mixed methods approach alongside quantitative approaches or (iii) embedded in clinical trials, or during the development of complex interventions. The aim of this paper is to introduce qualitative research, including the rationale for choosing qualitative approaches, and guidance for ensuring quality when undertaking and reporting qualitative research. In addition, we introduce types of qualitative data (observation, interviews and focus groups) as well as some of the most commonly encountered methodological approaches (case studies, ethnography, phenomenology, grounded theory, thematic analysis, framework analysis and content analysis). © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Rationale for Students' Participation in University Governance and Organizational Effectiveness in Ekiti and Ondo States, Nigeria

ERIC Educational Resources Information Center

Akomolafe, C. O.; Ibijola, E. Y.

2012-01-01

The study investigated the rationale for students' participation in university governance and organizational effectiveness. A descriptive research of survey design was adopted. The population consisted of all staff and students of Ekiti State University, Ado Ekiti, Ekiti State and Adekunle Ajasin University, Akungba-Akoko, Ondo State. 700 subjects…

Four Rationales of HE Internationalization: Perspectives of U.K. Universities on Attracting Students from Former Soviet Countries

ERIC Educational Resources Information Center

Chankseliani, Maia

2018-01-01

In the context marked by increasing competition between nation-states and universities, expanding individualization, growing influence of nonstate actors, and the new reality of Brexit, this study uses narrative and numeric data to explore the rationales of U.K. higher education (HE) internationalization, specifically motives of attracting…

Mobility as a Continuum: European Commission Mobility Policies for Schools and Higher Education

ERIC Educational Resources Information Center

Dvir, Yuval; Yemini, Miri

2017-01-01

This study explores the rationale and aims of European Commission (EC) mobility programmes for schools and higher education systems, namely the Comenius and the European Action Scheme for the Mobility of University Students (ERASMUS) funding schemes. Our findings indicate that the aims, rationales and means of mobility programmes for the school…

Teaching Economics to Young Adolescents: A Research-Based Rationale.

ERIC Educational Resources Information Center

Davis, James E.

This booklet presents a research-based rationale for teaching economics at the middle/junior high school level in the United States. Chapter 1, "Introduction," describes the project in which the rationale was developed and outlines the remainder of the document. Chapter 2, "Elements of a Rationale for Middle School Economic Education," presents…

No-migration variance petition. Appendices A--B: Volume 2, Revision 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-03-01

Volume II contains Appendix A, emergency plan and Appendix B, waste analysis plan. The Waste Isolation Pilot Plant (WIPP) Emergency plan and Procedures (WP 12-9, Rev. 5, 1989) provides an organized plan of action for dealing with emergencies at the WIPP. A contingency plan is included which is in compliance with 40 CFR Part 265, Subpart D. The waste analysis plan provides a description of the chemical and physical characteristics of the wastes to be emplaced in the WIPP underground facility. A detailed discussion of the WIPP Waste Acceptance Criteria and the rationale for its established units are also included.

United States Foreign Policy RE: The Third World - The Economic Dimension.

DTIC Science & Technology

1985-05-06

system is strong and resilient.඙ Although as a banker one might assume these reasons rather parochial he caveats his rationale with the statement that...8217. - (~~~~ ~~ 0.-1 9,,("C CQi C~a ~ lvt. Vlce Piorc ted t nea earcc~ ’es and 12 )’ g u zira rI~ ,E) InJ.a S 0p Y N td e (p ii1 3 APPENDIX 1V JNVFS~hNT r~C~’LPWfIC...Central African Empire NMauritius Zambia Chad Nexico Zimbabwe Chile N.Ongol ia Colombia Norocco Comoro Islands Nozambique Conga Nepal Costa Rica

The credibility of exposure therapy: Does the theoretical rationale matter?

PubMed

Arch, Joanna J; Twohig, Michael P; Deacon, Brett J; Landy, Lauren N; Bluett, Ellen J

2015-09-01

Little is understood about how the public perceives exposure-based therapy (ET) for treating anxiety and trauma-related disorders or how ET rationales affect treatment credibility. Distinct approaches to framing ET are practiced, including those emphasized in traditional cognitive behavioral therapy, acceptance and commitment therapy, and the more recent inhibitory learning model. However, their relative effect on ET's credibility remains unknown. A final sample of 964 U.S. adults provided baseline views of ET. Participants rated ET treatment credibility following a simple ET definition (pre-rationale) and following randomization to rationale modules addressing ET goals, fear, and cognitive strategies from distinct theoretical perspectives (post-rationale). Baseline ET views, symptoms, and sociodemographic characteristics were examined as putative moderators and predictors. At baseline, the majority had never heard of ET. From pre- to post-rationale, ET treatment credibility significantly increased but the rationales' theoretical perspective had little impact. More negative baseline ET views, specific ethnic/racial minority group status, and lower education moderated or predicted greater increases in treatment credibility following the rationale. ET remains relatively unknown as a treatment for anxiety or trauma, supporting the need for direct-to-consumer marketing. Diverse theory-driven rationales similarly increased ET credibility, particularly among those less likely to use ET. Copyright © 2015 Elsevier Ltd. All rights reserved.

HPTN 071 (PopART): rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial.

PubMed

Hayes, Richard; Ayles, Helen; Beyers, Nulda; Sabapathy, Kalpana; Floyd, Sian; Shanaube, Kwame; Bock, Peter; Griffith, Sam; Moore, Ayana; Watson-Jones, Deborah; Fraser, Christophe; Vermund, Sten H; Fidler, Sarah

2014-02-13

Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. ClinicalTrials.gov NCT01900977.

[Alpha-melanocyte-stimulating hormone. From bench to bedside].

PubMed

Böhm, M; Luger, T A

2010-06-01

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that is produced by the skin itself from the precursor proopiomelanocortin. It crucially mediates ultraviolet light-induced tanning after binding to melanocortin-1 receptors (MC-1R) expressed on the surface of epidermal melanocytes. The potent pigment-inducing and also cytoprotective actions of alpha-MSH are the rationale for the performance of first phase II clinical trials with Nle4-D-Phe7-alpha-MSH (NDP-alpha-MSH), a subcutaneously administered synthetic and superpotent alpha-MSH analogue, in patients with photodermatoses such as erythropoietic protoporphyria. Since alpha-MSH has shown promising anti-inflammatory and antifibrotic properties in numerous preclinical studies, it will be most interesting to evaluate these effects in further clinical pilot studies with NDP-alpha-MSH. In addition to alpha-MSH analogues, truncated tripeptides such as KDPT which do not bind to MC-1R but have sustained anti-inflammatory properties are currently emerging as another novel therapeutic strategy in dermatology.

Why Do Higher Education Institutions Internationalize? An Investigation of the Multilevel Determinants of Internationalization Rationales

ERIC Educational Resources Information Center

Seeber, Marco; Cattaneo, Mattia; Huisman, Jeroen; Paleari, Stefano

2016-01-01

In recent decades internationalization has risen to prominence in higher education institutions (HEIs). Scholars have identified several rationales for internationalization. There is however a lack of conceptual understanding and empirical evidence for which rationale(s) for internationalization are chosen by a given HEI and why. The goal of this…

Neuronal ceroid lipofuscinosis type CLN2: A new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America

PubMed Central

Kohan, Romina; Noelia Carabelos, María; Xin, Winnie; Sims, Katherine; Guelbert, Norberto; Adriana Cismondi, Inés; Pons, Patricia; Alonso, Graciela Irene; Troncoso, Mónica; Witting, Scarlet; Pearce, David A.; de Kremer, Raquel Dodelson; Oller-Ramírez, Ana María; de Halac, Inés Noher

2013-01-01

Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n=11, null TPP1 activity in leukocytes; (II) n=8, residual TPP1 activity of 0.60–15.85 nmol/h/mg (nr 110–476); (III) n=6, activity not measured in leukocytes. Curvilinear bodies (CB) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887-10A>G (intron 7), and to a lesser extent at c.89+5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at nonconserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity. PMID:23266810

Cognitive Defusion versus Thought Distraction: A Clinical Rationale, Training, and Experiential Exercise in Altering Psychological Impacts of Negative Self-Referential Thoughts

ERIC Educational Resources Information Center

Masuda, Akihiko; Feinstein, Amanda B.; Wendell, Johanna W.; Sheehan, Shawn T.

2010-01-01

Using two modes of intervention delivery, the present study compared the effects of a cognitive defusion strategy with a thought distraction strategy on the emotional discomfort and believability of negative self-referential thoughts. One mode of intervention delivery consisted of a clinical rationale and training (i.e., Partial condition). The…

Rationales of a Shift towards Knowledge Economy in Jordan from the Viewpoint of Educational Experts and Relationship with Some Variables

ERIC Educational Resources Information Center

Al Zboon, Mohammad Saleem; Al Ahmad, Suliman Diab Ali; Al Zboon, Saleem Odeh

2009-01-01

The purpose of the present study was to identify rationales underlying a shift towards knowledge economy in education as perceived by the educational experts in Jordan and relationship with some variables. The random stratum sample (n = 90) consisted of educational experts representing faculty members in the Jordanian universities and top leaders…

Access and Success for African American Engineers and Computer Scientists: A Case Study of Two Predominantly White Public Research Universities

ERIC Educational Resources Information Center

Newman, Christopher Bufford

2011-01-01

Over the past decade, three rationales have emerged for emphasizing the reinforcement of the United States' science, technology, engineering, and mathematics (STEM) pipeline. The first rationale pertains to U.S. global competitiveness, the second revolves around the benefits of a diverse workforce, and the third argument points to social justice…

Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic responses, and experiences.

PubMed

Accardi, Michelle; Cleere, Colleen; Lynn, Steven Jay; Kirsch, Irving

2013-10-01

In this study participants were provided with either the standard rationale that accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne, 1962) or a rationale that presented hypnosis as a nondeceptive placebo, consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The effects of the placebo and standard rationales were highly comparable with respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective, and involuntariness measures of hypnotic responding; as well as a variety of subjective experiences during hypnosis, as measured by the Phenomenology of Consciousness Inventory (Pekala, 1982). Differences among correlations were not evident when measures were compared across groups. However, indices of hypnotic responding were correlated with attitudes in the hypnosis but not the placebo condition, and, generally speaking, the link between subjective experiences during hypnosis and measures of hypnotic responding were more reliable in the placebo than the hypnosis group. Researcher findings are neutral with respect to providing support for altered state versus sociocognitive models of hypnosis.

Client cognitive responses to counselor paradoxical and nonparadoxical directives.

PubMed

Lee, D Y; Rossiter, B; Martin, J; Uhlemann, M R

1990-09-01

Client cognitive responses to counselor paradoxical and nonparadoxical directives were examined. It was predicted (a) that clients who received paradoxical symptom prescriptions would display a greater negativity toward the counselor and counseling than those who received nonparadoxical directives; and (b) that clients who received no rationale for the paradoxical directives would display a greater negativity than those who received a rationale. Thirty clients who had reported performance anxiety received one 45-minute counseling interview. Ten clients received paradoxical directives with a rationale, 10 received paradoxical directives with no rationale, and 10 received nonparadoxical directives. Results showed no significant differences in either client in-session negativity or out-of-session implementation of directives between the paradoxical and nonparadoxical conditions and between the rationale and no rationale paradoxical conditions. Possible implications of the findings are discussed.

The potential of SGLT2 inhibitors in phase II clinical development for treating type 2 diabetes.

PubMed

Pafili, K; Maltezos, E; Papanas, N

2016-10-01

There is now an abundance of anti-diabetic agents. However, only few patients achieve glycemic targets. Moreover, current glucose-lowering agents mainly depend upon insulin secretion or function. Sodium glucose co-transporter type 2 (SGLT2) inhibitors present a novel glucose-lowering therapy, inducing glycosuria in an insulin-independent fashion. In this review, the authors discuss the key efficacy and safety data from phase II clinical trials in type 2 diabetes mellitus (T2DM) of the main SGLT2 inhibitors approved or currently in development, and provide a rationale for their use in T2DM. Despite the very promising characteristics of this new therapeutic class, a number of issues await consideration. One important question is what to expect from head-to-head comparison data. We also need to know if dual inhibition of SGLT1/SGLT2 is more efficacious in reducing HbA1c and how this therapy affects metabolic and cardiovascular parameters. Additionally, several SGLT2 agents that have not yet come to market have hitherto been evaluated in Asian populations, whereas approved SGLT2 inhibitors have been frequently studied in other populations, including Caucasian subjects. Thus, we need more information on the potential role of ethnicity on their efficacy and safety.

Parents' and children's knowledge of oral health: a qualitative study of children with cleft palate.

PubMed

Davies, Karen; Lin, Yin-Ling; Callery, Peter

2017-07-01

Children with cleft lip and/or palate (CLP) are prone to poorer oral health outcomes than their peers, with serious implications for treatment. Little is known of the knowledge and practice of children with CLP in caring for teeth and how these contribute to oral health. To investigate (i) parents' and children's knowledge of oral health, (ii) how knowledge is acquired, and (iii) how knowledge is implemented. A qualitative design was used to investigate knowledge, beliefs, and practices reported by parents and children, age 5-11 years with CLP. Data were collected from 22 parents and 16 children and analysed using thematic analysis. Four themes were derived as follows: (i) implicit knowledge: children express simple knowledge underpinned by basic rationales, (ii) situated knowledge: children gain skills as part of everyday childhood routines, (iii) maintaining good practice in oral health: parents take a lead role in motivating, monitoring, and maintaining children's toothbrushing, and (iv) learning opportunities: pivotal moments provide opportunities for children to extend their knowledge. Developers of oral health education interventions should take account of children's implicit knowledge and the transmission of beliefs between generations that influence toothbrushing behaviours. This could enhance interventions to support parents and children's practice. © 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Promoting older peoples' participation in activity, whose responsibility? A case study of the response of health, local government and voluntary organizations.

PubMed

Goodman, C; Davies, S; Tai, S See; Dinan, S; Iliffe, S

2007-10-01

The benefits for older people of participating in regular activity are well documented. This paper focuses on how publicly funded community-based organizations enable older people to engage in physical activity. The research questions were: (i) What activity promotion schemes/initiatives exist for older people? (ii) Who has responsibility for them, how are they funded and organized and what evidence exists of interagency working? (iii) Who are the older people that participate? (iv) What are the perceived and measurable outcomes of the initiatives identified? To establish the type and range of provision for older people in a sector of London, the strategies and information about existing activity promoting schemes of inner city health, local government and voluntary organizations were reviewed. Key informants were then interviewed to establish the rationale, achievements and different schemes. One hundred and nine activity-promoting initiatives for older people were identified. Most were provided within an environment of short-term funding and organizational upheaval and reflected eclectic theoretical and ideological approaches. The findings demonstrate: (i) the need for organizations to apply evidence about what attracts and sustains older people's participation in physical activity, and (ii) the need to develop funded programmes that build on past achievements, have explicit outcomes and exploit opportunities for cross agency working.

Phase I trial of a yeast-based therapeutic cancer vaccine (GI-6301) targeting the transcription factor brachyury

PubMed Central

Heery, Christopher R.; Singh, B. Harpreet; Rauckhorst, Myrna; Marté, Jennifer L.; Donahue, Renee N.; Grenga, Italia; Rodell, Timothy C.; Dahut, William; Arlen, Philip M.; Madan, Ravi A.; Schlom, Jeffrey; Gulley, James L.

2015-01-01

The nuclear transcription factor brachyury has previously been shown to be a strong mediator of the epithelial-to-mesenchymal transition (EMT) in human carcinoma cells and a strong negative prognostic factor in several tumor types. Brachyury is overexpressed in a range of human carcinoma as well as in chordoma, a rare tumor for which there is no standard systemic therapy. Preclinical studies have shown a recombinant Saccharomyces cerevisiae (yeast) vaccine encoding brachyury (GI-6301) can activate human T cells in vitro. A Phase I dose escalation (3+3 design) trial enrolled 34 patients at 4 dose levels (3, 3, 16, and 11 patients, respectively, at 4, 16, 40, and 80 yeast units (YU)). Expansion cohorts were enrolled at 40 and 80 YU dose levels for analysis of immune response and clinical activity. We observed brachyury-specific T-cell immune responses in the majority of evaluable patients despite most having been heavily pretreated. No evidence of autoimmunity or other serious adverse events were observed. Two chordoma patients showed evidence of disease control (one mixed response and one partial response). A patient with colorectal carcinoma, who enrolled on study with a large progressing pelvic mass and rising CEA, remains on study for greater than 1 year with stable disease, evidence of decreased tumor density and decreased serum CEA. This study is the first-in-human to demonstrate the safety and immunogenicity of this therapeutic cancer vaccine and provides rationale for exploration in Phase II studies. A randomized Phase II chordoma study is enrolling. PMID:26130065

Large Deployable Reflector (LDR) feasibility study update

NASA Technical Reports Server (NTRS)

Alff, W. H.; Banderman, L. W.

1983-01-01

In 1982 a workshop was held to refine the science rationale for large deployable reflectors (LDR) and develop technology requirements that support the science rationale. At the end of the workshop, a set of LDR consensus systems requirements was established. The subject study was undertaken to update the initial LDR study using the new systems requirements. The study included mirror materials selection and configuration, thermal analysis, structural concept definition and analysis, dynamic control analysis and recommendations for further study. The primary emphasis was on the dynamic controls requirements and the sophistication of the controls system needed to meet LDR performance goals.

GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates

PubMed Central

Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

2017-01-01

Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design. PMID:28467806

GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

PubMed

Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

2017-06-13

Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data.

PubMed

Kassem, Loay; Abdel-Rahman, Omar

2016-12-01

mTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers. A comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results. A total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed. mTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Secondary School Students Learning from Reflections on the Rationale behind Self-Made Errors: A Field Experiment

ERIC Educational Resources Information Center

Heemsoth, Tim; Heinze, Aiso

2016-01-01

Thus far, it is unclear how students can learn most effectively from their own errors. In this study, reflections on the rationale behind self-made errors are assumed to enhance knowledge acquisition. In a field experiment with pre/post/follow-up design, the authors practiced fractions with 174 seventh- and eighth-grade students who were randomly…

Evaluating the Rationale for Affirmative Action in College Admissions: Direct and Indirect Relationships between Campus Diversity and Gains in Understanding Diverse Groups

ERIC Educational Resources Information Center

Pike, Gary R.; Kuh, George D.; Gonyea, Robert M.

2007-01-01

Affirmative action in college admissions is based on the premise that a diverse student body contributes to interactions among students from different backgrounds, which are in turn positively related to desirable outcomes of college. This study evaluates the merits of this rationale for affirmative action by examining the direct and indirect…

The Examination of Secondary Education Chemistry Curricula Published between 1957-2007 in Terms of the Dimensions of Rationale, Goals, and Subject-Matter

ERIC Educational Resources Information Center

Pekdag, Bulent; Erol, Hilal

2013-01-01

Fifteen secondary education chemistry curricula published from 1957 until 2007 were examined based on the dimensions of rationale, goals, and subject matter. An examination of documents in the scope of qualitative research was carried out in the study. The goals included in the examined chemistry curricula were analyzed according to the cognitive,…

The Impact of a Course on Nature of Science Pedagogical Views and Rationales: Comparing Preservice Teachers in Their First versus Second Experience

ERIC Educational Resources Information Center

Kruse, Jerrid W.; Easter, Jaclyn M.; Edgerly, Hallie S.; Seebach, Colin; Patel, Neal

2017-01-01

This study explored changes in preservice teachers' (PSTs) nature of science pedagogical (NOSP) views and nature of science (NOS) rationales using pre- and post-course written responses as well as interview data. Through systematic analysis, themes were generated and compared to the NOS literature. Comparisons between pre- and post-course data…

An Examination on the Chinese Students' Rationales to Receive Their Higher Education in the U.S.

ERIC Educational Resources Information Center

Chao, Chiang-Nan

2017-01-01

This research attempts to explore the rationales why so many Chinese students choose to study abroad and why the United States is their preferred destination. This population is small, but a vital component of university life at many colleges and a much needed source of financial revenue. A total of 380 students completed a questionnaire yielding…

Antimicrobial stewardship: a qualitative study of the development of national guidelines for antibiotic use in hospitals.

PubMed

Feiring, Eli; Walter, Anne Berit

2017-11-21

As effective antibiotics are becoming a scarce resource, governmental regulation is needed to promote responsible use. Implementation of antibiotic stewardship and practice guidelines in health care facilities seems to be crucial to this effort. Empirical studies suggest, however, that guidelines have limited influence on health professionals' behavior and practice. Barriers and facilitators to guideline implementability are much studied, but little attention has been given to health professionals' perceptions of normative acceptability of guidelines as a condition for compliance. The aim of the present study was first, to examine if and how aspects potentially promoting acceptability and compliance among clinical target users were addressed during development of Norwegian national guidelines for antibiotic use in hospitals and second, to identify procedural characteristics of the development process that were perceived by target users to yield legitimate guidelines. Qualitative deductive thematic analysis was used. A theoretical framework inspired by the AGREE II Instrument and the Accountability for reasonableness framework assisted data gathering and interpretation. Archival data was collected and used to detail the guideline development process. Semi-structured, in-depth interviews with eight clinicians with extensive knowledge of the guidelines were carried out. Guideline development was characterized by i) broad agreement about scope and purpose, ii) broad involvement of stakeholders in the development process, iii) use of systematic methods to search for and apply evidence, iv) easily identifiable and specific recommendations, v) provision of tools on how to put recommendations into practice, and vi) editorial independence. Several procedural characteristics were perceived by the interviewees as promoting guideline legitimacy; i) diverse perspectives systematically involved in the process, ii) accessibility and transparency of the rationales for decision making, iii) opportunities for appeals and reconsiderations, and iv) regulative authority. This study provides insights as to how guidelines that are intended to promote responsible use of antibiotics in hospitals can be carefully developed to facilitate perceptions of relevance, transparency, and authority by health professionals.

An anthology: Rationale for a US ballistic missile defense (1969 - 1984)

NASA Astrophysics Data System (ADS)

Tircuit, E. C.

1985-04-01

This anthology is a selection and short synopsis of representative articles on the rationale for a US ballistic missile defense (BMD). Unclassified articles and documents were reviewed and analyzed to identify and include nine representative articles in the anthology. The anthology reduces the search for quality material on the subject and documents the fundamental rationale for a BMD. The author concluded that the fundamental rationale for a US BMD is to deter nuclear war. In addition, specific rationale for a US BMD is provided in the anthology. Finally, an extensive bibliography is included in the anthology to enhance further research on the subject.

Environment and Health in Children Day Care Centres (ENVIRH) - Study rationale and protocol.

PubMed

Araújo-Martins, J; Carreiro Martins, P; Viegas, J; Aelenei, D; Cano, M M; Teixeira, J P; Paixão, P; Papoila, A L; Leiria-Pinto, P; Pedro, C; Rosado-Pinto, J; Annesi-Maesano, I; Neuparth, N

2014-01-01

Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children's respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children's health. A building ventilation model will also be developed. This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC. Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Efficacy evaluation of an anti-caries varnish: protocol for a phase II randomised controlled trial

PubMed Central

Tut, Ohnmar; Rothen, Marilynn; Mancl, Lloyd; Gallen, Marcelle; Tanzer, Jason M

2017-01-01

Introduction Dental caries (tooth decay) is a common disease in which the products of sugar metabolism by certain bacteria that populate the tooth surface induce the development and progression of lesions (cavities). This is a phase II single-centre randomised, double-blind, active-controlled, parallel-group trial to assess the efficacy of a combination povidone iodine and sodium fluoride dental varnish to determine if it is superior to a varnish containing only sodium fluoride in the prevention of new caries lesions. The objective of this report is to describe the rationale and protocol for the trial. Methods and analysis The study site is Pohnpei State, Federated States of Micronesia. The study population is 284 children 48–84 months old. The primary outcome will be the surface-level primary molar caries increment (d2-3mfs/DMFS) at 2 years post baseline. The incremental dental caries at 1 year will also be compared between the two interventions. The secondary outcome is the Facial Image Scale after the initial treatment and after the fifth treatment at 1 year that gauges the child’s response to the treatment. Ethics and dissemination The Western Institutional Review Board (designated IRB) and the Institutional Review Board of the College of Micronesia-FSM approved all study procedures. The US Food and Drug Administration (FDA) has issued IND 128835 covering this study. The study results will be published and submitted to the FDA in support of a new drug application. Trialregistration number NCT03082196. PMID:28667230

Combustion: an oil spill mitigation tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1979-11-01

The technical feasibility of using combustion as an oil spill mitigation tool was studied. Part I of the two-part report is a practical guide oriented toward the needs of potential users, while Part II is the research or resource document from which the practical guidance was drawn. The study included theoretical evaluations of combustion of petroleum pool fires under the effects of weathering and an oil classification system related to combustion potential. The theoretical analysis of combustion is balanced by practical experience of oil burning and case history information. Decision elements are provided which can be used as a guidemore » for technical evaluations of a particular oil spill situation. The rationale for assessing technical feasibility is given in the context of other alternatives available for response to an oil spill. A series of research and technology development concepts are included for future research. The ethics of using oil burning are discussed as issues, concerns, and tradeoffs. A detailed annotated bibliography is appended along with a capsule review of a decade of oil burning studies and other support information.« less

Adhesives: Test Method, Group Assignment, and Categorization Guide for High-Loading Rate Applications - History and Rationale

DTIC Science & Technology

2017-04-20

Categorization Guide for High -Loading- Rate Applications – History and Rationale by Robert Jensen, David Flanagan, Daniel DeSchepper, and Charles...Adhesives: Test Method, Group Assignment, and Categorization Guide for High -Loading- Rate Applications – History and Rationale by Robert Jensen...Categorization Guide for High - Loading-Rate Applications – History and Rationale 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Reconceptualising the doctor-patient relationship: recognising the role of trust in contemporary health care.

PubMed

Bending, Zara J

2015-06-01

The conception of the doctor-patient relationship under Australian law has followed British common law tradition whereby the relationship is founded in a contractual exchange. By contrast, this article presents a rationale and framework for an alternative model-a "Trust Model"-for implementation into law to more accurately reflect the contemporary therapeutic dynamic. The framework has four elements: (i) an assumption that professional conflicts (actual or perceived) with patient safety, motivated by financial or personal interests, should be avoided; (ii) an onus on doctors to disclose these conflicts; (iii) a proposed mechanism to contend with instances where doctors choose not to disclose; and (iv) sanctions for non-compliance with the regime.

Innovation Related to the Tenure, Succession Pattern and Reference Group Orientation of the Principal. Final Report.

ERIC Educational Resources Information Center

Reynolds, James A.; Reynolds, Larry J.

The purposes of this study were to develop a conceptual rationale that might serve as the basis for a model of the change process and to test hypotheses derived from the rationale. It was believed that this approach would make a contribution to a growing body of research which views the school in the broader context of organizational theory. The…

Factors associated with opioid dose increases: a chart review of patients’ first year on long-term opioids

PubMed Central

Bautista, Christopher A.; Iosif, Ana-Maria; Wilsey, Barth L.; Melnikow, Joy A.; Crichlow, Althea; Henry, Stephen G.

2016-01-01

OBJECTIVE To examine encounter-level factors associated with opioid dose increases during patients’ first year on opioid therapy for chronic pain. DESIGN Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type; opioid dose change; documented prescribing rationale; documentation of guideline-concordant opioid prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. RESULTS 674 encounters were coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with email encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared to face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95%CI 0.11 – 0.28) and email (OR 0.23, 95%CI 0.12 – 0.47) encounters; documentation of prescribing rationale was significantly more likely for email (OR 5.06, 95%CI 1.87–13.72) and less likely for telephone (OR 0.30, 95%CI 0.18–0.51) encounters. CONCLUSION Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation. PMID:27477581

Small Changes and Lasting Effects (SCALE) Trial: The Formation of a Weight Loss Behavioral Intervention Using EVOLVE

PubMed Central

Phillips-Caesar, Erica G.; Winston, Ginger; Peterson, Janey C.; Wansink, Brian; Devine, Carol M.; Kanna, Balavanketsh; Michelin, Walid; Wethington, Elaine; Wells, Martin; Hollenberg, James; Charlson, Mary E.

2015-01-01

Background Obesity is a major health problem that disproportionately affects Black and Hispanic adults. This paper presents the rationale and innovative design of a small change eating and physical activity intervention (SC) combined with a positive affect and self-affirmation (PA/SA) intervention versus the SC intervention alone for weight loss. Methods Using a mixed methods translational model (EVOLVE), we designed and tested a SC approach intervention in overweight and/ or obese African American and Hispanic adults. In Phase I, we explored participant’s values and beliefs about the small change approach. In Phase II, we tested and refined the intervention and then, in Phase III we conducted a RCT. Participants were randomized to the SC approach with PA/SA intervention vs. a SC approach alone for 12 months. The primary outcome was clinically significant weight loss at 12 months. Results Over 4.5 years a total of 574 participants (67 in Phase I, 102 in Phase II and 405 in Phase III) were enrolled. Phase I findings were used to create a workbook based on real life experiences about weight loss and to refine the small change eating strategies. Phase II results shaped the recruitment and retention strategy for the RCT, as well as the final intervention. The RCT results are currently under analysis. Conclusion The present study seeks to determine if a SC approach combined with a PA/SA intervention will result in greater weight loss at 12 months in Black and Hispanic adults compared to a SC approach alone. PMID:25633208

Combined use of the Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF): a systematic review.

PubMed

Birken, Sarah A; Powell, Byron J; Presseau, Justin; Kirk, M Alexis; Lorencatto, Fabiana; Gould, Natalie J; Shea, Christopher M; Weiner, Bryan J; Francis, Jill J; Yu, Yan; Haines, Emily; Damschroder, Laura J

2017-01-05

Over 60 implementation frameworks exist. Using multiple frameworks may help researchers to address multiple study purposes, levels, and degrees of theoretical heritage and operationalizability; however, using multiple frameworks may result in unnecessary complexity and redundancy if doing so does not address study needs. The Consolidated Framework for Implementation Research (CFIR) and the Theoretical Domains Framework (TDF) are both well-operationalized, multi-level implementation determinant frameworks derived from theory. As such, the rationale for using the frameworks in combination (i.e., CFIR + TDF) is unclear. The objective of this systematic review was to elucidate the rationale for using CFIR + TDF by (1) describing studies that have used CFIR + TDF, (2) how they used CFIR + TDF, and (2) their stated rationale for using CFIR + TDF. We undertook a systematic review to identify studies that mentioned both the CFIR and the TDF, were written in English, were peer-reviewed, and reported either a protocol or results of an empirical study in MEDLINE/PubMed, PsycInfo, Web of Science, or Google Scholar. We then abstracted data into a matrix and analyzed it qualitatively, identifying salient themes. We identified five protocols and seven completed studies that used CFIR + TDF. CFIR + TDF was applied to studies in several countries, to a range of healthcare interventions, and at multiple intervention phases; used many designs, methods, and units of analysis; and assessed a variety of outcomes. Three studies indicated that using CFIR + TDF addressed multiple study purposes. Six studies indicated that using CFIR + TDF addressed multiple conceptual levels. Four studies did not explicitly state their rationale for using CFIR + TDF. Differences in the purposes that authors of the CFIR (e.g., comprehensive set of implementation determinants) and the TDF (e.g., intervention development) propose help to justify the use of CFIR + TDF. Given that the CFIR and the TDF are both multi-level frameworks, the rationale that using CFIR + TDF is needed to address multiple conceptual levels may reflect potentially misleading conventional wisdom. On the other hand, using CFIR + TDF may more fully define the multi-level nature of implementation. To avoid concerns about unnecessary complexity and redundancy, scholars who use CFIR + TDF and combinations of other frameworks should specify how the frameworks contribute to their study. PROSPERO CRD42015027615.

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

33 CFR 279.9 - Objective rationale.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 279.9 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE RESOURCE USE: ESTABLISHMENT OF OBJECTIVES § 279.9 Objective rationale. (a) Statement of objectives... objective(s) and providing the rationale, impact, and basic management measures for their accomplishment...

Insights into the crystal-packing effects on the spin crossover of [Fe(II)(1-bpp)](2+)-based materials.

PubMed

Vela, Sergi; Novoa, Juan J; Ribas-Arino, Jordi

2014-12-28

Iron(II) complexes of the [Fe(II)(1-bpp2)](2+) type (1-bpp = 2,6-di(pyrazol-1-yl)pyridine) have been intensively investigated in the context of crystal engineering of switchable materials because their spin-crossover (SCO) properties dramatically depend on the counterions. Here, by means of DFT + U calculations at the molecular and solid state levels we provide a rationale for the different SCO behaviour of the BF4(-) and ClO4(-) salts of the parent complex; the former features Fe(II) complexes with a regular coordination geometry and undergoes a spin transition, whereas the Fe(II) complexes of the latter adopt a distorted structure and remain in the high-spin state at all temperatures. The different SCO behaviour of both salts can be explained on the basis of a combination of thermodynamic and kinetic effects. The shape of the SCO units at high temperature is thermodynamically controlled by the intermolecular interactions between the SCO units and counterions within the crystal. The spin trapping at low temperatures in the ClO4(-) salt, in turn, is traced back to a kinetic effect because our calculations have revealed the existence of a more stable polymorph having SCO units in their low-spin state that feature a regular structure. From the computational point of view, it is the first time that the U parameter is fine-tuned on the basis of CASPT2 calculations, thereby enabling an accurate description of the energetics of the spin transition at both molecular and solid-state levels.

Changing Rationales for Governing the Child: A Historical Perspective on the Emergence of the Psychological Child in the Context of Preschool--Notes on a Study in Progress.

ERIC Educational Resources Information Center

Hultqvist, Kenneth

1997-01-01

Focuses on the issue of change in preschool discourse and argues that changes are related to the emergence of new rationales for governing the child. Specifically describes a period of transition (1920-1940) in the history of the Swedish preschool when Friedrich Froebel's discourse on the child became replaced by developmental psychology. (SD)

Tyrosyl-DNA phosphodiesterase inhibitors: Progress and potential.

PubMed

Laev, Sergey S; Salakhutdinov, Nariman F; Lavrik, Olga I

2016-11-01

DNA topoisomerases are essential during transcription and replication. The therapeutic mechanism of action of topoisomerase inhibitors is enzyme poisoning rather than catalytic inhibition. Tyrosyl-DNA phosphodiesterases 1 or 2 were found as DNA repair enzymes hydrolyzing the covalent bond between the tyrosyl residue of topoisomerases I or II and the 3'- or 5'-phosphate groups in DNA, respectively. Tyrosyl-DNA phosphodiesterase 1 is a key enzyme in DNA repair machinery and a promising target for antitumor and neurodegenerative therapy. Inhibitors of tyrosyl-DNA phosphodiesterase 1 could act synergistically with topoisomerase I inhibitors and thereby potentiate the effects of topoisomerase I poisons. Tyrosyl-DNA phosphodiesterase 2 is an enzyme that specifically repairs DNA damages induced by topoisomerase II poisons and causes resistance to these drugs. Selective inhibition of tyrosyl-DNA phosphodiesterase 2 may be a novel approach to overcome intrinsic or acquired resistance to topoisomerase II-targeted drug therapy. Thus, agents that inhibit tyrosyl-DNA phosphodiesterases 1 and 2 have many applications in biochemical and physiological research and they have the potential to become anticancer and antiviral drugs. The structures, mechanism of action and therapeutic rationale of tyrosyl-DNA phosphodiesterase inhibitors and their development for combinations with topoisomerase inhibitors and DNA damaging agents are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-acting antiviral agents for HIV treatment

PubMed Central

Margolis, David A.; Boffito, Marta

2015-01-01

Purpose of review Long-acting antiretroviral (ARV) agents are currently under development for the treatment of chronic HIV infection. This review focuses on data recently produced on injectable ARVs for patients living with HIV/AIDS and on the patients’ perspectives on the use of these agents. Recent findings Crystalline nanoparticle formulations of the nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) and of the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) have progressed into phase II clinical trials as injectable maintenance therapy for patients living with HIV/AIDS with an undetectable viral load. Summary Phase II studies evaluating the coadministration of rilpivirine and cabotegravir intramuscularly to HIV-infected individuals with an undetectable viral load are currently underway. Rilpivirine and cabotegravir are characterized by different mechanisms of action against HIV and a favorable drug interaction profile, providing a rationale for coadministration. The high potency and low daily dosing requirements of oral cabotegravir and rilpivirine facilitate long-acting formulation development. Intramuscular dosing is preceded by an oral lead-in phase to assess safety and tolerability in individual participants. In addition to assessing the safety of injectable therapies in ongoing studies, it will be important to evaluate whether differences in drug adherence between injectable and oral therapies lead to different virologic outcomes, including rates of virologic failure and the emergence of resistance. Long-acting formulations may be associated with challenges, such as the management of adverse effects with persistent drug concentrations and the risk of virologic resistance, as drug concentrations decline following discontinuation. PMID:26049949

Stakeholders' expectations and perceived effects of the pharmacy ownership liberalization reform in Sweden: a qualitative interview study.

PubMed

Wisell, Kristin; Winblad, Ulrika; Sporrong, Sofia Kälvemark

2016-08-12

Reforms in the health-care sector, including the pharmacy sector, can have different rationales. The Swedish pharmacies were prior to 2009 organized in a state-owned monopoly. In 2009, a liberalization of the ownership took place, in which a majority of the pharmacies were sold to private owners. The rationales for this liberalization changed profoundly during the preparatory work, making it probable that other rationales than the ones first expressed existed. The aim of this study was to explore the underlying rationales (not stated in official documents) for the liberalization in the Swedish pharmacy sector, and also to compare the expectations with the perceived outcomes. Semi-structured interviews were conducted with representatives from key stakeholder organizations; i.e., political, patient, and professional organizations. The analysis was performed in steps, and themes were developed in an inductive manner. One expectation among the political organization participants was that the ownership liberalization would create opportunities for ideas. The competition introduced in the market was supposed to lead to a more diversified pharmacy sector. After the liberalization, the participants in favor of the liberalization were surprised that the pharmacies were so similar. Among the professional organization participants, one important rationale for the liberalization was to get better use of the pharmacists' knowledge. However, all the professional, and some of the patient organization participants, thought that the counseling in the pharmacies had deteriorated after the liberalization. As expected in the interviews, the post-liberalization pharmacy sector consists of more pharmacies. However, an unexpected perceived effect of the liberalization was, among participants from all the stakeholder groups, less access to prescription medicines in the pharmacies. This study showed that the political organization participants had an ideological basis for their opinion. The political stakeholders did not have a clear view about what the liberalization should lead to, apart from abolishing the monopoly. The perceived effects are quite similar in the different stakeholder groups, and not as positive as were expected.

Exploring metabolic dysfunction in chronic kidney disease

PubMed Central

2012-01-01

Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid receptor. Insight into the multiple factors altered in CKD may provide useful information on disease pathogenesis, clinical assessment and treatment rationale such as potential pharmacological, nutritional and exercise therapies. PMID:22537670

Reliability and validity: Part II.

PubMed

Davis, Debora Winders

2004-01-01

Determining measurement reliability and validity involves complex processes. There is usually room for argument about most instruments. It is important that the researcher clearly describes the processes upon which she made the decision to use a particular instrument, and presents the evidence available showing that the instrument is reliable and valid for the current purposes. In some cases, the researcher may need to conduct pilot studies to obtain evidence upon which to decide whether the instrument is valid for a new population or a different setting. In all cases, the researcher must present a clear and complete explanation for the choices, she has made regarding reliability and validity. The consumer must then judge the degree to which the researcher has provided adequate and theoretically sound rationale. Although I have tried to touch on most of the important concepts related to measurement reliability and validity, it is beyond the scope of this column to be exhaustive. There are textbooks devoted entirely to specific measurement issues if readers require more in-depth knowledge.

Bagging Voronoi classifiers for clustering spatial functional data

NASA Astrophysics Data System (ADS)

Secchi, Piercesare; Vantini, Simone; Vitelli, Valeria

2013-06-01

We propose a bagging strategy based on random Voronoi tessellations for the exploration of geo-referenced functional data, suitable for different purposes (e.g., classification, regression, dimensional reduction, …). Urged by an application to environmental data contained in the Surface Solar Energy database, we focus in particular on the problem of clustering functional data indexed by the sites of a spatial finite lattice. We thus illustrate our strategy by implementing a specific algorithm whose rationale is to (i) replace the original data set with a reduced one, composed by local representatives of neighborhoods covering the entire investigated area; (ii) analyze the local representatives; (iii) repeat the previous analysis many times for different reduced data sets associated to randomly generated different sets of neighborhoods, thus obtaining many different weak formulations of the analysis; (iv) finally, bag together the weak analyses to obtain a conclusive strong analysis. Through an extensive simulation study, we show that this new procedure - which does not require an explicit model for spatial dependence - is statistically and computationally efficient.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat.

PubMed

Gandhi, M; Aggarwal, M; Puri, S; Singla, S K

2013-01-01

Many medicinal plants have been employed during ages to treat urinary stones though the rationale behind their use is not well established. Thus, the present study was proposed to evaluate the effect of coconut water as a prophylactic agent in experimentally induced nephrolithiasis in a rat model. The male Wistar rats were divided randomly into three groups. Animals of group I (control) were fed standard rat diet. In group II, the animals were administrated 0.75% ethylene glycol in drinking water for the induction of nephrolithiasis. Group III animals were administrated coconut water in addition to ethylene glycol. All the treatments were continued for a total duration of seven weeks. Treatment with coconut water inhibited crystal deposition in renal tissue as well as reduced the number of crystals in urine. Furthermore, coconut water also protected against impaired renal function and development of oxidative stress in the kidneys. The results indicate that coconut water could be a potential candidate for phytotherapy against urolithiasis.

Forum: The Rise of International Large-Scale Assessments and Rationales for Participation

ERIC Educational Resources Information Center

Addey, Camilla; Sellar, Sam; Steiner-Khamsi, Gita; Lingard, Bob; Verger, Antoni

2017-01-01

This Forum discusses the significant growth of international large-scale assessments (ILSAs) since the mid-1990s. Addey and Sellar's contribution ("A Framework for Analysing the Multiple Rationales for Participating in International Large-Scale Assessments") outlines a framework of rationales for participating in ILSAs and examines the…

The Social Benefits of Higher Education: Implications for Regional Finance.

ERIC Educational Resources Information Center

Winkler, Donald R.

This paper evaluates the nature, size, and distribution of public benefits generated by institutions of higher education and assesses the rationale for regional subsidies. Following introductory material, part two discusses the rationale for general public support of higher education and assesses the legitimacy of extending this rationale to…

"Socialized Music": Historical Formations of Community Music through Social Rationales

ERIC Educational Resources Information Center

Yerichuk, Deanna

2014-01-01

This article traces the formation of community music through professional and scholarly articles over the last century in North America, and argues that community music has been discursively formed through social rationales, although the specific rationales have shifted. The author employs an archaeological framework inspired by Michel Foucault to…

Evaluation of the Wound Healing Potential of Resina Draconis (Dracaena cochinchinensis) in Animal Models.

PubMed

Liu, Huihui; Lin, Shaohui; Xiao, Dan; Zheng, Xiao; Gu, Yan; Guo, Shanyu

2013-01-01

Resina Draconis (RD) is a type of dragon's blood resin obtained from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). It has been used as a medicine since ancient times by many cultures. The ethanolic extract of Resina Draconis (RDEE) was evaluated for its wound-healing activity using excision and incision wound models in rats. Group I, the control group, was treated with ointment base. Group II, which served as a reference standard, was treated with moist exposed burn ointment (MEBO). Group III was treated with RDEE. The parameters observed were percentage of wound contraction, epithelialization period, tensile strength, histopathological studies, microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and transforming growth factor- β 1 (TGF- β 1). The group treated with RDEE showed significantly better wound contraction and better skin-breaking strength as compared with the control group. The results of histopathological examination, MVD, and the expression levels of growth factors supported the outcome of the wound models as well. The present study provided a scientific rationale for the traditional use of RD in the management of wounds.

Evaluation of the Wound Healing Potential of Resina Draconis (Dracaena cochinchinensis) in Animal Models

PubMed Central

Gu, Yan

2013-01-01

Resina Draconis (RD) is a type of dragon's blood resin obtained from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). It has been used as a medicine since ancient times by many cultures. The ethanolic extract of Resina Draconis (RDEE) was evaluated for its wound-healing activity using excision and incision wound models in rats. Group I, the control group, was treated with ointment base. Group II, which served as a reference standard, was treated with moist exposed burn ointment (MEBO). Group III was treated with RDEE. The parameters observed were percentage of wound contraction, epithelialization period, tensile strength, histopathological studies, microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). The group treated with RDEE showed significantly better wound contraction and better skin-breaking strength as compared with the control group. The results of histopathological examination, MVD, and the expression levels of growth factors supported the outcome of the wound models as well. The present study provided a scientific rationale for the traditional use of RD in the management of wounds. PMID:23762154

[Microbiological rationale for using whey on salting salmon caviar].

PubMed

Kim, I N; Shtan'ko, T I

2011-01-01

The paper provides a rationale for the use of whey to salt salmon fishes instead of traditional preservatives, including those exported from low industrial potential countries, which do not undergo comprehensive sanitary and hygienic tests. On the basis of the performed studies, the authors recommend to use whey to salt salmon caviar, which ensures the ecological purity of the product containing the minimum amount of preservatives and other substances that fail to affect its organoleptic properties.

Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes.

PubMed

Stienen, Susan; Salah, Khibar; Moons, Andreas H M; Bakx, Adrianus L M; van Pol, Petra E; Schroeder-Tanka, Jutta M; Voogel, Albertus J; Keijer, Jan T; Kortz, R A Mikael; Dickhoff, Cathelijne; Meregalli, Paola G; Tijssen, Jan G; Pinto, Yigal M; Kok, Wouter E

2014-07-01

Hospital admissions for acute decompensated heart failure (ADHF) are frequent and are accompanied by high percentages of mortality and readmissions. Brain natriuretic peptide (BNP) and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP) are currently the best predictors of prognosis in heart failure (HF) patients. In the setting of chronic HF, studies that performed guidance of therapy by NT-proBNP have had only limited success. For patients with ADHF, retrospective studies have shown that a reduction in NT-proBNP of ≤30% during admission is a significant predictor of HF readmissions and mortality. These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions. The PRIMA II is an investigator-initiated, multicenter, randomized, controlled, prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction during admission) on the reduction of readmission and mortality rates within 180 days. Consenting ADHF patients with NT-proBNP levels of >1,700 ng/L are eligible. After achieving clinical stability, a total of 340 patients are randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point is dual, that is, a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days. Secondary end points are readmissions and/or mortality in 180 days, cost effectiveness of hospitalization days in 180 days, readmissions and mortality in 90 days, and quality of life. The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADHF. Copyright © 2014 Mosby, Inc. All rights reserved.

Clickers or Flashcards: Is There Really a Difference?

NASA Astrophysics Data System (ADS)

Lasry, N.

2008-04-01

A growing number of physics teachers are currently turning to instructional technologies such as wireless handheld response systems—colloquially called clickers. Two possible rationales may explain the growing interest in these devices. The first is the presumption that clickers are more effective instructional instruments. The second rationale is somewhat reminiscent of Martin Davis' declaration when purchasing the Oakland Athletics: "As men get older, the toys get more expensive." Although personally motivated by both of these rationales, the effectiveness of clickers over inexpensive low-tech flashcards remains questionable. Thus, the first half of this paper presents findings of a classroom study comparing the differences in student learning between a Peer Instruction group using clickers and a Peer Instruction group using flashcards. Having assessed student learning differences, the second half of the paper describes differences in teaching effectiveness between clickers and flashcards.

Planckian Information (Ip): A New Measure of Order in Atoms, Enzymes, Cells, Brains, Human Societies, and the Cosmos

NASA Astrophysics Data System (ADS)

Ji, Sungchul

A new mathematical formula referred to as the Planckian distribution equation (PDE) has been found to fit long-tailed histograms generated in various fields of studies, ranging from atomic physics to single-molecule enzymology, cell biology, brain neurobiology, glottometrics, econophysics, and to cosmology. PDE can be derived from a Gaussian-like equation (GLE) by non-linearly transforming its variable, x, while keeping the y coordinate constant. Assuming that GLE represents a random distribution (due to its symmetry), it is possible to define a binary logarithm of the ratio between the areas under the curves of PDE and GLE as a measure of the non-randomness (or order) underlying the biophysicochemical processes generating long-tailed histograms that fit PDE. This new function has been named the Planckian information, IP, which (i) may be a new measure of order that can be applied widely to both natural and human sciences and (ii) can serve as the opposite of the Boltzmann-Gibbs entropy, S, which is a measure of disorder. The possible rationales for the universality of PDE may include (i) the universality of the wave-particle duality embedded in PDE, (ii) the selection of subsets of random processes (thereby breaking the symmetry of GLE) as the basic mechanism of generating order, organization, and function, and (iii) the quantity-quality complementarity as the connection between PDE and Peircean semiotics.

The use of schools for malaria surveillance and programme evaluation in Africa

PubMed Central

Brooker, Simon; Kolaczinski, Jan H; Gitonga, Carol W; Noor, Abdisalan M; Snow, Robert W

2009-01-01

Effective malaria control requires information on both the geographical distribution of malaria risk and the effectiveness of malaria interventions. The current standard for estimating malaria infection and impact indicators are household cluster surveys, but their complexity and expense preclude frequent and decentralized monitoring. This paper reviews the historical experience and current rationale for the use of schools and school children as a complementary, inexpensive framework for planning, monitoring and evaluating malaria control in Africa. Consideration is given to (i) the selection of schools; (ii) diagnosis of infection in schools; (iii) the representativeness of schools as a proxy of the communities they serve; and (iv) the increasing need to evaluate interventions delivered through schools. Finally, areas requiring further investigation are highlighted. PMID:19840372

Ex vivo lung perfusion.

PubMed

Reeb, Jeremie; Cypel, Marcelo

2016-03-01

Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Moral and Instrumental Rationales for Affirmative Action in Five National Contexts

ERIC Educational Resources Information Center

Moses, Michele S.

2010-01-01

The author's primary aims are to clarify the differing rationales for affirmative action that have emerged in five nations--France, India, South Africa, the United States, and Brazil--and to make the case for the most compelling rationales, whether instrumentally or morally based. She examines the different social contexts surrounding the…

Rationales for Challenged Books. [CD-ROM].

ERIC Educational Resources Information Center

National Council of Teachers of English, Urbana, IL.

This CD-ROM presents a collection of over 200 rationales for over 170 works (mainly novels but a few films) for use by teachers combating censorship. Some rationales on the disc are from published sources; others are student papers. Although the materials in the collection range from kindergarten through grade 12, the emphasis is on the middle…

Structural and Functional insights into the catalytic mechanism of the Type II NADH:quinone oxidoreductase family

PubMed Central

Marreiros, Bruno C.; Sena, Filipa V.; Sousa, Filipe M.; Oliveira, A. Sofia F.; Soares, Cláudio M.; Batista, Ana P.; Pereira, Manuela M.

2017-01-01

Type II NADH:quinone oxidoreductases (NDH-2s) are membrane proteins involved in respiratory chains. These proteins contribute indirectly to the establishment of the transmembrane difference of electrochemical potential by catalyzing the reduction of quinone by oxidation of NAD(P)H. NDH-2s are widespread enzymes being present in the three domains of life. In this work, we explored the catalytic mechanism of NDH-2 by investigating the common elements of all NDH-2s, based on the rationale that conservation of such elements reflects their structural/functional importance. We observed conserved sequence motifs and structural elements among 1762 NDH-2s. We identified two proton pathways possibly involved in the protonation of the quinone. Our results led us to propose the first catalytic mechanism for NDH-2 family, in which a conserved glutamate residue, E172 (in NDH-2 from Staphylococcus aureus) plays a key role in proton transfer to the quinone pocket. This catalytic mechanism may also be extended to the other members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, such as sulfide:quinone oxidoreductases. PMID:28181562

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal

PubMed Central

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-01-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a non­canonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided. PMID:25478840

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

PubMed

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-12-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

PubMed

Giles, Thomas D; Cockcroft, John R; Pitt, Bertram; Jakate, Abhijeet; Wright, Harold M

2017-09-01

: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes.

PubMed

Yamaguchi, Hironori; Kitayama, Joji; Ishigami, Hironori; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Ishihara, Soichiro; Sunami, Eiji; Watanabe, Toshiaki

2015-11-15

The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Rationale, design, and methodology for the optimizing outcomes in women with gestational diabetes mellitus and their infants study.

PubMed

Berry, Diane C; Neal, Madeline; Hall, Emily G; Schwartz, Todd A; Verbiest, Sarah; Bonuck, Karen; Goodnight, William; Brody, Seth; Dorman, Karen F; Menard, Mary K; Stuebe, Alison M

2013-10-10

Women who are diagnosed with gestational diabetes mellitus (GDM) are at increased risk for developing prediabetes and type 2 diabetes mellitus (T2DM). To date, there have been few interdisciplinary interventions that target predominantly ethnic minority low-income women diagnosed with GDM. This paper describes the rationale, design and methodology of a 2-year, randomized, controlled study being conducted in North Carolina. Using a two-group, repeated measures, experimental design, we will test a 14- week intensive intervention on the benefits of breastfeeding, understanding gestational diabetes and risk of progression to prediabetes and T2DM, nutrition and exercise education, coping skills training, physical activity (Phase I), educational and motivational text messaging and 3 months of continued monthly contact (Phase II). A total of 100 African American, non-Hispanic white, and bilingual Hispanic women between 22-36 weeks of pregnancy who are diagnosed with GDM and their infants will be randomized to either the experimental group or the wait-listed control group. The first aim of the study is to determine the feasibility of the intervention. The second aim of study is to test the effects of the intervention on maternal outcomes from baseline (22-36 weeks pregnant) to 10 months postpartum. Primary maternal outcomes will include fasting blood glucose and weight (BMI) from baseline to 10 months postpartum. Secondary maternal outcomes will include clinical, adiposity, health behaviors and self-efficacy outcomes from baseline to 10 months postpartum. The third aim of the study is to quantify the effects of the intervention on infant feeding and growth. Infant outcomes will include weight status and breastfeeding from birth through 10 months of age. Data analysis will include general linear mixed-effects models. Safety endpoints include adverse event reporting. Findings from this trial may lead to an effective intervention to assist women diagnosed with GDM to improve maternal glucose homeostasis and weight as well as stabilize infant growth trajectory, reducing the burden of metabolic disease across two generations. NCT01809431.

Rationale, design, and methodology for the optimizing outcomes in women with gestational diabetes mellitus and their infants study

PubMed Central

2013-01-01

Background Women who are diagnosed with gestational diabetes mellitus (GDM) are at increased risk for developing prediabetes and type 2 diabetes mellitus (T2DM). To date, there have been few interdisciplinary interventions that target predominantly ethnic minority low-income women diagnosed with GDM. This paper describes the rationale, design and methodology of a 2-year, randomized, controlled study being conducted in North Carolina. Methods/Design Using a two-group, repeated measures, experimental design, we will test a 14- week intensive intervention on the benefits of breastfeeding, understanding gestational diabetes and risk of progression to prediabetes and T2DM, nutrition and exercise education, coping skills training, physical activity (Phase I), educational and motivational text messaging and 3 months of continued monthly contact (Phase II). A total of 100 African American, non-Hispanic white, and bilingual Hispanic women between 22–36 weeks of pregnancy who are diagnosed with GDM and their infants will be randomized to either the experimental group or the wait-listed control group. The first aim of the study is to determine the feasibility of the intervention. The second aim of study is to test the effects of the intervention on maternal outcomes from baseline (22–36 weeks pregnant) to 10 months postpartum. Primary maternal outcomes will include fasting blood glucose and weight (BMI) from baseline to 10 months postpartum. Secondary maternal outcomes will include clinical, adiposity, health behaviors and self-efficacy outcomes from baseline to 10 months postpartum. The third aim of the study is to quantify the effects of the intervention on infant feeding and growth. Infant outcomes will include weight status and breastfeeding from birth through 10 months of age. Data analysis will include general linear mixed-effects models. Safety endpoints include adverse event reporting. Discussion Findings from this trial may lead to an effective intervention to assist women diagnosed with GDM to improve maternal glucose homeostasis and weight as well as stabilize infant growth trajectory, reducing the burden of metabolic disease across two generations. Trial registration NCT01809431 PMID:24112417

Life sciences interests in Mars missions

NASA Technical Reports Server (NTRS)

Rummel, John D.; Griffiths, Lynn D.

1989-01-01

NASA's Space Life Sciences research permeates plans for Mars missions and the rationale for the exploration of the planet. The Space Life Sciences program has three major roles in Mars mission studies: providing enabling technology for piloted missions, conducting scientific exploration related to the origin and evolution of life, and protecting space crews from the adverse physiological effects of space flight. This paper presents a rationale for exploration and some of the issues, tradeoffs, and visions being addressed in the Space Life Sciences program in preparation for Mars missions.

A randomized controlled trial to evaluate self-determination theory for exercise adherence and weight control: rationale and intervention description

PubMed Central

Silva, Marlene N; Markland, David; Minderico, Cláudia S; Vieira, Paulo N; Castro, Margarida M; Coutinho, Sílvia R; Santos, Teresa C; Matos, Margarida G; Sardinha, Luís B; Teixeira, Pedro J

2008-01-01

Background Research on the motivational model proposed by Self-Determination Theory (SDT) provides theoretically sound insights into reasons why people adopt and maintain exercise and other health behaviors, and allows for a meaningful analysis of the motivational processes involved in behavioral self-regulation. Although obesity is notoriously difficult to reverse and its recidivism is high, adopting and maintaining a physically active lifestyle is arguably the most effective strategy to counteract it in the long-term. The purposes of this study are twofold: i) to describe a 3-year randomized controlled trial (RCT) aimed at testing a novel obesity treatment program based on SDT, and ii) to present the rationale behind SDT's utility in facilitating and explaining health behavior change, especially physical activity/exercise, during obesity treatment. Methods Study design, recruitment, inclusion criteria, measurements, and a detailed description of the intervention (general format, goals for the participants, intervention curriculum, and main SDT strategies) are presented. The intervention consists of a 1-year group behavioral program for overweight and moderately obese women, aged 25 to 50 (and pre-menopausal), recruited from the community at large through media advertisement. Participants in the intervention group meet weekly or bi-weekly with a multidisciplinary intervention team (30 2 h sessions in total), and go through a program covering most topics considered critical for successful weight control. These topics and especially their delivery were adapted to comply with SDT and Motivational Interviewing guidelines. Comparison group receive a general health education curriculum. After the program, all subjects are follow-up for a period of 2 years. Discussion Results from this RCT will contribute to a better understanding of how motivational characteristics, particularly those related to physical activity/exercise behavioral self-regulation, influence treatment success, while exploring the utility of Self-Determination Theory for promoting health behavior change in the context of obesity. Trial Registration Clinical Trials Gov. Identifier NCT00513084 PMID:18613959

Pediatric endurance and limb strengthening for children with cerebral palsy (PEDALS) – a randomized controlled trial protocol for a stationary cycling intervention

PubMed Central

Fowler, Eileen G; Knutson, Loretta M; DeMuth, Sharon K; Sugi, Mia; Siebert, Kara; Simms, Victoria; Azen, Stanley P; Winstein, Carolee J

2007-01-01

Background In the past, effortful exercises were considered inappropriate for children with spastic cerebral palsy (CP) due to concern that they would escalate abnormalities including spasticity and abnormal movement patterns. Current scientific evidence indicates that these concerns were unfounded and that therapeutic interventions focused on muscle strengthening can lead to improved functional ability. However, few studies have examined the potential benefits of cardiorespiratory fitness exercises in this patient population. Methods/design The rationale and design of a randomized controlled trial examining the effects of a stationary cycling intervention for children with CP are outlined here. Sixty children with spastic diplegic CP between the ages of 7 and 18 years and Gross Motor Function Classification System (GMFCS) levels of I, II, or III will be recruited for this study. Participants will be randomly assigned to either an intervention (cycling) or a control (no cycling) group. The cycling intervention will be divided into strengthening and cardiorespiratory endurance exercise phases. During the strengthening phase, the resistance to lower extremity cycling will be progressively increased using a uniquely designed limb-loaded mechanism. The cardiorespiratory endurance phase will focus on increasing the intensity and duration of cycling. Children will be encouraged to exercise within a target heart rate (HR) range (70 – 80% maximum HR). Thirty sessions will take place over a 10–12 week period. All children will be evaluated before (baseline) and after (follow-up) the intervention period. Primary outcome measures are: knee joint extensor and flexor moments, or torque; the Gross Motor Function Measure (GMFM); the 600 Yard Walk-Run test and the Thirty-Second Walk test (30 sec WT). Discussion This paper presents the rationale, design and protocol for Pediatric Endurance and Limb Strengthening (PEDALS); a Phase I randomized controlled trial evaluating the efficacy of a stationary cycling intervention for children with spastic diplegic cerebral palsy. PMID:17374171

Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy

PubMed Central

Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M.; Scott, Robert; Sabatine, Marc S.

2013-01-01

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60–80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein’s role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C–lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy–Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. PMID:22714699

A Rationale for Building a Comprehensive Science Program for Inner-City Education.

ERIC Educational Resources Information Center

Martin, Charles Arthur

The intent of this dissertation was to develop a science curriculum from an inner-city perspective. Five units and a rationale for inner-city education are included. The units include both physical and biological science topics. The units are as follows: (1) Rationale for Building a Comprehensive Science Program for Inner-City Education; (2) With…

Soft Power as a Policy Rationale for International Education in the UK: A Critical Analysis

ERIC Educational Resources Information Center

Lomer, Sylvie

2017-01-01

This article presents the results of a textual analysis conducted on policy discourses on international students in the UK between 1999 and 2013. A number of rationales for and against increasing their numbers have been made, which have largely remained consistent over changing political administrations. One key rationale is that international…

The introduction of anti-HTLV testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006.

PubMed

Davison, K L; Dow, B; Barbara, J A; Hewitt, P E; Eglin, R

2009-02-01

The objectives of the study were to describe the introduction of testing blood donations for antibodies to human T-cell lymphotropic virus (anti-HTLV) and to determine the risk of HTLV potentially infectious donations entering the UK blood supply. The rationale for testing was based on (i) evidence of transmission through transfusion in the UK, (ii) the serious nature of HTLV I-associated morbidity and (iii) evidence of infection in UK blood donors. From mid-2002, all blood donations made at UK blood centres were tested in pooled samples using Abbott-Murex HTLV I/II GE 80/81 enzyme immunoassay (EIA). Surveillance data were used to calculate the incidence and prevalence of anti-HTLV and derive estimates of risk. Between August 2002 and December 2006, 106 donations were confirmed positive for anti-HTLV (95 anti-HTLV I and 11 anti-HTLV II). Prevalence was 10-fold higher among donations from new donors than repeat (4.0 and 0.42 per 100 000 donations), and only one repeat donor had evidence of seroconversion. The risk of an HTLV I potentially infectious donation entering the UK blood supply was estimated at 0.11 per million donations (95% confidence interval 0.06 to 0.18). The current very low observed incidence and prevalence among blood donors reflect the very low estimated risk of an HTLV I-positive donation entering the UK blood supply. A change in either the epidemiology of HTLV in UK blood donors or the length of the window period of the test should prompt further review of the risk and a reassessment of anti-HTLV testing in the UK.

Factors associated with failure of oncology drugs in late-stage clinical development: A systematic review.

PubMed

Jardim, Denis L; Groves, Eric S; Breitfeld, Philip P; Kurzrock, Razelle

2017-01-01

We aimed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development. We searched the PharmaProjects database (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials, but never gained Food and Drug Administration (FDA) approval were compared to 37 anti-cancer drugs achieving FDA approval in this time period. Forty-two drugs fit our criteria for development failures. These failed drugs (49% targeted, 23% cytotoxics, and 28% other) were tested in 43 cancer indications (drug programs). Only 16% (7/43) of failed drug programs adopted a biomarker-driven rationale for patient selection versus 57% (21/37) of successful drug programs (P<0.001). Phase II trial information was available in 32 of 43 failed drug programs and in 32 of 37 successful programs. Nine of the 32 trials (28%) of failed drugs versus 28 of 32 trials (87%) of successful drugs (P<0.001) achieved proof of concept (single agent response rate (RR) ⩾20% or combination therapy showing a ⩾20% RR increase above the median historical RR without the experimental agent (with a minimal absolute increase of 5%) or a randomized phase II trial showing significance (P⩽0.05) for its primary outcome). No pattern of study sites, trial design or funding characteristics emerged from the failed drug analysis. For drugs that reached Phase III, lack of a biomarker-driven strategy and failure to attain proof of concept in phase II are potential risk factors for later discontinuation, especially for targeted agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combined angiotensin receptor/neprilysin inhibitors: a review of the new paradigm in the management of chronic heart failure.

PubMed

Macdonald, Peter S

2015-10-01

The aims of this article were to review the rationale behind the development of combined angiotensin receptor/neprilysin inhibitors (ARNIs) for the management of chronic heart failure (HF) and to review the major clinical trials of LCZ696, the first drug in this class, that have been conducted to date. A selected review was undertaken of publications examining the preclinical and clinical studies of drugs aimed at enhancing the activity of the endogenous natriuretic peptide system and their combination with inhibitors of the renin-angiotensin-aldosterone system, initially angiotensin-converting enzyme inhibitors (ACEIs) and more recently angiotensin II type 1 receptor blockers. Selective neprilysin inhibitors are unlikely to be of benefit and may be associated with adverse effects when used in isolation in HF. Combining NIs with ACEIs is unsafe because of an unacceptably high prevalence of angioedema, which may be mediated by elevated levels of endogenous bradykinin. Combining a neprilysin inhibitor with an angiotensin II type 1 receptor blockers avoids the risk for angioedema. The ARNI LCZ696 was associated with greater reductions both mortality and morbidity compared with those with enalapril in a large-scale, Phase III clinical trial in patients with HF with reduced ejection fraction. Findings from a Phase II clinical trial suggested that LCZ696 may also be beneficial in HF with preserved ejection fraction, and a Phase III clinical trial of LCZ696 used for this indication is under way. ARNIs have been described as a "game changer" by cardiologists. Based on findings from clinical trials conducted to date, there is an expectation that they will replace ACEIs as a building block of the pharmacologic treatment of chronic HF. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Ontology-based configuration of problem-solving methods and generation of knowledge-acquisition tools: application of PROTEGE-II to protocol-based decision support.

PubMed

Tu, S W; Eriksson, H; Gennari, J H; Shahar, Y; Musen, M A

1995-06-01

PROTEGE-II is a suite of tools and a methodology for building knowledge-based systems and domain-specific knowledge-acquisition tools. In this paper, we show how PROTEGE-II can be applied to the task of providing protocol-based decision support in the domain of treating HIV-infected patients. To apply PROTEGE-II, (1) we construct a decomposable problem-solving method called episodic skeletal-plan refinement, (2) we build an application ontology that consists of the terms and relations in the domain, and of method-specific distinctions not already captured in the domain terms, and (3) we specify mapping relations that link terms from the application ontology to the domain-independent terms used in the problem-solving method. From the application ontology, we automatically generate a domain-specific knowledge-acquisition tool that is custom-tailored for the application. The knowledge-acquisition tool is used for the creation and maintenance of domain knowledge used by the problem-solving method. The general goal of the PROTEGE-II approach is to produce systems and components that are reusable and easily maintained. This is the rationale for constructing ontologies and problem-solving methods that can be composed from a set of smaller-grained methods and mechanisms. This is also why we tightly couple the knowledge-acquisition tools to the application ontology that specifies the domain terms used in the problem-solving systems. Although our evaluation is still preliminary, for the application task of providing protocol-based decision support, we show that these goals of reusability and easy maintenance can be achieved. We discuss design decisions and the tradeoffs that have to be made in the development of the system.

Cognitive defusion versus thought distraction: a clinical rationale, training, and experiential exercise in altering psychological impacts of negative self-referential thoughts.

PubMed

Masuda, Akihiko; Feinstein, Amanda B; Wendell, Johanna W; Sheehan, Shawn T

2010-11-01

Using two modes of intervention delivery, the present study compared the effects of a cognitive defusion strategy with a thought distraction strategy on the emotional discomfort and believability of negative self-referential thoughts. One mode of intervention delivery consisted of a clinical rationale and training (i.e., Partial condition). The other mode contained a condition-specific experiential exercise with the negative self-referential thought in addition to the clinical rationale and training (i.e., Full condition). Nonclinical undergraduates were randomly assigned to one of five protocols: Partial-Defusion, Full-Defusion, Partial-Distraction, Full-Distraction, and a distraction-based experimental control task. The Full-Defusion condition reduced the emotional discomfort and believability of negative self-referential thoughts significantly more than other comparison conditions. The positive results of the Full-Defusion condition were also found among participants with elevated depressive symptoms.

Nature of Science Progression in School Year 1-9: a Case Study of Teachers' Suggestions and Rationales

NASA Astrophysics Data System (ADS)

Leden, Lotta; Hansson, Lena

2017-07-01

The inclusion of nature of science (NOS) in science education has for a long time been regarded as crucial. There is, however, a lack of research on appropriate NOS aspects for different educational levels. An even more neglected area of research is that focusing on teachers' perspectives on NOS teaching at different levels. The aim of this article is to examine NOS progression in the light of teachers' suggestions and rationales. In order to obtain teachers' informed perspectives, we chose to involve six teachers (teaching grades 1-9) in a 3-year research project. They took part in focus group discussions about NOS and NOS teaching as well as implemented jointly planned NOS teaching sessions. Data that this article builds on was collected at the end of the project. The teachers' suggestions for NOS progression often relied on adding more NOS issues at every stage, thereby creating the foundations of a broader but not necessarily deeper understanding of NOS. Five rationales, for if/when specific NOS issues are appropriate to introduce, emerged from the analysis of the teacher discussions. Some of these rationales, including practice makes perfect and increasing levels of depth can potentially accommodate room for many NOS issues in the science classroom, while maturity and experience instead has a restricting effect on NOS teaching. Also, choice of context and teaching approaches play an important role in teachers' rationales for whether specific NOS issues should be included or not at different stages. The article discusses the implications for teacher education and professional development.

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology.

PubMed

Cerrato, Enrico; Quirós, Alicia; Echavarría-Pinto, Mauro; Mejia-Renteria, Hernan; Aldazabal, Andres; Ryan, Nicola; Gonzalo, Nieves; Jimenez-Quevedo, Pilar; Nombela-Franco, Luis; Salinas, Pablo; Núñez-Gil, Iván J; Rumoroso, José Ramón; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

2017-05-19

In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).

[Growing up as an occupation child of World War II in Germany: Rationale and methods of a study on German occupation children].

PubMed

Kaiser, Marie; Kuwert, Philipp; Glaesmer, Heide

2015-01-01

To date the experiences of German occupation children (GOC) have been described solely in historical studies; empirical research on the psychosocial consequences growing up as German occupation children was missing. This paper provides an introduction to the background, methodological approaches and descriptive information on a sample for the first German-based empirical study on this topic. It also touches on methodical challenges and solution processes. Children born of war resemble a target group that is difficult to reach (hidden population). Therefore, an investigation needs consultation of both people from the target group and scientific experts (participatory approach) as well as specific methodological approaches. The questionnaire utilized contains adaptations of established and psychometrically validated instruments as well as adapted self-developed items. N = 146 occupation children were surveyed (mean age 63.4, 63.0% women) via press release and contact to platforms of children born of war. Despite methodological challenges an instrument to assess the target group was developed through participatory methods. The instrument shows high relevance for the target group and is highly accepted. High rates of American and French participants show the influence of networking in platforms on successful recruitment.

Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

PubMed

Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

2014-01-01

The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation.

PubMed

Kim, Young Kwan; Kameo, Yoshitaka; Tanaka, Sakae; Adachi, Taiji

2017-10-01

To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.

Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko

Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU andmore » SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC. - Highlights: • Pharmacological inhibition of sphingosine kinase 1/2 augments cytotoxic effects of 5-FU in HepG2 cells. • Co-administration of 5-FU and SKI-II synergistically inhibits cell proliferation, reduces cell migration and clonogenic survival and increases apoptosis induction in HepG2 cells. • The mechanism underlying chemosensitization effects includes attenuation of FAK/IGF-1R and osteopontin signaling leading to the inhibition of NF-κB activity and its downstream targets SIRT1 and p38 MAPK.« less

Large Deployable Reflector Science and Technology Workshop. Volume 2: Scientific Rationale and Technology Requirements

NASA Technical Reports Server (NTRS)

Hollenbach, D. (Editor)

1983-01-01

The scientific rationale for the large deployable reflector (LDR) and the overall technological requirements are discussed. The main scientific objectives include studies of the origins of planets, stars and galaxies, and of the ultimate fate of the universe. The envisioned studies require a telescope with a diameter of at least 20 m, diffraction-limited to wavelengths as short as 30-50 micron. In addition, light-bucket operation with 1 arcsec spatial resolution in the 2-4 microns wavelength region would be useful in studies of high-redshifted galaxies. Such a telescope would provide a large increase in spectroscopic sensitivity and spatial resolving power compared with existing or planned infrared telescopes.

Interns overestimate the effectiveness of their hand-off communication.

PubMed

Chang, Vivian Y; Arora, Vineet M; Lev-Ari, Shiri; D'Arcy, Michael; Keysar, Boaz

2010-03-01

Theories from the psychology of communication may be applicable in understanding why hand-off communication is inherently problematic. The purpose of this study was to assess whether postcall pediatric interns can correctly estimate the patient care information and rationale received by on-call interns during hand-off communication. Pediatric interns at the University of Chicago were interviewed about the hand-off. Postcall interns were asked to predict what on-call interns would report as the important pieces of information communicated during the hand-off about each patient, with accompanying rationale. Postcall interns also guessed on-call interns' rating of how well the hand-offs went. Then, on-call interns were asked to list the most important pieces of information for each patient that postcall interns communicated during the hand-off, with accompanying rationale. On-call interns also rated how well the hand-offs went. Interns had access to written hand-offs during the interviews. We conducted 52 interviews, which constituted 59% of eligible interviews. Seventy-two patients were discussed. The most important piece of information about a patient was not successfully communicated 60% of the time, despite the postcall intern's believing that it was communicated. Postcall and on-call interns did not agree on the rationales provided for 60% of items. In addition, an item was more likely to be effectively communicated when it was a to-do item (65%) or an item related to anticipatory guidance (69%) compared with a knowledge item (38%). Despite the lack of agreement on content and rationale of information communicated during hand-offs, peer ratings of hand-off quality were high. Pediatric interns overestimated the effectiveness of their hand-off communication. Theories from communication psychology suggest that miscommunication is caused by egocentric thought processes and a tendency for the speaker to overestimate the receiver's understanding. This study demonstrates that systematic causes of miscommunication may play a role in hand-off quality.

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.

PubMed

Teismann, Henning; Wersching, Heike; Nagel, Maren; Arolt, Volker; Heindel, Walter; Baune, Bernhard T; Wellmann, Jürgen; Hense, Hans-Werner; Berger, Klaus

2014-06-13

Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.

Planned approaches to business and school partnerships. Does it make a difference? The business perspective.

PubMed

Lee, Kerry; Hope, John; Abdulghani, Fatima

2016-04-01

In many countries, schools are encouraged to link with business to add authenticity to learning. The number of these business-school partnerships has shown a marked increase over the last twenty years. Traditionally researchers investigating these partnerships have focussed on the schools' perspectives (Du, Bhattacharya, & Sen, 2010, pp. 32-33), however this New Zealand research has focused solely on the business perspective of established school partnerships. The study used a mixed methods approach utilising both online survey and semi-structured interviews. Ten out of the forty participating businesses surveyed used a brokering organisation as a way of developing and maintaining these partnerships and some developed rationales to support the partnership. This study investigated the value of using brokering organisations, rationales and designated staff to support business-school partnerships. Findings indicate that brokers and designated staff play a very effective role in enhancing business-school links, and more benefits are perceived when a rationale has been established. It is anticipated that these findings will support the development and success of business-school partnerships. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bergmann's Rule, Adaptation, and Thermoregulation in Arctic Animals: Conflicting Perspectives from Physiology, Evolutionary Biology, and Physical Anthropology After World War II.

PubMed

Hagen, Joel B

2017-05-01

Bergmann's rule and Allen's rule played important roles in mid-twentieth century discussions of adaptation, variation, and geographical distribution. Although inherited from the nineteenth-century natural history tradition these rules gained significance during the consolidation of the modern synthesis as evolutionary theorists focused attention on populations as units of evolution. For systematists, the rules provided a compelling rationale for identifying geographical races or subspecies, a function that was also picked up by some physical anthropologists. More generally, the rules provided strong evidence for adaptation by natural selection. Supporters of the rules tacitly, or often explicitly, assumed that the clines described by the rules reflected adaptations for thermoregulation. This assumption was challenged by the physiologists Laurence Irving and Per Scholander based on their arctic research conducted after World War II. Their critique spurred a controversy played out in a series of articles in Evolution, in Ernst Mayr's Animal Species and Evolution, and in the writings of other prominent evolutionary biologists and physical anthropologists. Considering this episode highlights the complexity and ambiguity of important biological concepts such as adaptation, homeostasis, and self-regulation. It also demonstrates how different disciplinary orientations and styles of scientific research influenced evolutionary explanations, and the consequent difficulties of constructing a truly synthetic evolutionary biology in the decades immediately following World War II.

IL1RN Coding Variant Is Associated with Lower Risk of Acute Respiratory Distress Syndrome and Increased Plasma IL-1 Receptor Antagonist

PubMed Central

Feng, Rui; Li, Mingyao; Zhao, Yang; Sheu, Chau-Chyun; Tejera, Paula; Gallop, Robert; Bellamy, Scarlett; Rushefski, Melanie; Lanken, Paul N.; Aplenc, Richard; O’Keefe, Grant E.; Wurfel, Mark M.; Christiani, David C.; Christie, Jason D.

2013-01-01

Rationale: Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete. Objectives: To identify genetic risk variants for ARDS using large scale genotyping. Methods: A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n = 224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P < 5 × 10−4 for replication in stage II, a trauma case–control population (n = 778). SNPs replicating their association in stage II (P < 0.005) were tested in a stage III nested case–control population of mixed subjects in the intensive care unit (n = 2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels. Measurements and Main Results: A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P < 0.004) and III (P < 0.02), and was robust to clinical adjustment (combined odds ratio = 0.81; P = 4.2 × 10−5). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN. Conclusions: The IL1RN SNP rs315952C is associated with decreased risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk. PMID:23449693

Assessing the reliability and validity of the Chinese Sexual Assault Symptom Scale (C-SASS): scale development and validation.

PubMed

Wang, Chang-Hwai; Lee, Jin-Chuan; Yuan, Yu-Hsi

2014-01-01

The purpose of this research is to establish and verify the psychometric and structural properties of the self-report Chinese Sexual Assault Symptom Scale (C-SASS) to assess the trauma experienced by Chinese victims of sexual assault. An earlier version of the C-SASS was constructed using a modified list of the same trauma symptoms administered to an American sample and used to develop and validate the Sexual Assault Symptom Scale II (SASS II). The rationale of this study is to revise the earlier version of the C-SASS, using a larger and more representative sample and more robust statistical analysis than in earlier research, to permit a more thorough examination of the instrument and further confirm the dimensions of sexual assault trauma in Chinese victims of rape. In this study, a sample of 418 victims from northern Taiwan was collected to confirm the reliability and validity of the C-SASS. Exploratory factor analysis yielded five common factors: Safety Fears, Self-Blame, Health Fears, Anger and Emotional Lability, and Fears About the Criminal Justice System. Further tests of the validity and composite reliability of the C-SASS were provided by the structural equation modeling (SEM). The results indicated that the C-SASS was a brief, valid, and reliable instrument for assessing sexual assault trauma among Chinese victims in Taiwan. The scale can be used to evaluate victims in sexual assault treatment centers around Taiwan, as well as to capture the characteristics of sexual assault trauma among Chinese victims.

STAT3 Mediates Nilotinib Response in KIT-Altered Melanoma: A Phase II Multicenter Trial of the French Skin Cancer Network.

PubMed

Delyon, Julie; Chevret, Sylvie; Jouary, Thomas; Dalac, Sophie; Dalle, Stephane; Guillot, Bernard; Arnault, Jean-Philippe; Avril, Marie-Françoise; Bedane, Christophe; Bens, Guido; Pham-Ledard, Anne; Mansard, Sandrine; Grange, Florent; Machet, Laurent; Meyer, Nicolas; Legoupil, Delphine; Saiag, Philippe; Idir, Zakia; Renault, Victor; Deleuze, Jean-François; Hindie, Elif; Battistella, Maxime; Dumaz, Nicolas; Mourah, Samia; Lebbe, Celeste

2018-01-01

Mutated oncogenic KIT is a therapeutic target in melanoma. We conducted a multicenter phase II trial on the KIT inhibitor nilotinib in patients with unresectable melanoma harboring KIT alteration. The primary endpoint was the response rate (complete response or partial response following Response Evaluation Criteria in Solid Tumors criteria) at 6 months. Pharmacodynamic studies using KIT sequencing, qPCR array, and immunostaining of downstream KIT effectors were performed during treatment. Twenty-five patients were included and received 400 mg oral nilotinib twice daily. At 6 months, nilotinib induced tumor response in four patients. The best overall response rate was 20% and the disease control rate was 56%, limited to patients harboring exon 11 or 13 mutations. Four patients exhibited durable response, including three persisting (3.6 and 2.8 years for two patients with stage IIIC and 2.5 years for one with IVM1b melanoma). A reduction in signal transducer and activator of transcription (STAT) 3 phosphorylation and its effectors (BCL-2, MCL-1) in tumors during follow-up was significantly associated with clinical response. In the KIT-mutated melanoma cell line M230, nilotinib reduced STAT3 signaling and STAT inhibitors were as efficient as KIT inhibitors in reducing cell proliferation. Our study evidences a significant association between STAT3 inhibition and response to nilotinib, and provides a rationale for future research assessing STAT inhibitors in KIT-mutated melanoma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Getting inside acupuncture trials - Exploring intervention theory and rationale

PubMed Central

2011-01-01

Background Acupuncture can be described as a complex intervention. In reports of clinical trials the mechanism of acupuncture (that is, the process by which change is effected) is often left unstated or not known. This is problematic in assisting understanding of how acupuncture might work and in drawing together evidence on the potential benefits of acupuncture. Our aim was to aid the identification of the assumed mechanisms underlying the acupuncture interventions in clinical trials by developing an analytical framework to differentiate two contrasting approaches to acupuncture (traditional acupuncture and Western medical acupuncture). Methods Based on the principles of realist review, an analytical framework to differentiate these two contrasting approaches was developed. In order to see how useful the framework was in uncovering the theoretical rationale, it was applied to a set of trials of acupuncture for fatigue and vasomotor symptoms, identified from a wider literature review of acupuncture and early stage breast cancer. Results When examined for the degree to which a study demonstrated adherence to a theoretical model, two of the fourteen selected studies could be considered TA, five MA, with the remaining seven not fitting into any recognisable model. When examined by symptom, five of the nine vasomotor studies, all from one group of researchers, are arguably in the MA category, and two a TA model; in contrast, none of the five fatigue studies could be classed as either MA or TA and all studies had a weak rationale for the chosen treatment for fatigue. Conclusion Our application of the framework to the selected studies suggests that it is a useful tool to help uncover the therapeutic rationale of acupuncture interventions in clinical trials, for distinguishing between TA and MA approaches and for exploring issues of model validity. English language acupuncture trials frequently fail to report enough detail relating to the intervention. We advocate using this framework to aid reporting, along with further testing and refinement of the framework. PMID:21414187

Structural characterization of a bridged 99Tc-Sn-dimethylglyoxime complex: implications for the chemistry of 99mTc-radiopharmaceuticals prepared by the Sn (II) reduction of pertechnetate.

PubMed Central

Deutsch, E; Elder, R C; Lange, B A; Vaal, M J; Lay, D G

1976-01-01

Reduction of pertechnetate by tin(II) in the presence of dimethylglyoxime is shown, by single crystal x-ray analysis, to yield a technetium-tin-dimethylglyoxime complex in which tin and technetium are intimately connected by a triple bridging arrangement. One bridge consists of a single oxygen atom and it is hypothesized that this bridge arises from the inner sphere reduction of technetium by tin(II), the electrons being transferred through a technetium "yl" oxygen which eventually becomes the bridging atom. Two additional bridges arise from two dimethylglyoxime ligands that function as bidentate nitrogen donors towards Tc and monodentate oxygen donors towards Sn. The tin atom can thus be viewed as providing a three-pronged "cap" on one end of the Tc-dimethylglyoxime complex. The additional coordination sites around Tc are occupied by the two nitrogens of a third dimethylglyoxime ligand, making the Tc seven-coordinate. The additional coordination sites around Sn are occupied by three chloride anions, giving the Sn a fac octahedral coordination environment. From indirect evidence the oxidation states of tin and technetium are tentatively assigned to be IV and V, respectively. Since most 99mTc-radiopharmaceuticals are synthesized by the tin(II) reduction of pertechnetate, it is likely that the Sn-O-Tc linkage described in this work is an important feature of the chemistry of these species. This linkage also provides a ready rationale for the close association of tin and technetium observed in many 99mTc-radiopharmaceuticals. PMID:1069984

Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II–Induced Hypertension

PubMed Central

Xiao, Liang; Kirabo, Annet; Wu, Jing; Saleh, Mohamed A.; Zhu, Linjue; Wang, Feng; Takahashi, Takamune; Loperena, Roxana; Foss, Jason D.; Mernaugh, Raymond L.; Chen, Wei; Roberts, Jackson; Osborn, John W.; Itani, Hana A.; Harrison, David G.

2015-01-01

Rationale Inflammation and adaptive immunity plays a crucial role in the development of hypertension. Angiotensin II and likely other hypertensive stimuli activate the central nervous system and promote T cell activation and end-organ damage in peripheral tissues. Objective To determine if renal sympathetic nerves mediate renal inflammation and T cell activation in hypertension. Methods and Results Bilateral renal denervation (RDN) using phenol application to the renal arteries reduced renal norepinephrine (NE) levels and blunted angiotensin II induced hypertension. Bilateral RDN also reduced inflammation, as reflected by decreased accumulation of total leukocytes, T cells and both CD4+ and CD8+ T cells in the kidney. This was associated with a marked reduction in renal fibrosis, albuminuria and nephrinuria. Unilateral RDN, which partly attenuated blood pressure, only reduced inflammation in the denervated kidney, suggesting that this effect is pressure independent. Angiotensin II also increased immunogenic isoketal-protein adducts in renal dendritic cells (DCs) and increased surface expression of costimulation markers and production of IL-1α, IL-1β, and IL-6 from splenic dendritic cells. NE also dose dependently stimulated isoketal formation in cultured DCs. Adoptive transfer of splenic DCs from angiotensin II-treated mice primed T cell activation and hypertension in recipient mice. RDN prevented these effects of hypertension on DCs. In contrast to these beneficial effects of ablating all renal nerves, renal afferent disruption with capsaicin had no effect on blood pressure or renal inflammation. Conclusions Renal sympathetic nerves contribute to dendritic cell activation, subsequent T cell infiltration and end-organ damage in the kidney in the development of hypertension. PMID:26156232

The Role of Glia in Stress: Polyamines and Brain Disorders

PubMed Central

Skatchkov, Serguei; Woodbury, Michel; Eaton, Misty

2014-01-01

Synopsis This review focuses on the roles of glia and polyamines (PAs) in brain function and dysfunction, highlighting how PAs are one of the principal differences between glia and neurons as they are surprisingly stored, but not synthesized, almost exclusively in glial cells from which they can be released to regulate neuronal synaptic activity. The review includes the novel role of PAs, such as putrescine (PUT), spermidine (SPD) and spermine (SPM) and their precursors and derivatives. However: (i) PAs have not yet been a focus of much glial research; (ii) PAs affect many neuronal and glial receptors, channels and transporters; (iii) PAs are therefore key elements in the development of many diseases and syndromes (iv) thus forming the rationale for PA and glia focused therapy for these conditions. PMID:25455070

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

PubMed Central

Conrad, Kirk P.

2016-01-01

BACKGROUND Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand–receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1α) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR-γ) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non-pregnant condition and during pregnancy. WIDER IMPLICATIONS There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a ‘pregnancy’ hormone, is likely to prove salutary for several disease indications in the non-pregnant population. PMID:27385360

Constructing a Theory- and Evidence-Based Treatment Rationale for Complex eHealth Interventions: Development of an Online Alcohol Intervention Using an Intervention Mapping Approach.

PubMed

Brendryen, Håvar; Johansen, Ayna; Nesvåg, Sverre; Kok, Gerjo; Duckert, Fanny

2013-01-23

Due to limited reporting of intervention rationale, little is known about what distinguishes a good intervention from a poor one. To support improved design, there is a need for comprehensive reports on novel and complex theory-based interventions. Specifically, the emerging trend of just-in-time tailoring of content in response to change in target behavior or emotional state is promising. The objective of this study was to give a systematic and comprehensive description of the treatment rationale of an online alcohol intervention called Balance. We used the intervention mapping protocol to describe the treatment rationale of Balance. The intervention targets at-risk drinking, and it is delivered by email, mobile phone text messaging, and tailored interactive webpages combining text, pictures, and prerecorded audio. The rationale of the current treatment was derived from a self-regulation perspective, and the overarching idea was to support continued self-regulation throughout the behavior change process. Maintaining the change efforts over time and coping adaptively during critical moments (eg, immediately before and after a lapse) are key factors to successful behavior change. Important elements of the treatment rationale to achieving these elements were: (1) emotion regulation as an inoculation strategy against self-regulation failure, (2) avoiding lapses by adaptive coping, and (3) avoiding relapse by resuming the change efforts after a lapse. Two distinct and complementary delivery strategies were used, including a day-to-day tunnel approach in combination with just-in-time therapy. The tunnel strategy was in accordance with the need for continuous self-regulation and it functions as a platform from which just-in-time therapy was launched. Just-in-time therapy was used to support coping during critical moments, and started when the client reports either low self-efficacy or that they were drinking above target levels. The descriptions of the treatment rationale for Balance, the alcohol intervention reported herein, provides an intervention blueprint that will aid in interpreting the results from future program evaluations. It will ease comparisons of program rationales across interventions, and may assist intervention development. By putting just-in-time therapy within a complete theoretical and practical context, including the tunnel delivery strategy and the self-regulation perspective, we have contributed to an understanding of how multiple delivery strategies in eHealth interventions can be combined. Additionally, this is a call for action to improve the reporting practices within eHealth research. Possible ways to achieve such improvement include using a systematic and structured approach, and for intervention reports to be published after peer-review and separately from evaluation reports.

Constructing a Theory- and Evidence-Based Treatment Rationale for Complex eHealth Interventions: Development of an Online Alcohol Intervention Using an Intervention Mapping Approach

PubMed Central

Johansen, Ayna; Nesvåg, Sverre; Kok, Gerjo; Duckert, Fanny

2013-01-01

Background Due to limited reporting of intervention rationale, little is known about what distinguishes a good intervention from a poor one. To support improved design, there is a need for comprehensive reports on novel and complex theory-based interventions. Specifically, the emerging trend of just-in-time tailoring of content in response to change in target behavior or emotional state is promising. Objective The objective of this study was to give a systematic and comprehensive description of the treatment rationale of an online alcohol intervention called Balance. Methods We used the intervention mapping protocol to describe the treatment rationale of Balance. The intervention targets at-risk drinking, and it is delivered by email, mobile phone text messaging, and tailored interactive webpages combining text, pictures, and prerecorded audio. Results The rationale of the current treatment was derived from a self-regulation perspective, and the overarching idea was to support continued self-regulation throughout the behavior change process. Maintaining the change efforts over time and coping adaptively during critical moments (eg, immediately before and after a lapse) are key factors to successful behavior change. Important elements of the treatment rationale to achieving these elements were: (1) emotion regulation as an inoculation strategy against self-regulation failure, (2) avoiding lapses by adaptive coping, and (3) avoiding relapse by resuming the change efforts after a lapse. Two distinct and complementary delivery strategies were used, including a day-to-day tunnel approach in combination with just-in-time therapy. The tunnel strategy was in accordance with the need for continuous self-regulation and it functions as a platform from which just-in-time therapy was launched. Just-in-time therapy was used to support coping during critical moments, and started when the client reports either low self-efficacy or that they were drinking above target levels. Conclusions The descriptions of the treatment rationale for Balance, the alcohol intervention reported herein, provides an intervention blueprint that will aid in interpreting the results from future program evaluations. It will ease comparisons of program rationales across interventions, and may assist intervention development. By putting just-in-time therapy within a complete theoretical and practical context, including the tunnel delivery strategy and the self-regulation perspective, we have contributed to an understanding of how multiple delivery strategies in eHealth interventions can be combined. Additionally, this is a call for action to improve the reporting practices within eHealth research. Possible ways to achieve such improvement include using a systematic and structured approach, and for intervention reports to be published after peer-review and separately from evaluation reports. PMID:23612478

Rationales for the Lightning Launch Commit Criteria

NASA Technical Reports Server (NTRS)

Willett, John C. (Editor); Merceret, Francis J. (Editor); Krider, E. Philip; O'Brien, T. Paul; Dye, James E.; Walterscheid, Richard L.; Stolzenburg, Maribeth; Cummins, Kenneth; Christian, Hugh J.; Madura, John T.

2016-01-01

Since natural and triggered lightning are demonstrated hazards to launch vehicles, payloads, and spacecraft, NASA and the Department of Defense (DoD) follow the Lightning Launch Commit Criteria (LLCC) for launches from Federal Ranges. The LLCC were developed to prevent future instances of a rocket intercepting natural lightning or triggering a lightning flash during launch from a Federal Range. NASA and DoD utilize the Lightning Advisory Panel (LAP) to establish and develop robust rationale from which the criteria originate. The rationale document also contains appendices that provide additional scientific background, including detailed descriptions of the theory and observations behind the rationales. The LLCC in whole or part are used across the globe due to the rigor of the documented criteria and associated rationale. The Federal Aviation Administration (FAA) adopted the LLCC in 2006 for commercial space transportation and the criteria were codified in the FAA's Code of Federal Regulations (CFR) for Safety of an Expendable Launch Vehicle (Appendix G to 14 CFR Part 417, (G417)) and renamed Lightning Flight Commit Criteria in G417.

Apoptotic impact on Brugia malayi by sulphonamido-quinoxaline: search for a novel therapeutic rationale.

PubMed

Bhoj, Priyanka S; Ingle, Rahul G; Goswami, Kalyan; Jena, Lingaraj; Wadher, Shailesh

2018-05-01

Human lymphatic filariasis although not fatal but poses serious socioeconomic burden due to associated disability. This is reflected by the huge magnitude of the estimated disability-adjusted life years of about 5.09 million. Therefore, following WHO mandate, our earlier studies on antifilarial drug development revealed the significance of apoptosis. Apoptotic impact has been implicated in anticancer rationale of several drugs. In this study, we explored the antifilarial potential of sulphonamido-quinoxaline compounds, shown to be specific inhibitor for c-Met kinase in human cancer cells. Out of studied compounds, Q4, showing favorable drug-likeness and medicinal chemistry properties on bioinformatics platform along with subsequently recorded lowest IC 100 value, was considered as a suitable antifilarial candidate. Significant apoptosis due to mitochondrial involvement was recorded in drug-treated parasite unlike untreated control. In spite of homology between human c-Met kinase and Brugia malayi counterpart, comparative docking result of this compound showed more favorable binding parameters with the parasitic target. The wide gap between IC 100 and LD 50 values further confirmed the therapeutic safety. We propose sulphonamido-quinoxaline derivative as a lead candidate for antifilarial drug development. Further study is warranted to authenticate parasitic c-Met kinase as a novel therapeutic target reminiscent of anticancer rationale implicating inhibition of proliferation.

What is the biochemical and physiological rationale for using cold-water immersion in sports recovery? A systematic review.

PubMed

Bleakley, Chris M; Davison, Gareth W

2010-02-01

Cold-water immersion (CWI) is a popular recovery intervention after exercise. The scientific rationale is not clear, and there are no clear guidelines for its use. The aim of this review was to study the physiological and biochemical effect of short periods of CWI. A computer-based literature search, citation tracking and related articles searches were undertaken. Primary research studies using healthy human participants, immersed in cold water (<15 degrees C), for 5 min durations or less were included. Data were extracted on body temperature, cardiovascular, respiratory and biochemical response. 16 studies were included. Sample size was restricted, and there was a large degree of study heterogeneity. CWI was associated with an increase in heart rate, blood pressure, respiratory minute volume and metabolism. Decreases in end tidal carbon dioxide partial pressure and a decrease in cerebral blood flow were also reported. There was evidence of increases in peripheral catecholamine concentration, oxidative stress and a possible increase in free-radical-species formation. The magnitude of these responses may be attenuated with acclimatisation. CWI induces significant physiological and biochemical changes to the body. Much of this evidence is derived from full body immersions using resting healthy participants. The physiological and biochemical rationale for using short periods of CWI in sports recovery still remains unclear.

Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial.

PubMed

Bolli, Roberto; Hare, Joshua M; Henry, Timothy D; Lenneman, Carrie G; March, Keith L; Miller, Kathy; Pepine, Carl J; Perin, Emerson C; Traverse, Jay H; Willerson, James T; Yang, Phillip C; Gee, Adrian P; Lima, João A; Moyé, Lem; Vojvodic, Rachel W; Sayre, Shelly L; Bettencourt, Judy; Cohen, Michelle; Ebert, Ray F; Simari, Robert D

2018-07-01

SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome. Copyright © 2018. Published by Elsevier Inc.

Theoretical rationale for music selection in oncology intervention research: an integrative review.

PubMed

Burns, Debra S

2012-01-01

Music-based interventions have helped patients with cancer improve their quality of life, decrease treatment related distress, and manage pain. However, quantitative findings from music intervention studies are inconsistent. The purpose of this review was to explore the theoretical underpinnings for the selection of the music stimuli used to influence targeted outcomes. It was hypothesized that disparate findings were due in part to the atheoretical nature of music selection and the resulting diversity in music stimuli between and within studies. A systematic research synthesis including a comprehensive database and reference list search resulted in 22 studies. Included studies were compiled into two tables cataloging intervention theory, intervention content, and outcomes. A majority of studies did not provide a rationale or intervention theory for the delivery of music or choice of outcomes. Recorded music was the most common delivery method, but the specific music was rarely included within the report. Only two studies that included a theoretical framework reported null results on at least some of the outcomes. Null results are partially explained by an incomplete or mismatch in intervention theory and music selection and delivery. While the inclusion of an intervention theory does not guarantee positive results, including a theoretical rationale for the use of music, particular therapeutic processes or mechanisms, and the specifics of how music is selected and delivered increases scientific rigor and the probability of clinical translation.

Real-time monitoring of genetically modified Chlamydomonas reinhardtii during the Foton M3 space mission and ground irradiation experiment

NASA Astrophysics Data System (ADS)

Lambreva, Maya; Rea, Giuseppina; Antonacci, Amina; Serafini, Agnese; Damasso, Mario; Margonelli, Andrea; Johanningmeier, Udo; Bertalan, Ivo; Pezzotti, Gianni; Giardi, Maria Teresa

Long-term space exploration, colonization or habitation requires biological life support systems capable to cope with the deleterious space environment. The use of oxygenic photosynthetic microrganisms is an intriguing possibility mainly for food, O2 and nutraceutical compounds production. The critical points of utilizing plantsor algae-based life support systems are the microgravity and the ionizing radiation, which can influence the performance of these organisms. The aim of the present study was to assess the effects of space environment on the photosynthetic activity of various microrganisms and to select space stress-tolerant strains. Site-directed and random mutants of the unicellular green alga Chlamydomonas reinhardtii of Photosystem II D1 protein were used as a model system to test and select the amino acid substitutions capable to account for space stress tolerance. We focussed our studies also on the accumulation of the Photosystem II photoprotective carotenoids (the xantophylls violaxanthin, anteraxanthin and zeaxanthin), powerful antioxidants that epidemiological studies demonstrated to be human vision protectors. Metabolite profiling by quantitative HPLC methods revealed the organisms and the stress conditions capable to accumulate the highest pigment levels. In order to develop a project for a rationale metabolic engineering of algal secondary metabolites overproduction, we are performing expression analyses on the carotenoid biosynthetic pathway under physiological and mimicked space conditions. To identify the consequences of the space environment on the photosynthetic apparatus the changes in the Photosystem II efficiency were monitored in real time during the ESA-Russian Foton-M3 mission in September 2007. For the space flight a high-tech, multicell fluorescence biosensor, Photo-II, was designed and built by the Centre for Advanced Research in Space Optics in collaboration with Kayser-Italy, Biosensor and DAS. Photo-II is an automatic device developed to measure the chlorophyll fluorescence and to provide a living conditions for 24 different algae strains. Twelve different C. reinhardtii strains were analytically selected and two replications for each strain were brought to space, among them, some mutants modified at the level of enzymes involved in the biosynthesis of xanthophylls. We analysed the hourly changes and the daily light/dark trend in the maximum quantum yield of PSII photochemistry as well as some physiological parameters that characterize the post-flight effect on algae viability and photosynthetic performance. The ground control experiments were performed following the same protocol for the sample preparation and the temperature recorded during the pre-flight, flight and post-flight phases. The space flight results in comparison to the ground simulations are discussed.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

PubMed Central

Agréus, Lars; Kuipers, Ernst J; Kupcinskas, Limas; Malfertheiner, Peter; Di Mario, Francesco; Leja, Marcis; Mahachai, Varocha; Yaron, Niv; Van Oijen, Martijn; Perez, Guillermo Perez; Rugge, Massimo; Ronkainen, Jukka; Salaspuro, Mikko; Sipponen, Pentti; Sugano, Kentaro; Sung, Joseph

2012-01-01

Background and aims Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach. PMID:22242613

Rationale, design and methodology of a trial evaluating three strategies designed to improve sedation quality in intensive care units (DESIST study).

PubMed

Walsh, Timothy S; Kydonaki, Kalliopi; Antonelli, Jean; Stephen, Jacqueline; Lee, Robert J; Everingham, Kirsty; Hanley, Janet; Uutelo, Kimmo; Peltola, Petra; Weir, Christopher J

2016-03-04

To describe the rationale, design and methodology for a trial of three novel interventions developed to improve sedation-analgesia quality in adult intensive care units (ICUs). 8 clusters, each a Scottish ICU. All mechanically ventilated sedated patients were potentially eligible for inclusion in data analysis. Cluster randomised design in 8 ICUs, with ICUs randomised after 45 weeks baseline data collection to implement one of four intervention combinations: a web-based educational programme (2 ICUs); education plus regular sedation quality feedback using process control charts (2 ICUs); education plus a novel sedation monitoring technology (2 ICUs); or all three interventions. ICUs measured sedation-analgesia quality, relevant drug use and clinical outcomes, during a 45-week preintervention and 45-week postintervention period separated by an 8-week implementation period. The intended sample size was >100 patients per site per study period. The primary outcome was the proportion of 12 h care periods with optimum sedation-analgesia, defined as the absence of agitation, unnecessary deep sedation, poor relaxation and poor ventilator synchronisation. Secondary outcomes were proportions of care periods with each of these four components of optimum sedation and rates of sedation-related adverse events. Sedative and analgesic drug use, and ICU and hospital outcomes were also measured. Multilevel generalised linear regression mixed models will explore the effects of each intervention taking clustering into account, and adjusting for age, gender and APACHE II score. Sedation-analgesia quality outcomes will be explored at ICU level and individual patient level. A process evaluation using mixed methods including quantitative description of intervention implementation, focus groups and direct observation will provide explanatory information regarding any effects observed. The DESIST study uses a novel design to provide system-level evaluation of three contrasting complex interventions on sedation-analgesia quality. Recruitment is complete and analysis ongoing. NCT01634451. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

PubMed

Gatell, J M

1998-01-01

In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a relatively low baseline viral load. Furthermore, components of these protease inhibitor-sparing combinations such as didanosine or nevirapine are suitable for once daily administration.

Photosynthetic dioxygen formation studied by time-resolved delayed fluorescence measurements--method, rationale, and results on the activation energy of dioxygen formation.

PubMed

Buchta, Joachim; Grabolle, Markus; Dau, Holger

2007-06-01

The analysis of the time-resolved delayed fluorescence (DF) measurements represents an important tool to study quantitatively light-induced electron transfer as well as associated processes, e.g. proton movements, at the donor side of photosystem II (PSII). This method can provide, inter alia, insights in the functionally important inner-protein proton movements, which are hardly detectable by conventional spectroscopic approaches. The underlying rationale and experimental details of the method are described. The delayed emission of chlorophyll fluorescence of highly active PSII membrane particles was measured in the time domain from 10 mus to 60 ms after each flash of a train of nanosecond laser pulses. Focusing on the oxygen-formation step induced by the third flash, we find that the recently reported formation of an S4-intermediate prior to the onset of O-O bond formation [M. Haumann, P. Liebisch, C. Müller, M. Barra, M. Grabolle, H. Dau, Science 310, 1019-1021, 2006] is a multiphasic process, as anticipated for proton movements from the manganese complex of PSII to the aqueous bulk phase. The S4-formation involves three or more likely sequential steps; a tri-exponential fit yields time constants of 14, 65, and 200 mus (at 20 degrees C, pH 6.4). We determine that S4-formation is characterized by a sizable difference in Gibbs free energy of more than 90 meV (20 degrees C, pH 6.4). In the second part of the study, the temperature dependence (-2.7 to 27.5 degrees C) of the rate constant of dioxygen formation (600/s at 20 degrees C) was investigated by analysis of DF transients. If the activation energy is assumed to be temperature-independent, a value of 230 meV is determined. There are weak indications for a biphasicity in the Arrhenius plot, but clear-cut evidence for a temperature-dependent switch between two activation energies, which would point to the existence of two distinct rate-limiting steps, is not obtained.

Resistance to aspirin and thienopyridines in diabetes mellitus and metabolic syndrome.

PubMed

Anfossi, Giovanni; Russo, Isabella; Trovati, Mariella

2008-10-01

Platelets from patients affected by diabetes mellitus and metabolic syndrome show an impaired sensitivity to physiological antiaggregating agents and an enhanced activation state, mirrored by an increased expression of membrane activation markers; furthermore, they are more prone to form spontaneous microaggregates with ADP receptor involvement. These abnormalities are responsible for a pro-thrombotic condition, contributing to a high cardiovascular risk. This pattern of platelet abnormalities provides a strong rationale for aggressive antiplatelet therapy strongly recommended by guidelines both in diabetes mellitus and in metabolic syndrome, not only in the setting of acute coronary syndromes, but also for the long-term prevention of the cardiovascular events. Antiplatelet therapy in these pathological conditions, however, is still a matter of intense debate, especially because a high prevalence of "resistance" to these drugs (and to aspirin in particular) has been described in these patients. This may result in non-significant reductions in cardiovascular events. Different factors seem to be involved, including: i) genetic polymorphisms; ii) hyperglycemia and poor metabolic control; iii) reduced sensitivity to nitric oxide; iv) a pro-inflammatory and/or pro-thrombotic status, and, v) increased oxidative stress. This review will take into consideration: i) the results of the most relevant studies addressing the effects of the anti-aggregating treatment in patients affected by diabetes mellitus and/or metabolic syndrome, and, ii) the biochemical mechanisms accounting for the impaired sensitivity to aspirin and thienopyridines in the above mentioned clinical conditions.

An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma

PubMed Central

Kim, George P.; Mahoney, Michelle R.; Szydlo, Daniel; Mok, Tony S. K.; Marshke, Robert; Holen, Kyle; Picus, Joel; Boyer, Michael; Pitot, Henry C.; Rubin, Joseph; Philip, Philip A.; Nowak, Anna; Wright, John J.; Erlichman, Charles

2013-01-01

Summary Background and Rationale Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitinproteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. Methods The primary endpoint was confirmed tumor response rate (RR) with secondary endpoints including duration of response, time to disease progression, survival and toxicity. Treatment consisted of bortezomib, 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of each 21-day treatment cycle. Eligibility included: no prior systemic chemotherapy, ECOG PS 0-2, Child-Pugh A or B, preserved hematologic, hepatic and neurologic function; prior liver-directed therapy was permitted. Results Thirty-five patients enrolled and received a median of 2 cycles of treatment (range 1–12). Overall, 24 and 4 patients had a maximum severity of grade 3 and 4 adverse events (AEs), respectively. No treatment related deaths occurred. Only thrombocytopenia (11%) was seen in greater than 10% of patients. One patient achieved a partial response, lasting 13 weeks during treatment and progressed 11.6 months later; two patients received treatment for greater than 6 months. Median time-to-progression was 1.6 months and median survival was 6.0 months. Conclusions This international, multicenter trial evaluated bortezomib as monotherapy in unresectable HCC patients. And, despite the lack of significant activity, this report serves as a baseline clinical experience for the development of future dual biologic approaches including bortezomib. PMID:20839030

Rationale and Methods of the Substance Use and Psychological Injury Combat Study (SUPIC): A Longitudinal Study of Army Service Members Returning from Deployment in FY2008–2011

PubMed Central

Larson, Mary Jo; Adams, Rachel Sayko; Mohr, Beth A.; Harris, Alex H. S.; Merrick, Elizabeth L.; Funk, Wendy; Hofmann, Keith; Wooten, Nikki R.; Jeffery, Diana D.; Williams, Thomas V.

2013-01-01

SUPIC will examine whether early detection and intervention for post-deployment problems among Army Active Duty and National Guard/Reservists returning from Iraq or Afghanistan are associated with improved long-term substance use and psychological outcomes. This paper describes the rationale and significance of SUPIC, and presents demographic and deployment characteristics of the study sample (N=643,205), and self-reported alcohol use and health problems from the subsample with matched post-deployment health assessments (N=487,600). This longitudinal study aims to provide new insight into the long-term post-deployment outcomes of Army members by combining service member data from the Military Health System and Veterans Health Administration. PMID:23869459

Picking Up Artifacts: Storyboarding as a Gateway to Reuse

NASA Astrophysics Data System (ADS)

Wahid, Shahtab; Branham, Stacy M.; Cairco, Lauren; McCrickard, D. Scott; Harrison, Steve

Storyboarding offers designers the opportunity to illustrate a visual narrative of use. Because designers often refer to past ideas, we argue storyboards can be constructed by reusing shared artifacts. We present a study in which we explore how designers reuse artifacts consisting of images and rationale during storyboard construction. We find images can aid in accessing rationale and that connections among features aid in deciding what to reuse, creating new artifacts, and constructing. Based on requirements derived from our findings, we present a storyboarding tool, PIC-UP, to facilitate artifact sharing and reuse and evaluate its use in an exploratory study. We conclude with remarks on facilitating reuse and future work.

A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).

PubMed

Kataoka, Kozo; Tsushima, Takahiro; Mizusawa, Junki; Hironaka, Shuichi; Tsubosa, Yasuhiro; Kii, Takayuki; Shibuya, Yuichi; Chin, Keisho; Katayama, Hiroshi; Kato, Ken; Fukuda, Haruhiko; Kitagawa, Yuko

2015-05-01

Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Design of the heart failure endpoint evaluation of AII-antagonist losartan (HEAAL) study in patients intolerant to ACE-inhibitor.

PubMed

Konstam, Marvin A; Poole-Wilson, Philip A; Dickstein, Kenneth; Drexler, Helmut; Justice, Steven J; Komajda, Michel; Malbecq, William; Martinez, Felipe A; Neaton, James D; Riegger, Gunter A J; Guptha, Soneil

2008-09-01

In patients with heart failure and reduced left ventricular ejection fraction, angiotensin receptor blockers have been found to reduce mortality and morbidity and to prevent or reverse left ventricular remodelling, compared to optimized background treatment. In light of these data, The Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL) study was developed to determine whether losartan 150 mg is superior to losartan 50 mg (antihypertensive dose) in reducing morbidity and mortality among patients with symptomatic heart failure who are intolerant of angiotensin-converting enzyme (ACE)-inhibitors. To compare the effect of high and moderate doses of losartan on the primary endpoint of all-cause mortality and hospitalisation due to heart failure in patients (n = 3834) with symptomatic heart failure and an ejection fraction < or = 40% who are intolerant of ACE-inhibitor treatment. This paper presents the rationale, trial design, and baseline characteristics of the study population. The study, which completed recruitment on 31 March 2005, is event-driven and is estimated to accrue the target of 1710 adjudicated primary events during the latter half of 2008. The results of HEAAL should facilitate selection of an optimal dosing regimen for losartan in patients with symptomatic heart failure who are intolerant of ACE-inhibitors.

Evaluating web-based cognitive-affective remediation in recent trauma survivors: study rationale and protocol.

PubMed

Fine, Naomi B; Achituv, Michal; Etkin, Amit; Merin, Ofer; Shalev, Arieh Y

2018-01-01

Background : The immediate aftermath of traumatic events is a period of enhanced neural plasticity, following which some survivors remain with post-traumatic stress disorder (PTSD) whereas others recover. Evidence points to impairments in emotional reactivity, emotion regulation, and broader executive functions as critically contributing to PTSD. Emerging evidence further suggests that the neural mechanisms underlying these functions remain plastic in adulthood and that targeted retraining of these systems may enhance their efficiency and could reduce the likelihood of developing PTSD. Administering targeted neurocognitive training shortly after trauma exposure is a daunting challenge. This work describes a study design addressing that challenge. The study evaluated the direct effects of cognitive remediation training on neurocognitive mechanisms that hypothetically underlay PTSD, and the indirect effect of this intervention on emerging PTSD symptoms. Method : We describe a study rationale, design, and methodological choices involving: (a) participants' enrolment; (b) implementation and management of a daily self-administered, web-based intervention; (c) reliable, timely screening and assessment of treatment of eligible survivors; and (d) defining control conditions and outcome measures. We outline the rationale of choices made regarding study sample, timing of intervention, measurements, monitoring participants' adherence, and ways to harmonize and retain interviewers' fidelity and mitigate eventual burnout by repeated contacts with recently traumatized survivors. Conclusion : Early web-based interventions targeting causative mechanisms of PTSD can be informed by the model presented in this paper.

The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease☆

PubMed Central

Dale, Philippa R; Cernecka, Hana; Schmidt, Martina; Dowling, Mark R; Charlton, Steven J; Pieper, Michael P; Michel, Martin C

2014-01-01

Muscarinic receptor antagonists and β-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and β-adrenoceptors are physiological antagonists for smooth muscle tone in airways and bladder. Muscarinic agonism may attenuate β-adrenoceptor-mediated relaxation more than other contractile stimuli. Chronic treatment with one drug class may regulate expression of the target receptor but also that of the opposing receptor. Prejunctional β2-adrenoceptors can enhance neuronal acetylcholine release. Moreover, at least in the airways, muscarinic receptors and β-adrenoceptors are expressed in different locations, indicating that only a combined modulation of both systems may cause dilatation along the entire bronchial tree. While all of these factors contribute to a rationale for a combination of muscarinic receptor antagonists and β-adrenoceptor agonists, the full value of such combination as compared to monotherapy can only be determined in clinical studies. PMID:24682092

Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status.

PubMed

Swart, Tara; Hurley, Michael J

2016-12-01

Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated Ca V 1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease. Dihydropyridines have been safely used for decades to treat hypertension and other cardiovascular disorders. A phase II clinical trial found that isradipine was safely tolerated by patients with Parkinson's disease, and a phase III trial is currently underway to determine whether treatment with isradipine is neuroprotective and therefore able to slow the progression of Parkinson's disease. This manuscript reviews the current information about the use of dihydropyridines as therapy for Parkinson's disease and discusses the possible mechanism of action of these drugs, highlighting Ca V 1.3 calcium channels as a potential therapeutic target for neuroprotection in Parkinson's disease.

Emerging monoclonal antibodies against Clostridium difficile infection.

PubMed

Péchiné, Séverine; Janoir, Claire; Collignon, Anne

2017-04-01

Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. Areas covered: Herein, the authors review the different assays performed with monoclonal antibodies against C. difficile toxins and surface proteins to treat or prevent primary or recurrent episodes of C. difficile infection in animal models and in clinical trials as well. Notably, the authors lay emphasis on the phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency. They also review new strategies for producing single domain antibodies and nanobodies against C. difficile and new approaches to deliver them in the digestive tract. Expert opinion: Only two human Mabs against TcdA and TcdB have been tested alone or in combination in clinical trials. However, many animal model studies have provided rationale for the use of Mabs and nanobodies in C. difficile infection and pave the way for further clinical investigation.

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

PubMed Central

Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID:26858719

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

PubMed

Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

Overview of experiment design and comparison of models participating in phase 1 of the SPARC Quasi-Biennial Oscillation initiative (QBOi)

NASA Astrophysics Data System (ADS)

Butchart, Neal; Anstey, James A.; Hamilton, Kevin; Osprey, Scott; McLandress, Charles; Bushell, Andrew C.; Kawatani, Yoshio; Kim, Young-Ha; Lott, Francois; Scinocca, John; Stockdale, Timothy N.; Andrews, Martin; Bellprat, Omar; Braesicke, Peter; Cagnazzo, Chiara; Chen, Chih-Chieh; Chun, Hye-Yeong; Dobrynin, Mikhail; Garcia, Rolando R.; Garcia-Serrano, Javier; Gray, Lesley J.; Holt, Laura; Kerzenmacher, Tobias; Naoe, Hiroaki; Pohlmann, Holger; Richter, Jadwiga H.; Scaife, Adam A.; Schenzinger, Verena; Serva, Federico; Versick, Stefan; Watanabe, Shingo; Yoshida, Kohei; Yukimoto, Seiji

2018-03-01

The Stratosphere-troposphere Processes And their Role in Climate (SPARC) Quasi-Biennial Oscillation initiative (QBOi) aims to improve the fidelity of tropical stratospheric variability in general circulation and Earth system models by conducting coordinated numerical experiments and analysis. In the equatorial stratosphere, the QBO is the most conspicuous mode of variability. Five coordinated experiments have therefore been designed to (i) evaluate and compare the verisimilitude of modelled QBOs under present-day conditions, (ii) identify robustness (or alternatively the spread and uncertainty) in the simulated QBO response to commonly imposed changes in model climate forcings (e.g. a doubling of CO2 amounts), and (iii) examine model dependence of QBO predictability. This paper documents these experiments and the recommended output diagnostics. The rationale behind the experimental design and choice of diagnostics is presented. To facilitate scientific interpretation of the results in other planned QBOi studies, consistent descriptions of the models performing each experiment set are given, with those aspects particularly relevant for simulating the QBO tabulated for easy comparison.

Pharmacological modulation of platelet function in hypertension.

PubMed

Blann, Andrew D; Nadar, Sunil; Lip, Gregory Y H

2003-07-01

Platelets exert a considerable influence on human morbidity and mortality. The rationale for their study in hypertension follows the observation that the major consequences of hypertension are stroke and myocardial infarction. However, the etiology of these consequences in hypertension is, paradoxically, not hemorrhagic (as might be expected from the effects of high blood pressure), but occlusive, with thrombus being the culprit lesion. Mechanisms of platelet activation include high shear force, activation of the renin-angiotensin system, endothelial changes, and the presence of comorbidity, such as atrial fibrillation. The treatment of high blood pressure brings about a reversal of the changes seen in the cell. This could be in part due to the direct effect of the drug on the megakaryocyte and/or the platelets themselves, or it might simply be due to the reduction in blood pressure. Some drugs, such as calcium channel antagonists and angiotensin II receptor blockers, however, might have direct effects on platelet biochemistry other than reducing blood pressure. Finally, antiplatelet drugs are becoming an important part of the management of high-risk hypertensives, which aim to minimize vascular complications.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data

PubMed Central

Giles, Thomas D.; Cockcroft, John R.; Pitt, Bertram; Jakate, Abhijeet; Wright, Harold M.

2017-01-01

To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin–angiotensin–aldosterone system inhibitors, when combined, have been deemed ‘less effective’ based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg – a vasodilatory β1-selective antagonist/β3 agonist – and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I–II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension. PMID:28509722

Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

PubMed Central

FRIEDMANN, PETER D.; KATZ, ELIZABETH C.; RHODES, ANNE G.; TAXMAN, FAYE S.; O'CONNELL, DANIEL J.; FRISMAN, LINDA K.; BURDON, WILLIAM M.; FLETCHER, BENNETT W.; LITT, MARK D.; CLARKE, JENNIFER; MARTIN, STEVEN S.

2009-01-01

This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment counselors to provide role induction counseling, contract for pro-social behavior, and deliver contingent reinforcement of behaviors consistent with treatment objectives. The Step'n Out study will randomize 450 drug-involved parolees to collaborative behavioral management or usual parole. Follow-up at 3-and 9-months will assess primary outcomes of rearrest, crime and drug use. If collaborative behavioral management is effective, its wider adoption could improve the outcomes of community reentry of drug-involved ex-offenders. PMID:19809591

Patient perspectives on engagement in shared decision-making for asthma care.

PubMed

Tapp, Hazel; Derkowski, Diane; Calvert, Melissa; Welch, Madelyn; Spencer, Sara

2017-06-01

Engagement of patient and advocacy group stakeholders is increasingly considered essential to meaningful outcomes research. Patient-centred research benefits from partnership formation between patients, clinicians and research team members. Here, we describe the rationale for engaging patients on a research team and a case study of patient engagement on an asthma shared decision-making study. Here, we describe a case study of patient engagement in outcomes research and examine the variety of roles patients are engaged in and the associated impact on the study. Patients assisted the project at various levels and were integrated into the research team by (i) advising on study development; (ii) assisting with design and usability of study materials, including the toolkit, patient surveys and dissemination strategies; and (iii) advocacy via membership in external disease-specific organizations and participating in outcomes research conferences. Patients were engaged both individually and as members of a patient advisory board. Primary lessons learned were the importance of building a trusting partnership with patients through understanding perspectives, being aware of clearly explaining patients' roles, research methods and jargon, providing training, listening to patients' needs and understanding what the partnership means from a patient perspective. For the case study described, patient engagement directly influenced multiple aspects of the study, including study design, implementation, data analysis and dissemination through incorporation of the patients' and caregivers' input and concerns. © The Author 2016. Published by Oxford University Press.

An ecological dynamics rationale to explain home advantage in professional football

NASA Astrophysics Data System (ADS)

Gama, José; Dias, Gonçalo; Couceiro, Micael; Passos, Pedro; Davids, Keith; Ribeiro, João

2016-03-01

Despite clear findings, research on home advantage in team sports lacks a comprehensive theoretical rationale for understanding why this phenomenon is so compelling. The aim of this study was to provide an explanatory theoretical rationale in ecological dynamics for the influence of home advantage observed in research on professional football. We recorded 30 competitive matches and analyzed 13958 passes, from one highly successful team in the Portuguese Premier League, during season 2010/2011. Performance data were analyzed using the Match Analysis Software—Amisco® (version 3.3.7.25), allowing us to characterize team activity profiles. Results were interpreted from an ecological dynamics perspective, explaining how task and environmental constraints of a competitive football setting required performers to continuously co-adapt to teammate behaviors. Despite slight differences in percentage of ball possession when playing home or away, the number of passes achieved by the team, while in possession of the ball, was quite different between home or away venues. When playing at home, the number of passes performed by the team was considerably higher than when playing away. The explanation proposed in this study for a home advantage effect can be understood from studying interpersonal coordination tendencies of team sports players as agents in a complex adaptive system.

Rationale and Roadmap for Moon Exploration

NASA Astrophysics Data System (ADS)

Foing, B. H.; ILEWG Team

We discuss the different rationale for Moon exploration. This starts with areas of scientific investigations: clues on the formation and evolution of rocky planets, accretion and bombardment in the inner solar system, comparative planetology processes (tectonic, volcanic, impact cratering, volatile delivery), records astrobiology, survival of organics; past, present and future life. The rationale includes also the advancement of instrumentation: Remote sensing miniaturised instruments; Surface geophysical and geochemistry package; Instrument deployment and robotic arm, nano-rover, sampling, drilling; Sample finder and collector. There are technologies in robotic and human exploration that are a drive for the creativity and economical competitivity of our industries: Mecha-electronics-sensors; Tele control, telepresence, virtual reality; Regional mobility rover; Autonomy and Navigation; Artificially intelligent robots, Complex systems, Man-Machine interface and performances. Moon-Mars Exploration can inspire solutions to global Earth sustained development: In-Situ Utilisation of resources; Establishment of permanent robotic infrastructures, Environmental protection aspects; Life sciences laboratories; Support to human exploration. We also report on the IAA Cosmic Study on Next Steps In Exploring Deep Space, and ongoing IAA Cosmic Studies, ILEWG/IMEWG ongoing activities, and we finally discuss possible roadmaps for robotic and human exploration, starting with the Moon-Mars missions for the coming decade, and building effectively on joint technology developments.

Investigating Novice and Expert Conceptions of Genetically Modified Organisms

PubMed Central

Potter, Lisa M.; Bissonnette, Sarah A.; Knight, Jonathan D.; Tanner, Kimberly D.

2017-01-01

The aspiration of biology education is to give students tools to apply knowledge learned in the classroom to everyday life. Genetic modification is a real-world biological concept that relies on an in-depth understanding of the molecular behavior of DNA and proteins. This study investigated undergraduate biology students’ conceptions of genetically modified organisms (GMOs) when probed with real-world, molecular and cellular, and essentialist cues, and how those conceptions compared across biology expertise. We developed a novel written assessment tool and administered it to 120 non–biology majors, 154 entering biology majors, 120 advanced biology majors (ABM), and nine biology faculty. Results indicated that undergraduate biology majors rarely included molecular and cellular rationales in their initial explanations of GMOs. Despite ABM demonstrating that they have much of the biology knowledge necessary to understand genetic modification, they did not appear to apply this knowledge to explaining GMOs. Further, this study showed that all undergraduate student populations exhibited evidence of essentialist thinking while explaining GMOs, regardless of their level of biology training. Finally, our results suggest an association between scientifically accurate ideas and the application of molecular and cellular rationales, as well as an association between misconceptions and essentialist rationales. PMID:28821537

Minimum energy efficiency standards for appliances: Old and new economic rationales

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houde, Sebastien; Spurlock, C. Anna

In this study, we revisit Hausman and Joskow (1982)'s economic rationales for appliance minimum energy efficiency standards. In addition to the four market failures they argued could justify appliance standards--energy prices below marginal social cost, consumers underestimating energy prices, consumer discount rates above social discount rates, or principal agent problems--we discuss two additional market failures that are relevant and potentially economically important in this context: market power and innovation market failures. We highlight puzzles uncovered by recent empirical results, and suggest directions future research should take to better understand the normative implications of appliance standards.

Minimum energy efficiency standards for appliances: Old and new economic rationales

DOE PAGES

Houde, Sebastien; Spurlock, C. Anna

2016-09-01

In this study, we revisit Hausman and Joskow (1982)'s economic rationales for appliance minimum energy efficiency standards. In addition to the four market failures they argued could justify appliance standards--energy prices below marginal social cost, consumers underestimating energy prices, consumer discount rates above social discount rates, or principal agent problems--we discuss two additional market failures that are relevant and potentially economically important in this context: market power and innovation market failures. We highlight puzzles uncovered by recent empirical results, and suggest directions future research should take to better understand the normative implications of appliance standards.

Bioethics: A Rationale and a Model

ERIC Educational Resources Information Center

Barman, Charles R.; Rusch, John J.

1978-01-01

Discusses the rationale for and development of an undergraduate bioethics course. Based on experiences with the course, general suggestions are offered to instructors planning to add bioethics to existing curricula. (MA)

Mitogen-activated protein kinase kinase 1/2 inhibition and angiotensin II converting inhibition in mice with cardiomyopathy caused by lamin A/C gene mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muchir, Antoine, E-mail: a.muchir@institut-myologie.org; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY; Wu, Wei

Highlights: • Both ACE and MEK1/2 inhibition are beneficial on cardiac function in Lmna cardiomyopathy. • MEK1/2 inhibitor has beneficial effects beyond ACE inhibition for Lmna cardiomyopathy. • These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor. - Abstract: Background: Mutations in the LMNA gene encoding A-type nuclear lamins can cause dilated cardiomyopathy with or without skeletal muscular dystrophy. Previous studies have shown abnormally increased extracellular signal-regulated kinase 1/2 activity in hearts of Lmna{sup H222P/H222P} mice, a small animal model. Inhibition of this abnormal signaling activity with a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitormore » has beneficial effects on heart function and survival in these mice. However, such treatment has not been examined relative to any standard of care intervention for dilated cardiomyopathy or heart failure. We therefore examined the effects of an angiotensin II converting enzyme (ACE) inhibitor on left ventricular function in Lmna{sup H222P/H222P} mice and assessed if adding a MEK1/2 inhibitor would provide added benefit. Methods: Male Lmna{sup H222P/H222P} mice were treated with the ACE inhibitor benazepril, the MEK1/2 inhibitor selumetinib or both. Transthoracic echocardiography was used to measure left ventricular diameters and fractional shortening was calculated. Results: Treatment of Lmna{sup H222P/H222P} mice with either benazepril or selumetinib started at 8 weeks of age, before the onset of detectable left ventricular dysfunction, lead to statistically significantly increased fractional shortening compared to placebo at 16 weeks of age. There was a trend towards a great value for fractional shortening in the selumetinib-treated mice. When treatment was started at 16 weeks of age, after the onset of left ventricular dysfunction, the addition of selumetinib treatment to benazepril lead to a statistically significant increase in left ventricular fractional shortening at 20 weeks of age. Conclusions: Both ACE inhibition and MEK1/2 inhibition have beneficial effects on left ventricular function in Lmna{sup H222P/H222P} mice and both drugs together have a synergistic benefit when initiated after the onset of left ventricular dysfunction. These results provide further preclinical rationale for a clinical trial of a MEK1/2 inhibitor in addition to standard of care in patients with dilated cardiomyopathy caused by LMNA mutations.« less

Instrument Selection for Randomized Controlled Trials Why This and Not That?

PubMed Central

Records, Kathie; Keller, Colleen; Ainsworth, Barbara; Permana, Paska

2011-01-01

A fundamental linchpin for obtaining rigorous findings in quantitative research involves the selection of survey instruments. Psychometric recommendations are available for the processes for scale development and testing and guidance for selection of established scales. These processes are necessary to address the validity link between the phenomena under investigation, the empirical measures and, ultimately, the theoretical ties between these and the world views of the participants. Detailed information is most often provided about study design and protocols, but far less frequently is a detailed theoretical explanation provided for why specific instruments are chosen. Guidance to inform choices is often difficult to find when scales are needed for specific cultural, ethnic, or racial groups. This paper details the rationale underlying instrument selection for measurement of the major processes (intervention, mediator and moderator variables, outcome variables) in an ongoing study of postpartum Latinas, Madres para la Salud [Mothers for Health]. The rationale underpinning our choices includes a discussion of alternatives, when appropriate. These exemplars may provide direction for other intervention researchers who are working with specific cultural, racial, or ethnic groups or for other investigators who are seeking to select the ‘best’ instrument. Thoughtful consideration of measurement and articulation of the rationale underlying our choices facilitates the maintenance of rigor within the study design and improves our ability to assess study outcomes. PMID:21986392

The Family Value of Information, Community Support, and Experience Study: Rationale, Design, and Methods of a "Family-Centered" Research Study.

PubMed

Reeves, Gloria M; Wehring, Heidi J; Connors, Kathleen M; Bussell, Kristin; Schiffman, Jason; Medoff, Deborah R; Tsuji, Thomas; Walker, Jane; Brown, Alicia; Strobeck, Danielle; Clough, Tammy; Rush, Caitlin B; Riddle, Mark A; Love, Raymond C; Zachik, Albert; Hoagwood, Kimberly; Olin, S Serene; Stephan, Sharon; Okuzawa, Nana; Edwards, Sarah; Baquet, Claudia; dosReis, Susan

2015-12-01

The Patient Protection and Affordable Care Act focuses on improving consumer engagement and patient-centered care. This article describes the design and rationale of a study targeting family engagement in pediatric mental health services. The study is a 90-day randomized trial of a telephone-delivered Family Navigator services versus usual care for parents of Medicaid-insured youth younger than 13 years with serious mental illness. Youth are identified through a pediatric antipsychotic medication preauthorization program. Family Navigators offer peer support to empower and engage parents in their child's recovery. Outcomes include parent report of empowerment, social support, satisfaction with child mental health services, and child functioning as well as claims-based measures of psychotherapy service utilization and antipsychotic medication dosage. The focus on "family-centered" care in this study is strongly supported by the active role of consumers in study design and implementation.

Probing Initial Conditions and Outcomes: Star and Planet Formation Programs within the NIRCam GTO Program

NASA Astrophysics Data System (ADS)

Meyer, Michael; NIRCam Star and Planet Formation Theme Team

2017-06-01

With its extraordinary sensitivity, wavelength coverage from < 1 to 5 microns, 2.2x4.4 arc minute field of view, and diversity of observing modes, NIRCam on JWST offers very powerful capabilities to explore the origins of stars and planets. Here we describe programs planned within the NIRCam GTO Program including: i) extinction mapping of pre-stellar cores; ii) massive star formation; iii) embedded clusters and the end of the IMF; iv) imaging and spectroscopy of young stellar objects; and v) excitation of PAH features. We will describe the scope of each program, selection of observing modes and rationale, as well as provide some explicit examples of program design. We will also review the expected outcomes, illustrating the power of NIRCam to answer questions fundamental to understanding the origins of stars and planets.

Development document for final best conventional technology effluent limitations guidelines for the pharmaceutical manufacturing point source category. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Farrell, T.; Hund, F.

1986-12-01

The document presents the technical rationale for best conventional technology (BCI) effluent limitations guidelines for the pharmaceutical manufacturing point-source category as required by the Clean Water Act of 1977 (P.L. 95-217, the Act). The document describes the technologies considered as the bases for BCT limitations. Section II of this document summarizes the rulemaking process. Sections III through V describe the technical data and engineering analyses used to develop the regulatory technology options. The costs and removals associated with each technology option for each plant and the application of the BCT cost test methodology are presented in Section VI. BCI limitationsmore » bases on the best conventional pollutant control technology are to be achieved by existing direct-discharging facilities.« less

Diagnostic and clinical application value of magnetic resonance imaging (MRI) for progressive massive fibrosis of coal worker pneumoconiosis

PubMed Central

Zhang, Lansheng; Wang, Chun; Yan, Qiuyue; Zhang, Tao; Han, Zhengxiang; Jiang, Guan

2017-01-01

Abstract Rationale: Using magnetic resonance imaging (MRI), we diagnosed pneumoconiosis by identifying the content and distribution of hydrogen protons in the water molecules in different tissues and lesions. Patient concerns: 25 cases of CWP patients with progressive massive fibrosis (PMF) lesions. Diagnoses: Patients were correctly diagnosed, with one case each of Phase I and II pneumoconiosis and 23 cases of Phase III pneumoconiosis. Interventions: None. Outcomes: Through MRI, 39 PMF pneumoconiosis lesions exhibited equal, low or equally low, and uneven signals on T2WI and fat suppression (SPIR) (38/39, 37/39). Lessons: MRI has good specificity to identify the characteristics of PMF lesions of CWP, as well as has high application value for the differential diagnosis of lung cancer and other lung tumor-like lesions. PMID:28514304

Seattle wide-area information for travelers (SWIFT) : communications study

DOT National Transportation Integrated Search

1998-10-19

This document discusses the rationale, procedures, results, discussion and conclusions of the Seattle Wide-area Information for Travelers (SWIFT) Communications Study evaluation that was conducted for the Washington State Department of Transportation...

Lessons learned from 15 years of non-grades-based selection for medical school.

PubMed

Stegers-Jager, Karen M

2018-01-01

Thirty years ago, it was suggested in the Edinburgh Declaration that medical school applicants should be selected not only on academic, but also on non-academic, attributes. The main rationale behind extending medical school selection procedures with the evaluation of (non-academic) personal qualities is that this will lead to the selection of students who will perform better as a doctor than those who are selected on the basis of academic measures only. A second rationale is the expectation that this will lead to a representative health workforce as a result of reduced adverse impact. The aims of this paper are (i) to describe what can be learned about the use of selection criteria other than grades from over 15 years of Dutch experience and (ii) to summarise current knowledge on the issue of adverse impact in relation to non-grades-based selection. A narrative review was undertaken of the (published) evidence that has resulted from non-grades-based school-specific selection procedures in the Netherlands and from recent explorations of the effect of the use of non-grades-based selection criteria on student diversity. The Dutch evidence is grouped into five key themes: the effect of participation in voluntary selection procedures, the assessment of pre-university extracurricular activities, the use of work samples, Dutch experiences with situational judgement tests and the effects of changing circumstances. This is followed by several lessons learned for medical schools that aim to increase their student diversity. Over the last 30 years, important steps towards reliable and valid methods for measuring non-academic abilities have been taken. The current paper describes several lessons that can be learned from the steps taken in the Dutch context. The importance of sharing evidence gathered around the globe and building on this evidence to reach our goal of predicting who will be a good doctor is acknowledged. © 2017 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

PubMed Central

Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

2015-01-01

Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications.

PubMed

Hall, Wayne; Kozlowski, Lynn T

2018-04-01

To examine briefly the (i) rationales for two policy proposals in the United States to make it mandatory for cigarettes to contain very low levels of nicotine and to legalize cannabis for recreational use by adults; and (ii) possible lessons that participants in each policy debate may learn from each other. We briefly describe the diverging policies towards cannabis and tobacco in the United States, explain and critically analyse their rationales and discuss possible policy lessons. Advocates of cannabis legalization have argued that prohibition has been an ineffective and expensive policy that penalizes ethnic minority users unjustly of a drug that is far less harmful than alcohol. The prohibition of traditional tobacco cigarettes has been advocated as a way to eliminate cigarette smoking. These proposals embody very different attitudes towards the harms of recreational adult drug use. Advocates of nicotine prohibition demand that alternative methods of nicotine delivery must be shown to be completely safe before adults are allowed to use them. Advocates of tobacco prohibition ignore evidence that smokers may not use these products and the likelihood of expanding the illicit tobacco market. Advocates of legalizing and regulating recreational cannabis ignore the need to tax and regulate sales in order to minimize the harms of heavy use. It is not clear that the prohibition of adult use has a useful role to play in the regulation of either cannabis or tobacco. If both products remain legal, the goals of regulating tobacco and cannabis products should be to restrict youth access, promote the use of the least harmful products, provide users with evidence-based information on both absolute and differential product risks of use and use differential taxes and marketing controls to promote ways of using these products that cause the least harm to their users. © 2017 Society for the Study of Addiction.

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation.

PubMed

Acosta, Joie D; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S

2016-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014-2015 school year. The study's rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area.

Tracheal lacerations after endotracheal intubation: a proposed morphological classification to guide non-surgical treatment.

PubMed

Cardillo, Giuseppe; Carbone, Luigi; Carleo, Francesco; Batzella, Sandro; Jacono, Raffaelle Dello; Lucantoni, Gabriele; Galluccio, Giovanni

2010-03-01

Postintubation tracheobronchial lacerations (PITLs) are traditionally managed surgically. We sought to evaluate the rationale for non-surgical management of PITL. From January 2003 to November 2008, 30 patients with PITL were observed in our institution. PITL were graded as follows: Level I - mucosal or submucosal tracheal involvement without mediastinal emphysema and without oesophageal injury; Level II - tracheal lesion up to the muscular wall with subcutaneous or mediastinal emphysema without oesophageal injury or mediastinitis; Level IIIA - complete laceration of the tracheal wall with oesophageal or mediastinal soft-tissue hernia without oesophageal injury or mediastinitis; Level IIIB - any laceration of the tracheal wall with oesophageal injury or mediastinitis. All patients with Level I, II and IIIA PITL were treated conservatively with endoscopic instillation of fibrin glue (Tissucol, Baxter Healthcare, Deerfield, MA, USA). All patients with Level I (n=3), II (n=24) and IIIA (n=2) PITL were successfully treated conservatively. The patient with a Level IIIB injury underwent posterolateral thoracotomy repair of the trachea. No mortality was reported. Mean hospital stay was 12.9 days. Flexible bronchoscopy at 7, 28, 90 and 180 days showed no abnormalities. Complete healing was attained in all patients by day 28. Level I or II PITL should be managed non-surgically. When adequate respiratory status is present, Level IIIA PITL can be managed conservatively in selected institutions only, because these injuries are high-risk injuries. Any PITL associated with injury involving the oesophagus or with mediastinitis (Level IIIB) must be treated as soon as possible by surgery. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Comparison of self-citation by peer reviewers in a journal with single-blind peer review versus a journal with open peer review.

PubMed

Levis, Alexander W; Leentjens, Albert F G; Levenson, James L; Lumley, Mark A; Thombs, Brett D

2015-12-01

Some peer reviewers may inappropriately, or coercively request that authors include references to the reviewers' own work. The objective of this study was to evaluate whether, compared to reviews for a journal with single-blind peer review, reviews for a journal with open peer review included (1) fewer self-citations; (2) a lower proportion of self-citations without a rationale; and (3) a lower ratio of proportions of citations without a rationale in self-citations versus citations to others' work. Peer reviews for published manuscripts submitted in 2012 to a single-blind peer review journal, the Journal of Psychosomatic Research, were previously evaluated (Thombs et al., 2015). These were compared to publically available peer reviews of manuscripts published in 2012 in an open review journal, BMC Psychiatry. Two investigators independently extracted data for both journals. There were no significant differences between journals in the proportion of all reviewer citations that were self-citations (Journal of Psychosomatic Research: 71/225, 32%; BMC Psychiatry: 90/315, 29%; p=.50), or in the proportion of self-citations without a rationale (Journal of Psychosomatic Research: 15/71, 21%; BMC Psychiatry: 12/90, 13%; p=.21). There was no significant difference between journals in the proportion of self-citations versus citations to others' work without a rationale (p=.31). Blind and open peer review methodologies have distinct advantages and disadvantages. The present study found that, in reasonably similar journals that use single-blind and open review, there were no substantive differences in the pattern of peer reviewer self-citations. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates To Improve Human Health.

PubMed

Deehan, Edward C; Duar, Rebbeca M; Armet, Anissa M; Perez-Muñoz, Maria Elisa; Jin, Mingliang; Walter, Jens

2017-09-01

There is a clear association between the gastrointestinal (GI) microbiome and the development of chronic noncommunicable diseases, providing a rationale for the development of strategies that target the GI microbiota to improve human health. In this article, we discuss the potential of supplementing the human diet with nondigestible fermentable carbohydrates (NDFCs) to modulate the composition, structure, diversity, and metabolic potential of the GI microbiome in an attempt to prevent or treat human disease. The current concepts by which NDFCs can be administered to humans, including prebiotics, fermentable dietary fibers, and microbiota-accessible carbohydrates, as well as the mechanisms by which these carbohydrates exert their health benefits, are discussed. Epidemiological research presents compelling evidence for the health effects of NDFCs, with clinical studies providing further support for some of these benefits. However, rigorously designed human intervention studies with well-established clinical markers and microbial endpoints are still essential to establish (i) the clinical efficiency of specific NDFCs, (ii) the causal role of the GI microbiota in these effects, (iii) the underlying mechanisms involved, and (iv) the degree by which inter-individual differences between GI microbiomes influence these effects. Such studies would provide the mechanistic understanding needed for a systematic application of NDFCs to improve human health via GI microbiota modulation while also allowing the personalization of these dietary strategies.

Collection of real-world data on nivolumab's effectiveness in renal cell carcinoma: rationale for an observational study.

PubMed

Bedke, Jens; Grimm, Marc-Oliver; Grünwald, Viktor

2018-05-01

Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth (women) most frequent cancer in western countries. After one or more lines of VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in patients with metastatic RCC. Nivolumab is the first, and so far, only approved PD-1 immune checkpoint inhibitor to demonstrate a gain in overall survival in RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a prospective, noninterventional cohort study investigating the effectiveness of nivolumab. This systematic collection of real-world effectiveness data will recruit 323 patients with advanced RCC to provide a precise estimate for overall survival over a 5-year follow-up period (Trial registration: NCT02940639).

Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.

PubMed

Ghosh, Sougata; More, Piyush; Derle, Abhishek; Patil, Ajay B; Markad, Pramod; Asok, Adersh; Kumbhar, Navanath; Shaikh, Mahemud L; Ramanamurthy, Boppana; Shinde, Vaishali S; Dhavale, Dilip D; Chopade, Balu A

2014-01-01

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

PubMed Central

Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

2013-01-01

Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

Female genital cosmetic and plastic surgery: a review.

PubMed

Goodman, Michael P

2011-06-01

This review studies rationale and outcome of vulvovaginal aesthetic surgery. Discuss procedures designed to alter genital appearance and function; investigate sexual, philosophical, and ethical issues; examine outcomes. (i) Medline search of the existing literature utilizing terms labiaplasty, clitoral hood reduction, hymenoplasty (HP), vaginoplasty (VP), perineoplasty (PP), female genital surgery, sexual satisfaction/body image, and anterior/posterior colporrhaphy; (ii) references from bibliographies of papers found through the literature search and in the author's reading of available literature. (i) Demographics and psychosexual dynamics of women requesting female genital plastic/cosmetic surgery; (ii) overall and sexual satisfaction of subjects undergoing these procedures. The majority of studies regarding patient satisfaction and sexual function after vaginal aesthetic and functional plastic procedures report beneficial results, with overall patient satisfaction in the 90-95% range, sexual satisfaction over 80-85%. These data are supported by outcome data from nonelective vaginal support procedures. Complications appear minor and acceptable to patients. There are little data available regarding outcomes and satisfaction of HP, or function during the rigors of subsequent vaginal childbirth, although the literature contains no case reports of labiaplasty disruption during parturition. Women requesting labiaplasty and reduction of their clitoral hoods do so for both cosmetic and functional (chafing, interference with coitus, interference with athletic activities, etc.) reasons, while patients requesting VP and/or PP do so in order to increase friction and sexual satisfaction, occasionally for aesthetic reasons. Patients appear generally happy with outcomes. The majority of patients undergoing genital plastic surgery report overall satisfaction and subjective enhancement of sexual function and body image, but the literature is retrospective. Female genital plastic surgery procedures appear to fulfill the majority of patient's desires for cosmetic and functional improvement, as well as enhancement of the sexual experience. Little information is available regarding HP outcomes. © 2011 International Society for Sexual Medicine.

Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

PubMed Central

Ghosh, Sougata; More, Piyush; Derle, Abhishek; Patil, Ajay B.; Markad, Pramod; Asok, Adersh; Kumbhar, Navanath; Shaikh, Mahemud L.; Ramanamurthy, Boppana; Shinde, Vaishali S.; Dhavale, Dilip D.; Chopade, Balu A.

2014-01-01

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus. PMID:25216353

Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure.

PubMed

Arnold, Amy C; Okamoto, Luis E; Gamboa, Alfredo; Black, Bonnie K; Raj, Satish R; Elijovich, Fernando; Robertson, David; Shibao, Cyndya A; Biaggioni, Italo

2016-02-01

Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that plasma angiotensin II is elevated and acts at AT1 (angiotensin type 1) receptors to contribute to hypertension in these patients. Because aldosterone and angiotensin II can also bind mineralocorticoid receptors to elevate blood pressure, we hypothesized that mineralocorticoid receptor activation plays a role in the hypertension of autonomic failure. To test this hypothesis, we determined the acute effects of the mineralocorticoid receptor antagonist eplerenone (50 mg, oral) versus placebo on supine blood pressure in a randomized, double-blind, crossover study. Medications were given at 8:00 pm with blood pressure recorded every 2 hours for 12 hours. Ten primary autonomic failure patients with supine hypertension completed this study (7 pure autonomic failure, 2 multiple system atrophy, 1 parkinson's disease; 7 male; 70±2 years of age). Eplerenone maximally reduced supine systolic blood pressure by 32±6 mm Hg at 8 hours after administration (versus 8±10 mm Hg placebo, P=0.016), with no effect on nocturia (12-hour urine volume: 985±134 mL placebo versus 931±94 mL eplerenone, P=0.492; nocturnal weight loss: -1.19±0.15 kg placebo versus -1.18±0.15 kg eplerenone, P=0.766). These findings suggest that inappropriate mineralocorticoid receptor activation contributes to the hypertension of autonomic failure, likely independent of canonical mineralocorticoid effects, and provides rationale for use of eplerenone in these patients. © 2015 American Heart Association, Inc.

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age?

PubMed Central

Thia, Lena P; Calder, Alistair; Stocks, Janet; Bush, Andrew; Owens, Catherine M; Wallis, Colin; Young, Carolyn; Sullivan, Yvonne; Wade, Angie; McEwan, Angus; Brody, Alan S

2014-01-01

Rationale Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants. Objectives The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy. Methods A multicentre observational study of early pulmonary lung disease in NBS infants with CF at age 1 year using volume-controlled chest CT performed under general anaesthetic. Main results 65 infants with NBS-diagnosed CF had chest CT in three centres. Small insignificant variations in lung recruitment manoeuvres but significant centre differences in radiation exposures were found. Despite experienced scorers and prior training, with the exception of air trapping, inter- and intraobserver agreement on Brody-II score was poor to fair (eg, interobserver total score mean (95% CI) κ coefficient: 0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score ≥12 (ie, ≥5% maximum possible) by either scorer. Conclusions In NBS infants with CF, CT changes were very mild at 1 year, and assessment of air trapping was the only reproducible outcome. CT is thus of questionable value in infants of this age, unless an improved scoring system for use in mild CF disease can be developed. PMID:24132911

Mixed-methods designs in mental health services research: a review.

PubMed

Palinkas, Lawrence A; Horwitz, Sarah M; Chamberlain, Patricia; Hurlburt, Michael S; Landsverk, John

2011-03-01

Despite increased calls for use of mixed-methods designs in mental health services research, how and why such methods are being used and whether there are any consistent patterns that might indicate a consensus about how such methods can and should be used are unclear. Use of mixed methods was examined in 50 peer-reviewed journal articles found by searching PubMed Central and 60 National Institutes of Health (NIH)-funded projects found by searching the CRISP database over five years (2005-2009). Studies were coded for aims and the rationale, structure, function, and process for using mixed methods. A notable increase was observed in articles published and grants funded over the study period. However, most did not provide an explicit rationale for using mixed methods, and 74% gave priority to use of quantitative methods. Mixed methods were used to accomplish five distinct types of study aims (assess needs for services, examine existing services, develop new or adapt existing services, evaluate services in randomized controlled trials, and examine service implementation), with three categories of rationale, seven structural arrangements based on timing and weighting of methods, five functions of mixed methods, and three ways of linking quantitative and qualitative data. Each study aim was associated with a specific pattern of use of mixed methods, and four common patterns were identified. These studies offer guidance for continued progress in integrating qualitative and quantitative methods in mental health services research consistent with efforts by NIH and other funding agencies to promote their use.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

PubMed

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

Public policy versus individual rights and responsibility: an economist's perspective.

PubMed

Chaloupka, Frank J

2011-09-01

Interventions to reduce childhood obesity entail ethical considerations. Although a rationale exists for government to intervene in a way that limits individual rights while protecting the public's health, a clear economic rationale also exists. The markets for goods and services that contribute to obesity are characterized by multiple failures that create an economic rationale for government to intervene (eg, consumers' lack of accurate information regarding obesogenic foods and beverages). If effective public policies for reducing obesity and its consequences are to be developed and implemented, individual rights and government interests must be balanced.

Four Futures for Social Studies.

ERIC Educational Resources Information Center

Morrissett, Irving

The current status of social studies education provides information for assessing and predicting future trends in social studies education. A 3-year study, "Social Studies Priorities and Needs," found that: social studies/social science educators are concerned with constructing a rationale and definition of social studies; the dominant approach to…

Building Scientific Confidence in the Development and ...

EPA Pesticide Factsheets

Acceptance of read-across is an ongoing challenge and several efforts are underway to identify and address major uncertainties associated with read-across. Several approaches have been proposed but to date few case studies if any have evaluated how Tox21 approaches may be instructive in substantiating category rationales, or indeed their associated read-across justifications. Here we have identified a handful of former OECD HPV categories and evaluated to what extent data from HTS assays notably that generated through ToxCast are helpful in strengthening the rationale underlying those categories and their associated read-across. A handful of categories were identified based on the overlap between the HPV chemicals and the ToxCast inventory. Those selected included the ethylene glycols and primary aliphatic alcohols categories. The findings so far are mixed, highlighting the importance of carefully interpreting the ToxCast data in its appropriate context. Slide or platform presentation at the SOT 2016 annual meeting. This is an proof of concept evaluation for a handful of regulatory categories to determine whether there is any added value of considering bioactivity data to substantiate an existing category rationale.

Environmental Studies Model.

ERIC Educational Resources Information Center

George, David R.

1986-01-01

Presents a model of an environmental studies course that reflects a spaceship earth philosophy. Includes a rationale and a listing of concepts and processes for this action oriented program. Suggests several interdisciplinary experiences that emphasize problem-solving and decision-making skills. (ML)

A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics.

PubMed

Abraham, William T; Burkhoff, Daniel; Nademanee, Koonlawee; Carson, Peter; Bourge, Robert; Ellenbogen, Kenneth A; Parides, Michael; Kadish, Alan

2008-10-01

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.

Insect-like flapping wing mechanism based on a double spherical Scotch yoke.

PubMed

Galiński, Cezary; Zbikowski, Rafał

2005-06-22

We describe the rationale, concept, design and implementation of a fixed-motion (non-adjustable) mechanism for insect-like flapping wing micro air vehicles in hover, inspired by two-winged flies (Diptera). This spatial (as opposed to planar) mechanism is based on the novel idea of a double spherical Scotch yoke. The mechanism was constructed for two main purposes: (i) as a test bed for aeromechanical research on hover in flapping flight, and (ii) as a precursor design for a future flapping wing micro air vehicle. Insects fly by oscillating (plunging) and rotating (pitching) their wings through large angles, while sweeping them forwards and backwards. During this motion the wing tip approximately traces a "figure-of-eight" or a "banana" and the wing changes the angle of attack (pitching) significantly. The kinematic and aerodynamic data from free-flying insects are sparse and uncertain, and it is not clear what aerodynamic consequences different wing motions have. Since acquiring the necessary kinematic and dynamic data from biological experiments remains a challenge, a synthetic, controlled study of insect-like flapping is not only of engineering value, but also of biological relevance. Micro air vehicles are defined as flying vehicles approximately 150 mm in size (hand-held), weighing 50-100g, and are developed to reconnoitre in confined spaces (inside buildings, tunnels, etc.). For this application, insect-like flapping wings are an attractive solution and hence the need to realize the functionality of insect flight by engineering means. Since the semi-span of the insect wing is constant, the kinematics are spatial; in fact, an approximate figure-of-eight/banana is traced on a sphere. Hence a natural mechanism implementing such kinematics should be (i) spherical and (ii) generate mathematically convenient curves expressing the figure-of-eight/banana shape. The double spherical Scotch yoke design has property (i) by definition and achieves (ii) by tracing spherical Lissajous curves.

The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome.

PubMed

Legro, Richard S; Kunselman, Allen R; Brzyski, Robert G; Casson, Peter R; Diamond, Michael P; Schlaff, William D; Christman, Gregory M; Coutifaris, Christos; Taylor, Hugh S; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-05-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. Copyright © 2012 Elsevier Inc. All rights reserved.

Insect-like flapping wing mechanism based on a double spherical Scotch yoke

PubMed Central

Galiński, Cezary; Żbikowski, Rafał

2005-01-01

We describe the rationale, concept, design and implementation of a fixed-motion (non-adjustable) mechanism for insect-like flapping wing micro air vehicles in hover, inspired by two-winged flies (Diptera). This spatial (as opposed to planar) mechanism is based on the novel idea of a double spherical Scotch yoke. The mechanism was constructed for two main purposes: (i) as a test bed for aeromechanical research on hover in flapping flight, and (ii) as a precursor design for a future flapping wing micro air vehicle. Insects fly by oscillating (plunging) and rotating (pitching) their wings through large angles, while sweeping them forwards and backwards. During this motion the wing tip approximately traces a ‘figure-of-eight’ or a ‘banana’ and the wing changes the angle of attack (pitching) significantly. The kinematic and aerodynamic data from free-flying insects are sparse and uncertain, and it is not clear what aerodynamic consequences different wing motions have. Since acquiring the necessary kinematic and dynamic data from biological experiments remains a challenge, a synthetic, controlled study of insect-like flapping is not only of engineering value, but also of biological relevance. Micro air vehicles are defined as flying vehicles approximately 150 mm in size (hand-held), weighing 50–100 g, and are developed to reconnoitre in confined spaces (inside buildings, tunnels, etc.). For this application, insect-like flapping wings are an attractive solution and hence the need to realize the functionality of insect flight by engineering means. Since the semi-span of the insect wing is constant, the kinematics are spatial; in fact, an approximate figure-of-eight/banana is traced on a sphere. Hence a natural mechanism implementing such kinematics should be (i) spherical and (ii) generate mathematically convenient curves expressing the figure-of-eight/banana shape. The double spherical Scotch yoke design has property (i) by definition and achieves (ii) by tracing spherical Lissajous curves. PMID:16849181

THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME II (PPCOS II) TRIAL: RATIONALE AND DESIGN OF A DOUBLE-BLIND RANDOMIZED TRIAL OF CLOMIPHENE CITRATE AND LETROZOLE FOR THE TREATMENT OF INFERTILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

PubMed Central

Legro, Richard S.; Kunselman, Allen R.; Brzyski, Robert G.; Casson, Peter R.; Diamond, Michael P.; Schlaff, William D.; Christman, Gregory M.; Coutifaris, Christos; Taylor, Hugh S.; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-01-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50 mg every day for 5 days (day 3–7 of cycle), or B) letrozole 2.5 mg every day for 5 days (day 3–7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (× 5 days) or 7.5 mg of letrozole a day (× 5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. PMID:22265923

First Reconsideration Decision and Rationale: Nutrient and Sediment TMDLs for the Indian Creek Watershed, Pennsylvania

EPA Pesticide Factsheets

Reconsideration Decision and Rationale: Nutrient and Sediment TMDLs for the Indian Creek Watershed, Pennsylvania: Established by the U.S. Environmental Protection Agency, Region 3, Philadelphia, PA. March 21, 2014. 6 Documents, below

High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences

PubMed Central

Ronninger, Marcus; Shchetynsky, Klementy; Franke, Andre; Nöthen, Markus M.; Müller-Quernheim, Joachim; Schreiber, Stefan; Adrianto, Indra; Karakaya, Bekir; van Moorsel, Coline H. M.; Navratilova, Zdenka; Kolek, Vitezslav; Rybicki, Benjamin A.; Iannuzzi, Michael C.; Petrek, Martin; Grutters, Jan C.; Montgomery, Courtney; Fischer, Annegret; Eklund, Anders; Padyukov, Leonid; Grunewald, Johan

2016-01-01

Rationale: Sarcoidosis is a multisystem disease of unknown cause. Löfgren’s syndrome (LS) is a characteristic subgroup of sarcoidosis that is associated with a good prognosis in sarcoidosis. However, little is known about its genetic architecture or its broader phenotype, non-LS sarcoidosis. Objectives: To address the genetic architecture of sarcoidosis phenotypes, LS and non-LS. Methods: An association study in a white Swedish cohort of 384 LS, 664 non-LS, and 2,086 control subjects, totaling 3,134 subjects using a fine-mapping genotyping platform was conducted. Replication was performed in four independent cohorts, three of white European descent (Germany, n = 4,975; the Netherlands, n = 613; and Czech Republic, n = 521), and one of black African descent (United States, n = 1,657), totaling 7,766 subjects. Measurements and Main Results: A total of 727 LS-associated variants expanding throughout the extended major histocompatibility complex (MHC) region and 68 non-LS–associated variants located in the MHC class II region were identified and confirmed. A shared overlap between LS and non-LS defined by 17 variants located in the MHC class II region was found. Outside the MHC region, two LS-associated loci, in ADCY3 and between CSMD1 and MCPH1, were observed and replicated. Conclusions: Comprehensive and integrative analyses of genetics, transcription, and pathway modeling on LS and non-LS indicates that these sarcoidosis phenotypes have different genetic susceptibility, genomic distributions, and cellular activities, suggesting distinct molecular mechanisms in pathways related to immune response with a common region. PMID:26651848

Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin.

PubMed

Bogenschutz, Michael P

2013-03-01

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Photochemical Reaction Altered Cardiac Toxicity of Diesel Exhaust Inhalation

EPA Science Inventory

Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled diesel exhaust and compared with photochemically altered d...

A Transnational Outlook.

ERIC Educational Resources Information Center

Channing, Rose M.; Blanco, Virgil

1980-01-01

After providing a rationale for international education, describes Middlesex County College's: (1) International Studies Institute for faculty and administrators; (2) affordable overseas programs for students; (3) survey of international trade training needs; (4) international business promotion efforts; and (5) new international studies courses…

Framing bioremediation decision making as negotiation: Rationale & guidelineFraming bioremediation decision making as negotiation: Rationale & guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bjornstad, David J.; Wolfe, Amy K.

Framing remediation decision making as negotiation: (1) social choice, not technology choice; (2) prompts decision makers to identify interested and affected parties, anticipate objections, effectively address and ameliorate objections, and avoid unacceptable decisions.

Corporate incentives for promoting safety belt use : rationale, guidelines, and examples

DOT National Transportation Integrated Search

1982-10-01

This manual was designed to teach the corporate executive successful strategies for implementing and evaluating a successful industry-based program to motivate employee safety belt use. A rationale is given for the general approach; and specific guid...

Proposed energy conservation contingency plan: emergency restrictions on advertising lighting. Authorities, need, rationale, and operation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The emergency restrictions on advertising lighting proposed in Energy Conservation Contingency Plan No. 5 of 1977 are presented. A statement is given on the need for rationale and operation of the Contingency Plan.

[An expert system of aiding decision making in breast pathology connected to a clinical data base].

PubMed

Brunet, M; Durrleman, S; Ferber, J; Ganascia, J G; Hacene, K; Hirt, F; Jouniaux, F; Meeus, L

1987-01-01

The René Huguenin Cancer Center holds a medical file for each patient which is intended to store and process medical data. Since 1970, we introduced computerization: a development plan was elaborated and simultaneously a statistical software (Clotilde--GSI/CFRO) was selected. Thus, we now have access to a large database, structured according to medical rationale, and utilizable with methods of artificial intelligence towards three objectives: improved data acquisition, decision making and exploitation. The first application was to breast pathology, which represents one of the Center's primary activities. The structure of the data concerning patients is by all criteria part of the medical knowledge. This information needs to be presented as well as processed with a suitable language. To this end, we chose a language-oriented object, Mering II, usable with Apple and IBM 4 micro-computers. This project has already allowed to work out an operational model.

Remedial action suitability for the Cornhusker Army Ammunition Plant site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nonavinakere, S.; Rappa, P. III

1995-12-31

Numerous Department of Defense (DOD) sites across the nation are contaminated with explosive wastes due to munitions production during World War II, Korean Conflict and Vietnam Conflict. Production activities included explosives manufacturing, loading, packing, assembling, machining, casting and curing. Contaminants often present at these sites include TNT, RDX, HMX, Tetryl 2,4-DNT, 2,6-DNT, 1,3-DNB, 1,3,5-TNB and nitrobenzene. The Cornhusker Army Ammunition Plant (CAAP) is one such DOD site that has been determined to be contaminated with explosives. The CAAP is located approximately 2 miles west of the City of Grand Island in Hall County, Nebraska. The plant produced artillery, bombs, boosters,more » supplementary charges and various other experimental explosives. The purpose of this paper is to provide an overview of the site background, review of the remedial alternatives evaluation process and rationale behind the selection of present remedial action.« less

The CRAF/Cassini power subsystem - Preliminary design update

NASA Technical Reports Server (NTRS)

Atkins, Kenneth L.; Brisendine, Philip; Clark, Karla; Klein, John; Smith, Richard

1991-01-01

A chronology is provided of the rationale leading from the early Mariner spacecraft to the CRAF/Cassini Mariner Mark II power subsystem architecture. The display pathway began with a hybrid including a solar photovoltaic array, a radioisotope thermoelectric generator (RTG), and a battery supplying a power profile with a peak loading of about 300 W. The initial concept was to distribute power through a new solid-state, programmable switch controlled by an embedded microprocessor. As the overall mission, science, and project design matured, the power requirements increased. The design evolved from the hybrid to two RTG plus batteries to meet peak loadings of near 500 W in 1989. Later that year, circumstances led to abandonment of the distributed computer concept and a return to centralized control. Finally, as power requirements continued to grow, a third RTG was added to the design and the battery removed, with the return to the discharge-controller for transients during fault recovery procedures.

Biologic Treatments for Sports Injuries II Think Tank—Current Concepts, Future Research, and Barriers to Advancement, Part 2

PubMed Central

Murray, Iain R.; LaPrade, Robert F.; Musahl, Volker; Geeslin, Andrew G.; Zlotnicki, Jason P.; Mann, Barton J.; Petrigliano, Frank A.

2016-01-01

Rotator cuff tears are common and result in considerable morbidity. Tears within the tendon substance or at its insertion into the humeral head represent a considerable clinical challenge because of the hostile local environment that precludes healing. Tears often progress without intervention, and current surgical treatments are inadequate. Although surgical implants, instrumentation, and techniques have improved, healing rates have not improved, and a high failure rate remains for large and massive rotator cuff tears. The use of biologic adjuvants that contribute to a regenerative microenvironment have great potential for improving healing rates and function after surgery. This article presents a review of current and emerging biologic approaches to augment rotator cuff tendon and muscle regeneration focusing on the scientific rationale, preclinical, and clinical evidence for efficacy, areas for future research, and current barriers to advancement and implementation. PMID:27099865

The future of South East Asian rainforests in a changing landscape and climate.

PubMed

Hector, Andy; Fowler, David; Nussbaum, Ruth; Weilenmann, Maja; Walsh, Rory P D

2011-11-27

With a focus on the Danum Valley area of Sabah, Malaysian Borneo, this special issue has as its theme the future of tropical rainforests in a changing landscape and climate. The global environmental context to the issue is briefly given before the contents and rationale of the issue are summarized. Most of the papers are based on research carried out as part of the Royal Society South East Asia Rainforest Research Programme. The issue is divided into five sections: (i) the historical land-use and land management context; (ii) implications of land-use change for atmospheric chemistry and climate change; (iii) impacts of logging, forest fragmentation (particularly within an oil palm plantation landscape) and forest restoration on ecosystems and their functioning; (iv) the response and resilience of rainforest systems to climatic and land-use change; and (v) the scientific messages and policy implications arising from the research findings presented in the issue.

Fluid status monitoring with a wireless network to reduce cardiovascular-related hospitalizations and mortality in heart failure: rationale and design of the OptiLink HF Study (Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink).

PubMed

Brachmann, Johannes; Böhm, Michael; Rybak, Karin; Klein, Gunnar; Butter, Christian; Klemm, Hanno; Schomburg, Rolf; Siebermair, Johannes; Israel, Carsten; Sinha, Anil-Martin; Drexler, Helmut

2011-07-01

The Optimization of Heart Failure Management using OptiVol Fluid Status Monitoring and CareLink (OptiLink HF) study is designed to investigate whether OptiVol fluid status monitoring with an automatically generated wireless CareAlert notification via the CareLink Network can reduce all-cause death and cardiovascular hospitalizations in an HF population, compared with standard clinical assessment. Methods Patients with newly implanted or replacement cardioverter-defibrillator devices with or without cardiac resynchronization therapy, who have chronic HF in New York Heart Association class II or III and a left ventricular ejection fraction ≤35% will be eligible to participate. Following device implantation, patients are randomized to either OptiVol fluid status monitoring through CareAlert notification or regular care (OptiLink 'on' vs. 'off'). The primary endpoint is a composite of all-cause death or cardiovascular hospitalization. It is estimated that 1000 patients will be required to demonstrate superiority of the intervention group to reduce the primary outcome by 30% with 80% power. The OptiLink HF study is designed to investigate whether early detection of congestion reduces mortality and cardiovascular hospitalization in patients with chronic HF. The study is expected to close recruitment in September 2012 and to report first results in May 2014.

Prevalence, Correlates, and Prognosis of Peripheral Artery Disease in Rural Ecuador—Rationale, Protocol, and Phase I Results of a Population-Based Survey: An Atahualpa Project-Ancillary Study

PubMed Central

Del Brutto, Oscar H.; Sedler, Mark J.; Mera, Robertino M.; Castillo, Pablo R.; Cusick, Elizabeth H.; Gruen, Jadry A.; Phelan, Kelsie J.; Del Brutto, Victor J.; Zambrano, Mauricio; Brown, David L.

2014-01-01

Background. Little is known on the prevalence of peripheral artery disease (PAD) in developing countries. Study design. Population-based study in Atahualpa. In Phase I, the Edinburgh claudication questionnaire (ECQ) was used for detection of suspected symptomatic PAD; persons with a negative ECQ but a pulse pressure ≥65 mmHg were suspected of asymptomatic PAD. In Phase II, the ankle-brachial index will be used to test reliability of screening instruments and to determine PAD prevalence. In Phase III, participants will be followed up to estimate the relevance of PAD as a predictor of vascular outcomes. Results. During Phase I, 665 Atahualpa residents aged ≥40 years were enrolled (mean age: 59.5 ± 12.6 years, 58% women). A poor cardiovascular health status was noticed in 464 (70%) persons of which 27 (4%) had a stroke and 14 (2%) had ischemic heart disease. Forty-four subjects (7%) had suspected symptomatic PAD and 170 (26%) had suspected asymptomatic PAD. Individuals with suspected PAD were older, more often women, and had a worse cardiovascular profile than those with nonsuspected PAD. Conclusions. Prevalence of suspected PAD in this underserved population is high. Subsequent phases of this study will determine whether prompt detection of PAD is useful to reduce the incidence of catastrophic vascular diseases in the region. PMID:25389500

ABSORB II randomized controlled trial: a clinical evaluation to compare the safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable vascular scaffold system against the XIENCE everolimus-eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions: rationale and study design.

PubMed

Diletti, Roberto; Serruys, Patrick W; Farooq, Vasim; Sudhir, Krishnankutty; Dorange, Cecile; Miquel-Hebert, Karine; Veldhof, Susan; Rapoza, Richard; Onuma, Yoshinobu; Garcia-Garcia, Hector M; Chevalier, Bernard

2012-11-01

Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions. Copyright © 2012 Mosby, Inc. All rights reserved.

Design of Peptide Immunotherapies for MHC Class-II-Associated Autoimmune Disorders

PubMed Central

2013-01-01

Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC) is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL), or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA) is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS) patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP) peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders. PMID:24324511

The chemistry of wine polyphenolic C-glycosidic ellagitannins targeting human topoisomerase II.

PubMed

Quideau, Stéphane; Jourdes, Michael; Lefeuvre, Dorothée; Montaudon, Danièle; Saucier, Cédric; Glories, Yves; Pardon, Patrick; Pourquier, Philippe

2005-11-04

Polyphenolic nonahydroxyterphenoyl-containing C-glycosidic oak ellagitannins are found in wine as a result of the aging of this beverage in oak-made barrels. Once in the slightly acidic wine (pH approximately 3-4), some of these complex natural products such as (-)-vescalagin (1), but not its C-1 epimer (-)-castalagin (2), can capture grape-derived nucleophilic entities such as ethanol, the flavanols catechin (10a) and epicatechin (10b), the anthocyanin oenin (13b), and the thiolic glutathione (16) to furnish condensation products with retention of configuration at the C-1 locus. A computer-aided rationale of this high diastereoselectivity is given. These condensation products can contribute to the modulation of organoleptic properties of the wine, as evidenced by the 23 nm bathochromic shift color absorbance observed with the novel oenin-based anthocyano-ellagitannin (15b). Hydrolysis of 1 under solvolytic conditions furnished another novel compound that we refer to as vescalene (21), in addition to the known (-)-vescalin (18). Of pharmacological importance is the fact that most of these found-in-wine water-soluble ellagitannin derivatives are much more potent than etoposide (VP-16) at inhibiting top2-mediated DNA decatenation in vitro (top2=topoisomerase II)). The known (-)-vescalin (18) and the novel vescalene (21) fully inhibited top2 at 10 microM concentration!

A predator-prey model with a holling type I functional response including a predator mutual interference

USGS Publications Warehouse

Seo, G.; DeAngelis, D.L.

2011-01-01

The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

A Systems Approach to Technology Education.

ERIC Educational Resources Information Center

Hacker, Michael; Barden, Robert

1983-01-01

Provides a brief history of industrial arts curriculum development, a rationale for a technology-based study of industrial arts, and the use of a systems view in understanding and interpreting technology. (SK)

Current report on the interferon program at Roswell Park Memorial Institute.

PubMed

Murphy, G P

1981-01-01

An overview of the interferon program at Roswell Park Memorial Institute (RPMI), is presented. This program encompasses three interrelated areas of research and new drug development: (a) basic research on purification and characterization of animal and human interferons (leukocyte, fibroblast, and immune); (b) large scale manufacture and preclinical testing of human fibroblast interferon (HFIF); and (c) clinical trials with HFIF to determine its safety of administration as well as antiviral, antitumor, and immunomodulatory activities in patients with neoplastic or viral disease. The antitumor effect of HFIF produced at RPMI as assessed by intralesional injection of various metastatic nodules resulted in an overall 71% local response. Phase I studies in 13 patients demonstrated that HFIF can be administered safely by the subcutaneous, intramuscular, and intravenous routes in doses up to 25 million units per day without any serious untoward effects. Intrathecal administration of HFIF into patients with CNS leukemia was also well tolerated. Pharmacokinetic studies indicated significant levels of HFIF in serum and cerebrospinal fluid after intravenous and intrathecal administration, respectively. Coincidental with the HFIF systemic administration during the Phase I trials, favorable responses in several laboratory, immune, and clinical parameters were observed. These results provide the rationale for conducting phase II and phase III clinical trials with HFIF produced at RPMI.

30-days mortality in patients with perforated peptic ulcer: A national audit

PubMed Central

Nakano, Anne; Bendix, Jørgen; Adamsen, Sven; Buck, Daniel; Mainz, Jan; Bartels, Paul; Nørgård, Bente

2008-01-01

Background In 2005, The Danish National Indicator Project (DNIP) reported findings on patients hospitalized with perforated ulcer. The indicator “30-days mortality” showed major discrepancy between the observed mortality of 28% and the chosen standard (10%). Rationale An audit committee was appointed to examine quality problems linked to the high mortality. The purpose was to (i) examine patient characteristics, (ii) evaluate the appropriateness of the standard, and (iii) audit all cases of deaths within 30 days after surgery. Methods Four hundred and twelve consecutive patients were included and used for the analyses of patient characteristics. The evaluation of the standard was based on a literature review, and a structured audit was performed according to the 115 deaths that occurred. Results The mean age was 69.1 years, 42.0% had one co-morbid disease and 17.7% had two co-morbid diseases. 45.9% had an American Association of Anaesthetists score of 3–4. We found no results on mortality in studies similar to ours. The audit process indicated that the postoperative observation of patients was insufficient. Discussion As a result of this study, the standard for mortality was increased to 20%, and the new indicators for postoperative monitoring were developed. The DNIP continues to evaluate if these initiatives will improve the results on mortality. PMID:22312201

Learning Rationales and Virtual Reality Technology in Education.

ERIC Educational Resources Information Center

Chiou, Guey-Fa

1995-01-01

Defines and describes virtual reality technology and differentiates between virtual learning environment, learning material, and learning tools. Links learning rationales to virtual reality technology to pave conceptual foundations for application of virtual reality technology education. Constructivism, case-based learning, problem-based learning,…

"ComPost": A Writing Program Newsletter and Its Rationale.

ERIC Educational Resources Information Center

Hall, Dennis R.

1993-01-01

Discusses the development and rationale of "ComPost," a weekly newsletter of the Composition Program at the University of Louisville. Suggests that a vehicle like ComPost can promote the communications that contribute to accomplishing collegiality and genuine program consensus. (RS)

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

PubMed

Noordman, Bo Jan; Wijnhoven, Bas P L; Lagarde, Sjoerd M; Boonstra, Jurjen J; Coene, Peter Paul L O; Dekker, Jan Willem T; Doukas, Michael; van der Gaast, Ate; Heisterkamp, Joos; Kouwenhoven, Ewout A; Nieuwenhuijzen, Grard A P; Pierie, Jean-Pierre E N; Rosman, Camiel; van Sandick, Johanna W; van der Sangen, Maurice J C; Sosef, Meindert N; Spaander, Manon C W; Valkema, Roelf; van der Zaag, Edwin S; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-02-06

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.

Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives

PubMed Central

Sparks, Jeffrey A.; Iversen, Maura D.; Kroouze, Rachel Miller; Mahmoud, Taysir G.; Triedman, Nellie A.; Kalia, Sarah S.; Atkinson, Michael L.; Lu, Bing; Deane, Kevin D.; Costenbader, Karen H.; Green, Robert C.; Karlson, Elizabeth W.

2014-01-01

We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. PMID:25151341

A Cluster-Randomized Trial of Restorative Practices: An Illustration to Spur High-Quality Research and Evaluation

PubMed Central

Acosta, Joie D.; Chinman, Matthew; Ebener, Patricia; Phillips, Andrea; Xenakis, Lea; Malone, Patrick S.

2017-01-01

Restorative Practices in schools lack rigorous evaluation studies. As an example of rigorous school-based research, this paper describes the first randomized control trial of restorative practices to date, the Study of Restorative Practices. It is a 5-year, cluster-randomized controlled trial (RCT) of the Restorative Practices Intervention (RPI) in 14 middle schools in Maine to assess whether RPI impacts both positive developmental outcomes and problem behaviors and whether the effects persist during the transition from middle to high school. The two-year RPI intervention began in the 2014–2015 school year. The study’s rationale and theoretical concerns are discussed along with methodological concerns including teacher professional development. The theoretical rationale and description of the methods from this study may be useful to others conducting rigorous research and evaluation in this area. PMID:28936104

Facing History and Ourselves: The Study of the Holocaust and Human Behavior

ERIC Educational Resources Information Center

Strom, Margot Stern

1978-01-01

Presents a rationale for teaching about the Nazi Holocaust and describes a unit of study for eighth graders that builds on concepts of conflict and conflict resolution, power, fairness and justice, leadership, decision making, and obedience. (KS)

Inhalation of Photochemically Altered Urban Mixtures Depresses Cardiac Function in Mice

EPA Science Inventory

Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled photochemical products in urban mixtures in a murine model. ...

Input-Based Approaches to Teaching Grammar: A Review of Classroom-Oriented Research.

ERIC Educational Resources Information Center

Ellis, Rod

1999-01-01

Examines the theoretical rationales (universal grammar, information-processing theories, skill-learning theories) for input-based grammar teaching and reviews classroom-oriented research (i.e., enriched-input studies, input-processing studies) that has integrated this option. (Author/VWL)

Development of Food Acceptance Patterns.

ERIC Educational Resources Information Center

Birch, Leann L.

1990-01-01

Provides a rationale for the significance of the study of early feeding and delineates major issues that require investigation. Includes a list of acquisition processes implicated in the development of food acceptance patterns. (RH)

Management, Ethics and the Military Chaplin.

DTIC Science & Technology

for the rationale that military chaplains should integrate these principles in their work. A practical approach toward the principles of management is suggested and the moral implications of their application is studied. (Author)

Cardiotoxic and Cardioprotective Features of Chronic β-adrenergic Signaling

PubMed Central

Zhang, Xiaoying; Szeto, Christopher; Gao, Erhe; Tang, Mingxin; Jin, Jianguo; Fu, Qin; Makarewich, Catherine; Ai, Xiaojie; Li, Ying; Tang, Allen; Wang, Jenny; Gao, Hui; Wang, Fang; Ge, Xinyi Joy; Kunapuli, Satya P.; Zhou, Lin; Zeng, Chunyu; Xiang, Kevin Yang; Chen, Xiongwen

2012-01-01

Rationale In the failing heart, persistent β-adrenergic receptor (βAR) activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium/calmodulin-dependent kinase II (CaMKII). β-Adrenergic signaling pathways are also capable of activating cardioprotective mechanisms. Objective This study used a novel PKA inhibitor peptide (PKI) to inhibit PKA activity to test the hypothesis that βAR signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways. Methods and Results In PKI transgenic mice, chronic isoproterenol (ISO) failed to induce cardiac hypertrophy, fibrosis, myocyte apoptosis and depressed cardiac function. In cultured adult feline ventricular myocytes (AFVMs), PKA inhibition protected myocytes from death induced by β1-AR agonists by preventing cytosolic and SR Ca2+ overload and CaMKII activation. PKA inhibition revealed a cardioprotective role of β-adrenergic signaling via cAMP/EPAC /Rap1/Rac/ERK pathway. Selective PKA inhibition causes protection in the heart after myocardial infarction (MI) that was superior to β-blocker therapy. Conclusion These results suggest that selective block of PKA could be a novel heart failure therapy. PMID:23104882

Differentiation and concordance in smallholder land use strategies in southern Mexico's conservation frontier.

PubMed

Roy Chowdhury, Rinku

2010-03-30

Forest cover transitions in the developing tropics are conditioned by agricultural change. The expansion, intensification, and diversification of agricultural land uses are tied to regional economic/environmental regimes and decisions of local farming households. Land change science and agrarian systems research share an interest in the drivers of household strategies, land use impacts, and typologies of those land uses/drivers. This study derives a typology of farming households in southern Mexico based on emergent patterns in their land use combinations and analyzes their household and policy drivers. The results reveal broadly diversified household land use portfolios as well as three emergent clusters of farmstead production orientation: (i) extensive subsistence-oriented conservationists, (ii), dual extensive-intensive farmers, and (iii) nonextensive diversified land users. Household membership in these clusters is uneven and strongly related to tenancy, land endowments, wage labor, and policy subsidies. Although most households are following a nonextensive agricultural strategy incorporating off-farm incomes, the likelihood of a regional forest transition remains debatable because of the disproportionate deforestation impacts of the less common strategies. Conservation development policies in the region need to accommodate diverse smallholder farming rationales, increase off-farm opportunities, and target sustainable development with the assistance of community conservation leaders.

Evaluating Adaptive Governance Approaches to Sustainable Water Management in North-West Thailand

NASA Astrophysics Data System (ADS)

Clark, Julian R. A.; Semmahasak, Chutiwalanch

2013-04-01

Adaptive governance is advanced as a potent means of addressing institutional fit of natural resource systems with prevailing modes of political-administrative management. Its advocates also argue that it enhances participatory and learning opportunities for stakeholders over time. Yet an increasing number of studies demonstrate real difficulties in implementing adaptive governance `solutions'. This paper builds on these debates by examining the introduction of adaptive governance to water management in Chiang Mai province, north-west Thailand. The paper considers, first, the limitations of current water governance modes at the provincial scale, and the rationale for implementation of an adaptive approach. The new approach is then critically examined, with its initial performance and likely future success evaluated by (i) analysis of water stakeholders' opinions of its first year of operation; and (ii) comparison of its governance attributes against recent empirical accounts of implementation difficulty and failure of adaptive governance of natural resource management more generally. The analysis confirms the potentially significant role that the new approach can play in brokering and resolving the underlying differences in stakeholder representation and knowledge construction at the heart of the prevailing water governance modes in north-west Thailand.

Interplay between Reaction and Phase Behaviour in Carbon Dioxide Hydrogenation to Methanol.

PubMed

Reymond, Helena; Amado-Blanco, Victor; Lauper, Andreas; Rudolf von Rohr, Philipp

2017-03-22

Condensation promotes CO 2 hydrogenation to CH 3 OH beyond equilibrium through in situ product separation. Although primordial for catalyst and reactor design, triggering conditions as well as the impact on sub-equilibrium reaction behaviour remain unclear. Herein we used an in-house designed micro-view-cell to gain chemical and physical insights into reaction and phase behaviour under high-pressure conditions over a commercial Cu/ZnO/Al 2 O 3 catalyst. Raman microscopy and video monitoring, combined with online gas chromatography analysis, allowed the complete characterisation of the reaction bulk up to 450 bar (1 bar=0.1 MPa) and 350 °C. Dew points of typical effluent streams related to a parametric study suggest that the improving reaction performance and reverting selectivities observed from 230 °C strongly correlate with (i) a regime transition from kinetic to thermodynamic, and (ii) a phase transition from a single supercritical to a biphasic reaction mixture. Our results advance a rationale behind transitioning CH 3 OH selectivities for an improved understanding of CO 2 hydrogenation under high pressure. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Infantile-onset Pompe disease with neonatal debut

PubMed Central

Martínez, Miriam; Romero, Mar García; Guereta, Luis García; Cabrera, Marta; Regojo, Rita M.; Albajara, Luis; Couce, Maria L.; de Pipaon, Miguel Saenz

2017-01-01

Abstract Rationale: Infantile-onset Pompe disease, also known as glycogen storage disease type II, is a progressive and fatal disorder without treatment. Enzyme replacement therapy with recombinant human acid alpha-glucosidase (GAA) enhances survival; however, the best outcomes have been achieved with early treatment. Patient concerns: We report a case of a newborn with infantile-onset Pompe disease diagnosed in the first days of life who did not undergo universal neonatal screening. The patient was asymptomatic, with a general physical examination revealing only a murmur. The clinical presentation was dominated by the neonatal detection of hypertrophic cardiomyopathy, without hypotonia or macroglossia. Diagnoses: Pompe disease was confirmed in the first week of life by GAA activity in dried blood spots, and a GAA genetic study showed the homozygous mutation p.Arg854X. Interventions: Parents initially refused replacement therapy. Outcomes: The patient experienced recurrent episodes of ventricular fibrillation during central line placement and could not be resuscitated. Lessons: Although Pompe disease is rare, and universal screening has not been established, neonatologists should be alerted to the diagnosis of Pompe in the presence of hypertrophic cardiomyopathy. Diagnosis is achieved in a few days with the aid of dried blood spots. PMID:29390460

Intercultural Sensitivity through Short-Term Study Abroad

ERIC Educational Resources Information Center

Bloom, Melanie; Miranda, Arturo

2015-01-01

One of the foremost-cited rationales for study abroad during college is the development of a global perspective and intercultural sensitivity. Although this argument is mentioned frequently in promotional materials for study abroad, it has not yet been backed by research based on the outcomes of students' study abroad experiences. As more…

38 CFR 1.15 - Standards for program evaluation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the data. (f) Each program evaluation requires a systematic research design to collect the data necessary to measure the objectives. This research design should conform to the following: (1) Rationale. The research design for each evaluation should contain a specific rationale and should be structured...

Overview: MINNEMAST.

ERIC Educational Resources Information Center

Adams, Patricia A., Ed.

This illustrated booklet provides a rationale and overview for the twenty-nine coordinated mathematics and science units in the MINNEMAST program for kindergarten through third grade. The rationale for the program cites both the historical association of mathematics and science and pedagogical advantages. The goals of the project are to provide…

Effect of Training on Reasoning in Moral Choice.

ERIC Educational Resources Information Center

Kaplan, Martin F.

Moral development is viewed as a matter of progression in the cognitive reasoning and rationale underlying choices and judgments. Traditionally, retrospective reports of rationales have been used to measure moral development levels, resulting in unreliable information. Information Integration Theory attempts to assess individual differences in…

Knowledge in the Postmodern University.

ERIC Educational Resources Information Center

Simpson, Evan

2000-01-01

It is essential for higher education to interpret its institutional goals. This essay facilitates that task by clarifying the intellectual rationale of the postmodern challenge, highlighting the success of that rationale, and arguing that the interrelated critiques of rationalism, realism, and foundationalism show that the modern university…

Celebrating Censored Books.

ERIC Educational Resources Information Center

Karolides, Nicholas J., Ed.; Burress, Lee, Ed.

Intended to provide rationales for the use of a group of controversial books in American public schools, this manual explains the educational values of 33 of the most frequently challenged books. Detailed rationales include such information as historical perspective, literary elements, pertinence, and thematic content. Some of the titles include…

Rationale and design of a study using a standardized locally procured macronutrient supplement as adjunctive therapy to HIV treatment in Kenya.

PubMed

Sztam, Kevin A; Ndirangu, Murugi; Sheriff, Muhsin; Arpadi, Stephen M; Hawken, Mark; Rashid, Juma; Deckelbaum, Richard J; El Sadr, Wafaa M

2013-01-01

Poor nutritional status at initiation of antiretroviral therapy (ART) is predictive of mortality. Decreased dietary intake is a major determinant of weight loss in HIV. Despite a biological rationale to treat undernutrition in adults receiving ART, few studies have provided data on feasibility, safety, effectiveness, and sustainability of specific macronutrient supplements with HIV treatment in adults, especially supplements such as a food basket, a supplement approach seldom evaluated in spite of its wide use. We present the rationale and design for a study of a locally procured macronutrient supplement given to HIV-infected patients initiating ART with a body mass index (BMI) ≤20.0 kg/m(2). The objective was to determine feasibility of procurement, distribution, safety and to obtain preliminary effectiveness data for a locally procured supplement. The design was a comparative study for 200 adult participants at two Kenya government-supported clinics. The primary outcome was BMI at 24 weeks. Supplement duration was 24 weeks, total follow-up was 48 weeks, and the study included a comparison site. Novel aspects of this study include use of a standardized macronutrient supplement to protect the participant against household food sharing, and a complementary micronutrient supplement. Comprehensive data collected included dietary intake, HIV-related quality-of-life, food security, neuropsychiatric assessments, laboratory studies, and household geomapping. Assessments were made at baseline, at 24 weeks, and at 48 weeks post-ART initiation. Challenges included establishing a partnership with local millers, distribution from the HIV clinic, food safety, and tracking of participants. These findings will help inform nutrition support programming in Kenya and similar settings, and provide needed data regarding use of macronutrient supplements as an adjunctive intervention with ART.

North Carolina Social Studies Curriculum 1997.

ERIC Educational Resources Information Center

North Carolina State Dept. of Public Instruction, Raleigh.

This North Carolina curriculum guide provides a social studies framework for grades K-12. Divided into overview, introduction, primary, elementary/middle, and high school sections, the guide outlines a purpose and philosophy, framework goals, rationale for social studies in the curriculum, content overview (for the disciplines of history,…

Seventh Grade Interdisciplinary Packet (Science-Social Studies).

ERIC Educational Resources Information Center

Madison Public Schools, WI. Dept. of Curriculum Development.

GRADES OR AGES: Grade 7. SUBJECT MATTER: Science and Social Studies. ORGANIZATION AND PHYSICAL APPEARANCE: This guide presents a series of earth sciences units which would have interdisciplinary potential specifically in the area of social studies. Introductory material includes a rationale, evaluation procedures, 44 "key" environmental concepts,…

Why History? Thinking about the Uses of the Past.

ERIC Educational Resources Information Center

Stricker, Frank

1992-01-01

Discusses reasons for studying history. Suggests that compelling arguments for historical study will affect students' attitudes throughout life. Evaluates common rationales for studying history. Includes history as fun, tradition, great ideas, human folly, escapism, and nationalist legitimation. Urges that students be taught history as facts that…

The Mediterranean healthy eating, ageing, and lifestyle (MEAL) study: rationale and study design.

PubMed

Grosso, Giuseppe; Marventano, Stefano; D'Urso, Maurizio; Mistretta, Antonio; Galvano, Fabio

2017-08-01

There is accumulating evidence suggesting that Mediterranean lifestyles, including nutrition and sleeping patterns as well as social integration, may play a role in reducing age-related diseases. However, the literature is mostly deficient of evidence provided by Italian Mediterranean islands that more closely adhered to the originally described lifestyles. In this paper, we described the rationale and the study design of the Mediterranean healthy Eating, Ageing, and Lifestyle (MEAL) study, a prospective population-based cohort established in Sicily, southern Italy. The main exposures investigated are classical determinants of health, including demographic, nutritional habits, smoking and physical activity status, as well as eating-related behaviors, sleeping habits, sun exposure, social resources, and perceived stress. Anthropometric measurements will be collected. The main outcomes included depression, quality of life, and, after the follow-up period, also cardiovascular disease and cancer. The MEAL study may provide important data to increase our knowledge regarding the prevalence, incidence, and risk factors of age-related disorders in the Mediterranean region.

Pilot study: incorporation of pharmacogenetic testing in medication therapy management services.

PubMed

Haga, Susanne B; Allen LaPointe, Nancy M; Moaddeb, Jivan; Mills, Rachel; Patel, Mahesh; Kraus, William E

2014-11-01

Aim: To describe the rationale and design of a pilot study evaluating the integration of pharmacogenetic (PGx) testing into pharmacist-delivered medication therapy management (MTM). Study rationale: Clinical delivery approaches of PGx testing involving pharmacists may overcome barriers of limited physician knowledge about and experience with testing. Study design: We will assess the addition of PGx testing to MTM services for cardiology patients taking three or more medications including simvastatin or clopidogrel. We will measure the impact of MTM plus PGx testing on drug/dose adjustment and clinical outcomes. Factors associated with delivery, such as time to prepare and conduct MTM and consult with physicians will be recorded. Additionally, patient interest and satisfaction will be measured. Anticipated results: We anticipate that PGx testing can be practically integrated into standard a MTM service, providing a viable delivery model for testing. Conclusion: Given the lack of evidence of an effective PGx delivery models, this study will provide preliminary evidence regarding a pharmacist-delivered approach.

Urban Ecology: Exploring Wildlife in the City.

ERIC Educational Resources Information Center

Malcarne, Vanessa

1982-01-01

Provides rationale for and examples of nature study activities using school yards, vacant lots, and city parks. Focusing on city wildlife, the interdisciplinary activities provide experiences in observing and investigating. Three duplicating masters (animals on ground, animals overhead, and tree study) are provided. (JN)

Discrimination and Integration in the Foundations of Education.

ERIC Educational Resources Information Center

Lawson, Robert F.

This paper reviews the basis and organizational rationale for Foundations of Education courses. Instructional objectives for Foundations courses are included. The unity and effectiveness of Foundations fields are studied in light of the viability of integrated work and study in the Foundations. (MJM)

Fish oil and olive oil-rich diets modify ozone-induced cardiovascular effect in rats

EPA Science Inventory

Rationale: Air pollution exposure has been associated with adverse cardiovascular health effects. Our clinical studies suggest that fish oil (FO) and olive oil (OO) supplementations attenuate the cardiovascular responses to inhaled concentrated ambient particles. This study was...

A New Competitive Edge. Volunteers from the Workplace.

ERIC Educational Resources Information Center

Vizza, Cynthia; And Others

This book provides information on workplace volunteering and how employee volunteering programs operate in specific corporate cultures. Chapter 1 focuses on the rationale upon which corporate volunteer programs are constructed. The rationale's four basic components are discussed in detail: quality of life, worker participation, responding to…

Invitation to the Birthday Party: Rationale and Description

ERIC Educational Resources Information Center

Ginsburg, Herbert P.; Pappas, Sandra

2016-01-01

Educators in many countries around the world have a strong interest in improving early childhood mathematics education, one component of which is formative assessment. Unlike summative assessment, this approach can provide teachers with information useful for understanding and teaching individual children. This paper describes the rationale for…

Stanton's "The Solitude of Self": A Rationale for Feminism.

ERIC Educational Resources Information Center

Campbell, Karlyn Kohrs

1980-01-01

Examines Elizabeth Cady Stanton's speech, "The Solitude of Self," as a philosophical statement of the principles underlying the nineteenth century struggle for woman's rights in the United States. Analyzes the lyric structure and tone of the speech and its tragic, existential rationale for feminism. (JMF)

Strength Training. Rationale for Current Guidelines for Adult Fitness Programs.

ERIC Educational Resources Information Center

Feigenbaum, Matthew S.; Pollock, Michael L.

1997-01-01

Strength training is an effective method of developing musculoskeletal strength and is often prescribed for fitness, health, and for prevention and rehabilitation of orthopedic injuries. This paper describes and presents a rationale for the population-specific strength training guidelines established by major health organizations. (SM)

Calcasieu Parish Spark Program for Primary Gifted/Talented Students: Guidelines and Curriculum. Revised.

ERIC Educational Resources Information Center

Bankens, Barbara; Hillebrandt, Marlene

Presented is the curriculum guide for primary grade gifted and talented students in Calcasieu Parish, Louisiana. Introductory information includes information on program philosophy, rationale, definition of giftedness, goals of the program, identifying characteristics of giftedness, identification and placement, rationale for curriculum…

The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

PubMed Central

Tiano, Luca; Silvestri, Sonia; Orlando, Patrik; Calcabrini, Cinzia; Stocchi, Vilberto

2017-01-01

Sarcopenia represents an increasing public health risk due to the rapid aging of the world's population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS) production and decreased antioxidant (AO) defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed. PMID:29123615

Telework rationale and implementation for people with disabilities: considerations for employer policymaking.

PubMed

Moon, Nathan W; Linden, Maureen A; Bricout, John C; Baker, Paul M A

2014-01-01

Telework has been promoted as a viable workplace accommodation for people with disabilities since the 1990s, when information and communication technologies (ICT) had developed sufficiently to facilitate its widespread adoption. This initial research and accompanying policy recommendations were prescriptive in nature and frequently aimed at employers. This article adds to existing policy models for facilitating successful telework outcomes for people with disabilities. Drawing upon two studies by the Rehabilitation Engineering Research Center on Workplace Accommodations, we expound on employee-side considerations in the implementation of telework. Our policy model utilizes established typologies for policy evaluation to develop a process model that considers rationales and implementation factors for telework among people with physical disabilities. Telework may be used as an accommodation for disability, but employee rationales for telework are more complex, involving work-life balance, strategies for pain and fatigue not formally recognized as disability, and expediency in travel and transportation. Implementation of telework as a component of workplace operations is similarly multifaceted, involving non-technology accommodations to realize job restructuring left incomplete by telework. Our model grounds new empirical research in this area. We also renew our call for additional research on effective telework practices for people with disabilities.

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

PubMed Central

Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-01-01

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. Purpose We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. Methods This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Results Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. Potential limitations Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. Conclusions The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products. PMID:22058086

The rehabilitation of attention in patients with mild cognitive impairment and brain subcortical vascular changes using the Attention Process Training-II. The RehAtt Study: rationale, design and methodology.

PubMed

Salvadori, Emilia; Poggesi, Anna; Valenti, Raffaella; Della Rocca, Eleonora; Diciotti, Stefano; Mascalchi, Mario; Inzitari, Domenico; Pantoni, Leonardo

2016-10-01

Cerebral small vessel disease (SVD) may cause attentional and executive cognitive deficits. No drug is currently available to improve cognitive performance or to prevent dementia in SVD patients, and cognitive rehabilitation could be a promising approach. We aimed to investigate: (1) the effectiveness of the Attention Process Training-II program in the rehabilitation of patients with mild cognitive impairment (MCI) and SVD; (2) the impact of the induced cognitive improvement on functionality and quality of life; (3) the effect of training on brain activity at rest and the possibility of a training-induced plasticity effect. The RehAtt study is designed as a 3-year prospective, single-blinded, randomized clinical trial. Inclusion criteria were: (1) MCI defined according to Winblad et al. criteria; (2) evidence of impairment across attention neuropsychological tests; (3) evidence on MRI of moderate/severe white matter hyperintensities. All enrolled patients are evaluated at baseline, and after 6 and 12 months, according to an extensive clinical, functional, MRI and neuropsychological protocol. The baseline RehAtt cohort includes 44 patients (66 % males, mean ± SD age and years of education 75.3 ± 6.8 and 8.3 ± 4.3, respectively). After baseline assessment, patients have been randomly assigned to 'attention training' or 'standard care'. Treatments and follow-up visits at 6 months are completed, while follow-up visits at 12 months are ongoing. This study is the first attempt to reduce attention deficits in patients affected by MCI with SVD. The results of this pilot experience will represent an essential background for designing larger multicenter, prospective, double-blinded, randomized and controlled clinical trials. NCT02033850 (ClinicalTrials.gov Identifier).

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C.

PubMed

Reddy, K Rajender; Belle, Steven H; Fried, Michael W; Afdhal, Nezam; Navarro, Victor J; Hawke, Roy L; Wahed, Abdus S; Doo, Edward; Meyers, Catherine M

2012-02-01

Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products.

Adapting clinical guidelines in low‐resources countries: a study on the guideline on the management and prevention of type 2 diabetes mellitus in Indonesia

PubMed Central

Wangge, Grace; van der Graaf, Yolanda; van der Heijden, Geert J. M. G.

2016-01-01

Abstract Rationale, aims and objectives Most of the clinical guidelines in low‐resource countries are adaptations from preexisting international guidelines. This adaptation can be problematic when those international guidelines are not based on current evidence or original evidence‐based international guidelines are not followed. This study aims to evaluate the quality of an Indonesian type 2 diabetes mellitus guideline adapted from selected international guidelines. Methods The “Consensus on the Management and Prevention of type 2 Diabetes in Indonesia 2011” is a guideline by the Indonesian Society of Endocrinology (Perkeni). Four parent guidelines identified from its list of references were from the International Diabetes Federation (IDF), American Association of Clinical Endocrinologist (AACE), American Diabetes Association (ADA), and one jointly released by ADA and European Association for the Study of Diabetes (EASD). Two reviewers independently assessed its quality using the Appraisal of Guidelines, Research and Evaluation Collaboration (AGREE II) instrument. Six recommendations were compared: (1) screening for diabetes; (2) diagnosis; (3) control of hyperglycemia; (4) target blood glucose; (5) target blood pressure; and (6) treatment of dyslipidemia. Results Perkeni's guideline satisfied 55% of the AGREE II items, while its parent guidelines satisfied 59% to 74%. Perkeni's shows low score on “rigor of development” and “applicability” and the lowest score in the “scope and purpose” domain. Differences were found in 4 recommendations: the screening of diabetes, control of hyperglycemia, target blood glucose, and treatment of dyslipidemia. In 3 of 4, Perkeni followed the ADA's recommendation. Conclusion Derivation of recommendations from parent guidelines and their adaptation to the context of Indonesian health care lacks transparency. When guidelines are either derived from other guidelines or adapted for use in different context, evidence‐based practice principles should be followed and adhered to. PMID:27592587

Making Their Own Path: Preservice Teachers' Development of Purpose in Social Studies Teacher Education

ERIC Educational Resources Information Center

Hawley, Todd S.; Crowe, Alicia R.

2016-01-01

Despite a solid body of research on rationale development in social studies teacher education, little research exists exploring how social studies preservice teachers' purposes develop over time. This article presents four examples of social studies preservice teachers as they grappled with developing a purpose for teaching social studies.…

Epistemology in Qualitative Educational Research: A Review of Published Articles

ERIC Educational Resources Information Center

Ulum, Ömer Gökhan

2016-01-01

This study explores the epistemological basis for qualitative educational research studies. Within this context, 20 qualitative studies on education were analysed and three dimensions were sorted out: (1) the purpose or aim of the study, (2) the rationale for the study, and (3) the occurrence of epistemological aspects (theory, paradigm,…

Costing Educational Wastage: A Pilot Simulation Study. Current Surveys and Research in Statistics.

ERIC Educational Resources Information Center

Berstecher, D.

This pilot simulation study examines the important methodological problems involved in costing educational wastage, focusing specifically on the cost implications of educational wastage in primary education. Purpose of the study is to provide a clearer picture of the underlying rationale and interrelated consequences of reducing educational…

Omega-3 Fatty Acid Attenuates Cardiovascular Effects in Healthy Older Volunteers Exposed to Concentrated Ambient Fine and UltrafineParticulate Matter

EPA Science Inventory

Rationale: Ambient particulate matter (PM) exposure has been associated with adverse cardiovascular effects. A recent epidemiology study reported that omega-3 polyunsaturated fatty acid (fish oil) supplementation blunted the response of study participants to PM. Our study was des...

A Study of Motivational Influences on Academic Achievement

ERIC Educational Resources Information Center

Dishon-Berkovits, Miriam

2014-01-01

This study examined the influence of motivation on academic achievement. The theoretical rationale for the study is grounded in bridging two influential yet isolated literatures of motivation: goal setting theory and achievement goal theory. Although it is clear that academic performance should be influenced by assigned learning goals,…

One Size Fits All? Slow Cortical Potentials Neurofeedback: A Review

ERIC Educational Resources Information Center

Mayer, Kerstin; Wyckoff, Sarah N.; Strehl, Ute

2013-01-01

Objective: The intent of this manuscript was to review all published studies on slow cortical potentials (SCP) neurofeedback for the treatment of ADHD, with emphasis on neurophysiological rationale, study design, protocol, outcomes, and limitations. Method: For review, PubMed, MEDLINE, ERIC, and Google Scholar searches identified six studies and…

Authenticating Historical Fiction: Rationale and Process

ERIC Educational Resources Information Center

Groce, Eric; Groce, Robin

2005-01-01

In merging social studies education with language arts, classroom teachers are utilizing selections of historical fiction to teach critical literacy skills while also meeting social studies standards. While most of the selections used for teaching history and social studies themes are strong in terms of literary merit, they may be deficient in…

A Field Guide for Sign Language Research.

ERIC Educational Resources Information Center

Stokoe, William; Kuschel, Rolf

Field researchers of sign language are the target of this methodological guide. The prospective researcher is briefed on the rationale of sign language study as language study and as distinct from the study of kinesics. Subjects covered include problems of translating, use of interpreters, and ethics. Instruments for obtaining social and language…

Social Studies Curriculum Guidelines.

ERIC Educational Resources Information Center

Manson, Gary; And Others

These guidelines, which set standards for social studies programs K-12, can be used to update existing programs or may serve as a baseline for further innovation. The first section, "A Basic Rationale for Social Studies Education," identifies the theoretical assumptions basic to the guidelines as knowledge, thinking, valuing, social participation,…

Internationalisation of Higher Education in South Africa: A Historical Review

ERIC Educational Resources Information Center

Sehoole, Chika

2006-01-01

Current debates on internationalisation are couched in relation to globalisation, and gives the impression that this phenomenon is new. There is also a tendency to discuss internationalisation in relation to various rationales, with economic rationales being dominant. This article challenges the assumption that internationalisation is something…

Writing a Rationale for a Controversial Common Reading Book: Alice Walker's "The Color Purple."

ERIC Educational Resources Information Center

Worthington, Pepper

1985-01-01

Offers a rationale that can be used to defend the assignment of Alice Walker's controversial novel for class reading. Indicates four issues that might evoke calls for censorship: (1) subject matter, (2) vocabulary, (3) grammar, and (4) the epistolary form of the work. (RBW)

The Landscape of the Liberal Arts

ERIC Educational Resources Information Center

Roche, Mark W.

2013-01-01

This chapter provides a rationale for the value of a liberal arts education, addressing briefly the recent history of the liberal arts, explaining the value of the liberal arts in diverse educational settings as opposed to simply residential liberal arts colleges, and exploring a contemporary rationale for the liberal arts.

Rationale for Incorporating Health and Safety into the Curriculum.

ERIC Educational Resources Information Center

Fleischman, Marvin

1988-01-01

Presents a philosophical commentary on the need and rationale for incorporating safety and health into the chemical engineering curriculum. Proposes safety and health assessments as useful teaching methods. Describes an approach to bringing safety and health into undergraduate engineering curricula. Gives examples of integration of these curricula…

Use and Rationale of Media Types in Performance-Centered Design.

ERIC Educational Resources Information Center

Schubert, Dave

2002-01-01

Focuses on the convergent rationale and use of media within performance centered design and how that can affect user performance using real-time electronic performance support system appliance design. Discusses the more effective time-based, interactive, and synchronized media types that have become viable with technological advancements.…

Coercion or Compulsion?: Rationales behind Informal Payments for Education in Azerbaijan

ERIC Educational Resources Information Center

Lepisto, Eric; Kazimzade, Elmina

2009-01-01

Although informal payments are necessary for education systems in many countries, they prohibit education accessibility and equity in Eastern Europe and neighboring states. Exploring the rationales and the relationships is a promising approach for understanding corruption in education and ensuring educational equity. In this article, rationales…

AIDS Education--What Should We Be Evaluating?

ERIC Educational Resources Information Center

Slattery, Monica

A rationale for determining what evaluations of AIDS education programs should assess is outlined. The rationale is based in: educational theory with a distinction made between knowing and understanding and an emphasis on helping learners understand the concepts being taught; and teacher development literature and theories, with assessment of…

Dance: A Guide to Curriculum Development in the Arts.

ERIC Educational Resources Information Center

Iowa State Dept. of Public Instruction, Des Moines.

The purpose of this guide is to present dance education as a discipline and to encourage student participation in a wide range of dance activities. The unit, "Rationale/Philosophy/Goals," contains an introduction to the program, a rationale, and overall goals. "Scope/Sequence/Strategies," presents a chart which lists basic…

Rationale of Early Adopters of Fossil Fuel Divestment

ERIC Educational Resources Information Center

Beer, Christopher Todd

2016-01-01

Purpose: This research uses the social science perspectives of institutions, ecological modernization and social movements to analyze the rationale used by the early-adopting universities of fossil fuel divestment in the USA. Design/methodology/approach: Through analysis of qualitative data from interviews with key actors at the universities that…

Social Stories[TM]: A Possible Theoretical Rationale

ERIC Educational Resources Information Center

Reynhout, Georgina; Carter, Mark

2011-01-01

Social Stories[TM] are an intervention widely used with individuals with autism spectrum disorders (ASD). This paper discusses a possible theoretical rationale that might account for the purported efficacy of Social Stories[TM]. Attributes of individuals with ASD in relation to Social Story intervention including difficulties with theory of mind…

Building "Applied Linguistic Historiography": Rationale, Scope, and Methods

ERIC Educational Resources Information Center

Smith, Richard

2016-01-01

In this article I argue for the establishment of "Applied Linguistic Historiography" (ALH), that is, a new domain of enquiry within applied linguistics involving a rigorous, scholarly, and self-reflexive approach to historical research. Considering issues of rationale, scope, and methods in turn, I provide reasons why ALH is needed and…

Achieving Balance: Secondary Physical Education Gender-Grouping Options

ERIC Educational Resources Information Center

Gabbei, Ritchie

2004-01-01

This article provides options and a rationale for expanding gender-grouping considerations to include single-gender, coed, and combination strategies for instruction in secondary physical education classes. This rationale is based on empirical evidence that suggests that female students are denied equal opportunity to achieve learning goals during…

Logistic Approximation to the Normal: The KL Rationale

ERIC Educational Resources Information Center

Savalei, Victoria

2006-01-01

A rationale is proposed for approximating the normal distribution with a logistic distribution using a scaling constant based on minimizing the Kullback-Leibler (KL) information, that is, the expected amount of information available in a sample to distinguish between two competing distributions using a likelihood ratio (LR) test, assuming one of…

Oral Health Promotion in Schools: Rationale and Evaluation

ERIC Educational Resources Information Center

Kizito, Alex; Caitlin, Meredith; Wang, Yili; Kasangaki, Arabat; Macnab, Andrew J.

2014-01-01

Purpose: The purpose of this paper is to explain the rationale and potential for the WHO health promoting schools (HPS) to improve children's oral health, and describe validated quantitative methodologies and qualitative approaches to measure program impact. Design/Methodology/Approach: Critical discussion of the impact of poor oral health and…

Legitimizing Technical Communication in English Departments: Carolyn Miller's "Humanistic Rationale for Technical Writing"

ERIC Educational Resources Information Center

Moore, Patrick

2006-01-01

Carolyn Miller's oft-cited "Humanistic Rationale for Technical Writing," published in 1979, tries to give technical communication faculty more cultural capital in English departments controlled by literature professors. Miller replaces a positivistic emphasis in technical communication pedagogy with rhetoric. She shows how technical knowledge is…

Talent Search: Purposes, Rationale, and Role in Gifted Education.

ERIC Educational Resources Information Center

Olszewski-Kubilius, Paula

1998-01-01

This paper describes the purpose and rationale of a "talent search" effort to identify gifted students through use of off-level testing. Three components are stressed: diagnosis and evaluation of domains and levels of talent; educational placement and guidance; and talent development opportunities. Research supporting the talent-search…

77 FR 41147 - Endangered and Threatened Wildlife and Plants; Designation of Revised Critical Habitat for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-12

... segments and associated flycatcher habitat are anticipated to support the strategy, rationale, and science... strategy, rationale, and science of flycatcher conservation in order to meet territory and habitat-related... costs associated with monitoring and education activities, fencing, habitat restoration and creation...

A Rationale for Outdoor Activity as Experiential Education: The Reason for Freezin'.

ERIC Educational Resources Information Center

Kesselheim, A. Donn

John Dewey said, "Learning is thinking about experience". This dictum accurately reflects the rationale for outdoor activity as experiential education. The term "outdoor learning" refers to a set of activities which have the following characteristics in common: environmental contrast (a sharp environmental change for the participant); physical…

The Case for Consequences for Academic Dishonesty

ERIC Educational Resources Information Center

Kiviniemi, Marc T.

2015-01-01

This paper discusses the rationale of implementing an "academic dishonesty equals F policy." The author asserts that faculty must take seriously those things which students are expected to take seriously. Integrity--academic, personal, and professional--is worth taking seriously. He goes on to provide three rationales to justify this…

STEM Education: Proceed with Caution

ERIC Educational Resources Information Center

Williams, P. John

2011-01-01

The STEM (science, technology, engineering and mathematics) movement has developed from a non-educational rationale. Although some think it may enliven the delivery of maths and science in classrooms, the social and economic rationales are those that have initiated this movement. Spurred on by the global financial crisis, it is hoped that…

Outdoor Education for the Whole Child.

ERIC Educational Resources Information Center

Staley, Frederick A.

Focusing on outdoor education in a broad sense, this book comprehensively provides elementary school teachers with rationale, planning guidance, and specific ideas for using the outdoors to enhance the development of the whole child through the stimulation of both right and left hemispheres of the brain. Part I presents a definition, rationale,…

Practical Lessons To Promote a Global Perspective in Elementary Education.

ERIC Educational Resources Information Center

Jarchow, Elaine, Ed.; Midkiff, Ronald, Ed.; Pickert, Sarah, Ed.

This book for elementary school teachers presents a rationale for developing a global perspective, providing sample lesson plans and a curriculum resource guide. Chapter 1, "Promoting a Global Perspective in Elementary Education" (Ronald G. Midkiff), uses stories from one teacher's global experiences to offer a rationale for promoting…

Construction engineering inspection direct cost survey.

DOT National Transportation Integrated Search

2014-07-01

The objective of the study was to provide a rationale to Georgia Department of Transportation : (GDOT) for Direct Costs in terms of salary and wages charged by qualified independent : contractors performing Construction Engineering Inspection (CEI) s...

The Empirical Basis for Adopting a Civic Rationale for Internationalization

ERIC Educational Resources Information Center

Horn, Aaron S.; Hendel, Darwin D.; Fry, Gerald W.

2012-01-01

While considerable consensus exists regarding the importance of internationalizing postsecondary education, little is known about whether distinct forms of internationalization influence civic engagement. This study estimates the degree to which study abroad and internationalization at home (IaH) are associated with international volunteerism…

Integrating Classical Music into the Elementary Social Studies Curriculum.

ERIC Educational Resources Information Center

Bracken, Khlare R.

1997-01-01

Provides a rationale for using classical music as the basis of interdisciplinary units in elementary social studies. Recommends beginning with a series of humorous pieces to familiarize students with classical music. Includes many examples for utilizing pieces related to geography and history. (MJP)

Proposal to the National Science Foundation for a retrospective technology assessment of submarine telegraphy

NASA Technical Reports Server (NTRS)

Coates, V. T.; Finn, B. S.

1975-01-01

The conceptual and methodological importance of doing retrospective technology assessments is summarized. The rationale for the study of submarine telegraphy is briefly summarized along with the study plan, the management plan, and dissemination and utilization of the results.

Industrial Exposures at Birth are Associated with Reduced Forced Vital Capacity in Childhood

EPA Science Inventory

Rationale: Previous studies have reported associations of ambient air pollutant exposures with childhood decrements in lung volumes. While the current study was designed primarily to examine traffic exposures, we also examined the impact of other early life exposures on pulmonary...

Evaluation of the relationship of service levels, functional categories, and design standards for general aviation airports

DOT National Transportation Integrated Search

1999-08-01

This study examines certain airport design standards in an effort to understand the rationale behind their development. Researchers studied the standards to identify potential standards for relaxing. The focus is on smaller, less active airports wher...

RESPIRATORY DOSE TO SUSCEPTIBLE POPULATIONS ASSESSED BY EXPOSURE AND DOSIMETRY STUDIES

EPA Science Inventory

Respiratory Dose to Susceptible Populations Assessed by Exposure and Dosimetry Studies

Chong Kim1 and Ronald Williams2, 1USEPA National Health and Environmental Effects Research Laboratory and 2USEPA National Exposure Research Laboratory, RTP, NC.

Rationale: Parti...

Life's end: Ethnographic perspectives.

PubMed

Goodwin-Hawkins, Bryonny; Dawson, Andrew

2018-01-01

In this introduction to the special issue, Life's End: Ethnographic Perspectives, we review the field of anthropological studies of death and dying. We make the argument that, largely because of its sub-disciplining into the larger field of the anthropology of religion, ritual and symbolism, the focus of anthropological research on death has been predominantly on post- rather than pre-death events, on death's beginnings rather than life's ends. Additionally, we argue that an anthropological aversion to the study of dying may also lie in the intimacy of the discipline's principal method, ethnography. Contrastingly, we argue that this very methodological intimacy can be a source of insight, and we offer this as a rationale for the special issue as a whole, which comprises eight ethnographic studies of dying and social relations at life's end from across Africa, Australia, Europe, and North America. Each of these studies is then summarized, and a rationale for their presentation around the themes of "structures of dying," "care for the dying," "hope in dying," and "ending life" is presented.

Ethnicity and mental health: conceptualization, definition and operationalization of ethnicity from a Canadian context.

PubMed

Clarke, D E; Colantonio, A; Rhodes, A E; Escobar, M

2008-01-01

The current study provides a critical review of Canadian studies on ethnicity and mental health with respect to the definition, conceptualization and operationalization of ethnicity. It provides a discussion on the methodological issues related to these factors and their implications to guide future research and enable comparability of results across studies. Sociological Abstracts, PsycINFO, MEDLINE and CINAHL were used to identify relevant Canadian articles published between January 1980 and December 2004. The review highlights a number of key issues for future researchers to consider such as the need for: 1) clear rationales as to why ethnicity is important to their outcome of interest; 2) clarity on the definition of ethnicity, which affects its conceptualization and operationalization; 3) a theoretically driven conceptualization of ethnicity, which should be related to the research question of interest; and 4) clear rationales for the decisions made regarding the data source used, the operationalization of ethnicity, and the ethnic categories included in their studies.

Hanford waste-form release and sediment interaction: A status report with rationale and recommendations for additional studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serne, R.J.; Wood, M.I.

1990-05-01

This report documents the currently available geochemical data base for release and retardation for actual Hanford Site materials (wastes and/or sediments). The report also recommends specific laboratory tests and presents the rationale for the recommendations. The purpose of this document is threefold: to summarize currently available information, to provide a strategy for generating additional data, and to provide recommendations on specific data collection methods and tests matrices. This report outlines a data collection approach that relies on feedback from performance analyses to ascertain when adequate data have been collected. The data collection scheme emphasizes laboratory testing based on empiricism. 196more » refs., 4 figs., 36 tabs.« less

The Italian Consensus Conference on Pain in Neurorehabilitation: rationale and methodology

PubMed Central

Tamburin, Stefano; Paolucci, Stefano; Magrinelli, Francesca; Musicco, Massimo; Sandrini, Giorgio

2016-01-01

Pain is very common in the neurorehabilitation setting, where it may not only represent a target for treatment but can also negatively influence rehabilitation procedures directly or through the side effects of painkillers. To date, there are neither guidelines nor consensus on how to assess and treat pain in neurorehabilitation. Because of the very scanty pieces of evidence on this topic, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) was promoted under the auspices of different scientific societies. This article illustrates the rationale, methodology, and topics of the ICCPN. The recommendations of the ICCPN will offer some information on how to deal with pain in neurorehabilitation and may represent the starting point for further studies. PMID:27313474

Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives.

PubMed

Sparks, Jeffrey A; Iversen, Maura D; Miller Kroouze, Rachel; Mahmoud, Taysir G; Triedman, Nellie A; Kalia, Sarah S; Atkinson, Michael L; Lu, Bing; Deane, Kevin D; Costenbader, Karen H; Green, Robert C; Karlson, Elizabeth W

2014-09-01

We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation.

PubMed

Ferris, Robert L; Lenz, Heinz-Josef; Trotta, Anna Maria; García-Foncillas, Jesús; Schulten, Jeltje; Audhuy, François; Merlano, Marco; Milano, Gerard

2018-02-01

Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity-including, but not limited to, ADCC-provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Expansion of Early Childhood Development Services and the Need to Reconceptualize Evidence

ERIC Educational Resources Information Center

Nilsen, Ann Christin E.

2017-01-01

The provision of early childhood development services is expanding in developing countries. The rationale behind this expansion is rooted in developmental psychology, socio-economic and human rights narratives. However, there are some limitations to this rationale, which are in particular related to the implicit universalism it assumes. This…

The Contribution of Pragmatism to Understanding Educational Action Research: Value and Consequences

ERIC Educational Resources Information Center

Hammond, Michael

2013-01-01

This paper argues that action research finds a rationale in the pragmatic position that knowledge is provisional and generated through a transaction between agent and environment. Action research finds a further methodological rationale in the pragmatic view that knowledge is generated within indeterminate situations, requires habits of reflection…

Developing a Language Learning Rationale for African Language Tutorials.

ERIC Educational Resources Information Center

Dwyer, David

1999-01-01

Presents a rationale for the supervised tutorial component of the African language program at Michigan State University. The supervised tutorial is one of two modes through which African languages are offered at Michigan State University. The other, which is teacher led, is offered for high enrollment languages such as Arabic, Swahili, and Hausa.…

Introducing ICT in Schools in England: Rationale and Consequences

ERIC Educational Resources Information Center

Hammond, Michael

2014-01-01

This paper provides a critical perspective on the attempts to promote the use of information and communication technology (ICT) in teaching and learning in England. It describes the rationale given for the introduction of ICT in terms of its potential to impact on educational standards to contribute to developing a curriculum which has more…

The Theory of Higher Education

ERIC Educational Resources Information Center

Brubacher, John S.

1970-01-01

Discusses two current theories of the university -- one that it is an agency detached from the social milieu that provides a rationale for teaching and research, the other that it is caught in the stresses and strains of contemporary events and provides a rationale for teaching, research, and public service. Adapted from paper presented at meeting…

Subsidizing Early Childhood Education and Care for Parents on Low Income: Moving beyond the Individualized Economic Rationale of Neoliberalism

ERIC Educational Resources Information Center

Simpson, Donald; Envy, Rose

2015-01-01

Neoliberalism and an associated "new politics of parenting" adopts a predominantly economic rationale which discursively positions early childhood education and care (ECEC) as essential to tackling several social ills by allowing individual parents (particularly young mothers) to improve their labour force participation, thus boosting…

Rationale for Students Preparation and Entrepreneurship Education in the Face of Global Economic Crisis in Nigeria

ERIC Educational Resources Information Center

Onuma, Nwite

2016-01-01

The rationale for students preparation in job creation through entrepreneurship education was examined. Problems of unemployment among Nigerian university graduates and challenges to entrepreneurship in the face of global economic crisis were also highlighted. The persistent problem of unemployment among University graduates and its attendant…

International Student Recruitment to Universities in England: Discourse, Rationales and Globalisation

ERIC Educational Resources Information Center

Bolsmann, Chris; Miller, Henry

2008-01-01

The recruitment of international students to universities in England has become a central issue in an era of globalisation for university administrators, senior managers, international offices and heads of schools and faculties. We examine the policy rationales for the recruitment of international students to England. Through the use of in-depth…

Developing Pre-Technical Secondary Education Programs: Rationale, Content, and Methodology.

ERIC Educational Resources Information Center

Georgia State Univ., Atlanta. Dept. of Vocational and Career Development.

This guide outlines the rationale, content, and methodology of a three-part high technology program that was developed in Georgia to provide secondary school students with training in the areas of electronics and electromechanical and mechanical technologies. Discussed first are the Georgia Initiative, the impact of high technology and the role of…

Market Failures and the Rationale for National Parks.

ERIC Educational Resources Information Center

Turner, Robert W.

2002-01-01

Discusses how market failures can, in principle, be used to justify national parks. States the best rationale is based on existence or nonuse values instead of the recreational aspects. Shows more evidence (costs of providing and operating the parks and the magnitude of nonuse values) is needed before the case becomes compelling. (JEH)

"Citizen Jane": Rethinking Design Principles for Closing the Gender Gap in Computing.

ERIC Educational Resources Information Center

Raphael, Chad

This paper identifies three rationales in the relevant literature for closing the gender gap in computing: economic, cultural and political. Each rationale implies a different set of indicators of present inequalities, disparate goals for creating equality, and distinct principles for software and web site design that aims to help girls overcome…

Photography and the Visible Arts.

ERIC Educational Resources Information Center

Barley, Steven D.

Six basic rationales for teaching art must be fused together if we are to reach the objective of helping non-artists achieve sensitivity in reacting to and acting upon their environment. The historical rationale reasons that if we can see the importance of art in previous cultures, we must transmit that importance in our culture by educating…

Descriptors for Law-Related Education.

ERIC Educational Resources Information Center

Wisconsin State Dept. of Public Instruction, Madison.

This guide provides a framework for developing a law-related curriculum in grades K-12. It is presented in nine major sections. Section I discusses the rationale for including law-related education in the curriculum. The rationale is that in order for citizens to make conscious choices, they must understand legal processes, reason through the need…

Rationale for the Cultural Construction of School Mental Health Programming

ERIC Educational Resources Information Center

Arora, Prerna G.; Nastasi, Bonnie K.; Leff, Stephen S.

2017-01-01

The implementation of evidence-based psychological programming to meet the needs of a global population has been impeded by the translation of theories and research findings across populations and settings without due consideration of cultural factors. The purpose of this article is to discuss the rationale for use of partnership-based methods in…

Ethnicity and British Colonialism; The Rationale for Racially-Based Schools

ERIC Educational Resources Information Center

Whitehead, Clive

2005-01-01

This paper examines the rationale for ethnic schooling in former British colonial territories in East Africa and Southeast Asia. Critics, especially of British rule in Malaya and Singapore, have traditionally claimed that ethnic schools were established as part of a British political strategy of "divide et impera". An examination the…

Integrating the Beliefs of Dewey, Lewin, and Rogers into a Rationale for Effective Group Leadership.

ERIC Educational Resources Information Center

Grove, Richard W.

1992-01-01

Presents a rationale for effective group leadership grounded in John Withall's articulation of selected beliefs of John Dewey, Kurt Lewin, and Carl Rogers. Teachers and administrators need more and better preparation in collaborative inquiry. Knowledge and skills in collaborative inquiry should undergird the successful functioning of groups of…

Laryngeal High-Speed Videoendoscopy: Rationale and Recommendation for Accurate and Consistent Terminology

ERIC Educational Resources Information Center

Deliyski, Dimitar D.; Hillman, Robert E.; Mehta, Daryush D.

2015-01-01

Purpose: The authors discuss the rationale behind the term "laryngeal high-speed videoendoscopy" to describe the application of high-speed endoscopic imaging techniques to the visualization of vocal fold vibration. Method: Commentary on the advantages of using accurate and consistent terminology in the field of voice research is…

Interdisciplinarity in United States Schools: Past, Present, and Future

ERIC Educational Resources Information Center

Boix Mansilla, Veronica; Lenoir, Yves

2010-01-01

This article examines the historical evolution of the concepts of interdisciplinarity and integration in American education. We first focus on United States education in the 20th century to review the rationales for integrated and interdisciplinary primary and secondary education. We place such rationales in the context of the larger purposes…

Roles and Structures for Participation in Higher Education Governance: A Rationale.

ERIC Educational Resources Information Center

Ikenberry, Stanley O.

It is obvious that the roles for participation of faculty, students and administrators in campus governance are inadequately defined and that the organizational structure through which these roles might be performed is deficient. This paper considers the rationale for such faculty and student organizations and examines some issues that have to be…

Glycogen Synthase Kinase 3 Protein Kinase Activity Is Frequently Elevated in Human Non-Small Cell Lung Carcinoma and Supports Tumour Cell Proliferation

PubMed Central

O′Flaherty, Linda; Pardo, Olivier E.; Dzien, Piotr; Phillips, Lois; Morgan, Carys; Pawade, Joya; May, Margaret T.; Sohail, Muhammad; Hetzel, Martin R.; Seckl, Michael J.; Tavaré, Jeremy M.

2014-01-01

Background Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including in non-small cell lung carcinoma (NSCLC). We examined the undefined role of GSK3 protein kinase activity in tissue from human NSCLC. Methods The expression and protein kinase activity of GSK3 was determined in 29 fresh frozen samples of human NSCLC and patient-matched normal lung tissue by quantitative immunoassay and western blotting for the phosphorylation of three distinct GSK3 substrates in situ (glycogen synthase, RelA and CRMP-2). The proliferation and sensitivity to the small-molecule GSK3 inhibitor; CHIR99021, of NSCLC cell lines (Hcc193, H1975, PC9 and A549) and non-neoplastic type II pneumocytes was further assessed in adherent culture. Results Expression and protein kinase activity of GSK3 was elevated in 41% of human NSCLC samples when compared to patient-matched control tissue. Phosphorylation of GSK3α/β at the inhibitory S21/9 residue was a poor biomarker for activity in tumour samples. The GSK3 inhibitor, CHIR99021 dose-dependently reduced the proliferation of three NSCLC cell lines yet was ineffective against type II pneumocytes. Conclusion NSCLC tumours with elevated GSK3 protein kinase activity may have evolved dependence on the kinase for sustained growth. Our results provide further important rationale for exploring the use of GSK3 inhibitors in treating NSCLC. PMID:25486534

Psychological factors affect the frequency of belching in patients with aerophagia.

PubMed

Bredenoord, Albert J; Weusten, Bas L A M; Timmer, Robin; Smout, André J P M

2006-12-01

In patients with aerophagia and excessive belching an organic cause is seldom found and a psychogenic cause is often suspected. To investigate the effects of attention and distraction on the frequency of belching in patients with aerophagia. In 10 patients with aerophagia, combined esophageal manometry and impedance monitoring was performed for 2 h, consisting of four 30-minute recording periods. Period I: patient unaware that recording had commenced. Period II: patient informed of recording in progress. Period III: distraction by filling in questionnaires. Period IV: no distraction. A total of 1,258 belches was measured, 51 of which were the result of air that escaped from the stomach (gastric belches). A total of 1,207 belches (96%) were events during which air was expelled in the oral direction almost immediately after entering the esophagus from there (supragastric belches). Gastric belches were distributed equally over the first (1.5 [0.5-2.0]), second (1.5 [0.5-2.0]), third (1.0 [0-2.0]), and fourth (1.0 [0-2.0]) recording periods. In contrast, the incidence of supragastric belches increased significantly from 0 (0-32) in period I to 30 (18-60) in period II, after patients were told that recording was started. During period III (questionnaires) the incidence of supragastric belches decreased to 14 (4-30). In period IV the incidence of supragastric belches increased to 21 (10-49). When patients with excessive belching are unaware that they are being studied or when they are distracted, the incidence of belching is significantly reduced. These findings underline the importance of psychological factors and provide rationale for behavioral therapy.

Individual Differences in Initial Sensitivity and Acute Tolerance Predict Patterns of Chronic Drug Tolerance to Nitrous-Oxide-Induced Hypothermia in Rats

PubMed Central

Ramsay, Douglas S.; Kaiyala, Karl J.; Leroux, Brian G.; Woods, Stephen C.

2006-01-01

Rationale: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations. Objectives: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops. Methods: During an initial 3-h administration of 60% nitrous oxide (N2O), male Long-Evans rats were screened for N2O’s hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N2O or placebo gas. Core temperature was measured telemetrically. Results: Rats that exhibited a comparable degree of hypothermia during an initial N2O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N2O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N2O exposure, the II group breathing N2O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N2O exposures. Conclusions: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent adaptive responses may mediate this relationship. PMID:15778887

SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR

PubMed Central

Tiziano, Francesco Danilo; Pinto, Anna Maria; Fiori, Stefania; Lomastro, Rosa; Messina, Sonia; Bruno, Claudio; Pini, Antonella; Pane, Marika; D'Amico, Adele; Ghezzo, Alessandro; Bertini, Enrico; Mercuri, Eugenio; Neri, Giovanni; Brahe, Christina

2010-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Three forms of SMA are recognized (type I–III) on the basis of clinical severity. All patients have at least one or more (usually 2–4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7. Recently, evidence has been provided that SMN2 expression can be enhanced by pharmacological treatment. However, no reliable biomarkers are available to test the molecular efficacy of the treatments. At present, the only potential biomarker is the dosage of SMN products in peripheral blood. However, the demonstration that SMN full-length (SMN-fl) transcript levels are reduced in leukocytes of patients compared with controls remains elusive (except for type I). We have developed a novel assay based on absolute real-time PCR, which allows the quantification of SMN1-fl/SMN2-fl transcripts. For the first time, we have shown that SMN-fl levels are reduced in leukocytes of type II–III patients compared with controls. We also found that transcript levels are related to clinical severity as in type III patients SMN2-fl levels are significantly higher compared with type II and directly correlated with functional ability in type II patients and with age of onset in type III patients. Moreover, in haploidentical siblings with discordant phenotype, the less severely affected individuals showed significantly higher transcript levels. Our study shows that SMN2-fl dosage in leukocytes can be considered a reliable biomarker and can provide the rationale for SMN dosage in clinical trials. PMID:19603064

Achieving Technological Literacy in Minnesota.

ERIC Educational Resources Information Center

Lindstrom, Mike

2002-01-01

Describes how Minnesota implemented the Standards for Technological Literacy: Content for the Study of Technology. Includes the timeline, rationale, potential activities and estimated costs associated with all phases, and steps for implementing the plan: investigate, replicate, integrate, and mandate. (JOW)

OXIDATIVE DNA DAMAGE IN DIESEL BUS MECHANICS

EPA Science Inventory

Rationale:

Diesel exposure has been associated with adverse health effects, including susceptibility to asthma, allergy and cancer. Previous epidemiological studies demonstrated increased cancer incidence among workers exposed to diesel. This is likely due to oxid...

Introduction: Why Teach about the Holocaust?

ERIC Educational Resources Information Center

Freedman, Theodore

1978-01-01

Presents a rationale for teaching about the Nazi era in social studies courses. Major objectives are to eliminate prejudice against Jews by rendering it intellectually indefensible and to help students deal with blind obedience to authority. (Author/DB)

Assertiveness Training and Christian Values.

ERIC Educational Resources Information Center

Bolsinger, Scot A.; McMinn, Mark R.

1989-01-01

Studies exploring the relationship between religious values and assertiveness are reviewed. Ideological obstacles in assertion training with religious clients are considered, and appropriate therapeutic strategies suggested. Emphasizes importance of presenting rationale for treatment and understanding client's value system. (Author/TE)

CARDIOVASCULAR EFFECTS OF ULTRAFINE CARBON PARTICLES IN HYPERTENSIVE RATS (SHR)

EPA Science Inventory

Rationale: Epidemiological evidence suggests that ultrafine particles are associated with adverse cardiovascular effects, specifically in elderly individuals with preexisting cardiovascular disease. The objective of this study was (i) to assess cardiopulmonary responses in adult ...

Plant Study Guide.

ERIC Educational Resources Information Center

Brynildson, Inga

Appropriate for secondary school botany instruction, this study guide focuses on the important roles of plants in human lives. Following a rationale for learning the basic skills of a botanist, separate sections discuss the process sunlight undergoes during photosynthesis, the flow of energy in the food chain, alternative plant lifestyles, plant…

Kids in Germany: Comparing Students from Different Cultures.

ERIC Educational Resources Information Center

Fitzhugh, William P.

This unit of study, intended for intermediate grade students, focuses on comparing students from different cultures: Germany and the United States. The unit addresses National Social Studies Standards (NCSS) standards; presents an introduction, such as purpose/rationale; cites a recommended grade level; states objectives; provides a time…

Interdisciplinary Invigoration of Creativity Studies

ERIC Educational Resources Information Center

Ambrose, Don

2017-01-01

The forces of globalization are magnifying the importance of interdisciplinary creative work. While the field of creativity studies always has been more open to interdisciplinary idea borrowing than many other fields, it can and should do more interdisciplinary synthesizing. This article begins with a discussion of the rationale for encouraging…

Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

PubMed Central

Broekman, Winifred; Khedoe, Padmini P S J; Schepers, Koen; Roelofs, Helene; Stolk, Jan; Hiemstra, Pieter S

2018-01-01

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research. PMID:29653970

Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

PubMed Central

Grosmaire, Anne Gaëlle; Battini, Elena

2017-01-01

A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections), modulate neural activity (noninvasive brain stimulation), and enhance motivation (virtual reality) in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them. PMID:29057269

Does the addition of visceral manipulation improve outcomes for patients with low back pain? Rationale and study protocol.

PubMed

Panagopoulos, John; Hancock, Mark; Ferreira, Paulo

2013-07-01

There has been no randomised controlled trial conducted to investigate the effectiveness of visceral manipulation (VM) for the treatment of low back pain (LBP). The primary aim of this study would be to investigate whether the addition of VM, to a standard physiotherapy treatment regimen, improves pain 6 weeks post treatment commencement in people with LBP. Secondary aims would be to examine the effect of VM on disability and functional outcomes at 2, 6 and 52 weeks post-treatment commencement and pain at 2 and 52 weeks. This paper describes the rationale and design of a randomised controlled trial investigating the addition of VM to a standard physiotherapy treatment algorithm which includes manual therapy, specific exercise and functional exercise prescription. Analysis of data would be carried out by a statistician blinded to group allocation and by intention-to-treat. Copyright © 2013 Elsevier Ltd. All rights reserved.

Renal insufficiency following contrast media administration trial II (REMEDIAL II): RenalGuard system in high-risk patients for contrast-induced acute kidney injury: rationale and design.

PubMed

Briguori, Carlo; Visconti, Gabriella; Ricciardelli, Bruno; Condorelli, Gerolama

2011-04-01

The combined prophylactic strategy of sodium bicarbonate plus N-acetylsyteine (NAC) seems to be effective in preventing contrast induced acute kidney injury (CI-AKI) in patients at low-to-medium risk. However, in patients at high and very high risk the rate of CI-AKI is still high. In this subset of patients the anticipated advantages of the RenalGuard(tm) System should be investigated. The RenalGuard(tm) System (PLC Medical Systems, Inc., Franklin, MA, USA) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard therapy, which is based on the theory that creating and maintaining a high urine output is beneficial by allowing a quick elimination of contrast media, and, therefore, reducing its toxic effects. The REMEDIAL II trial is a randomised, multicentre, investigator-sponsored trial addressing the hypothesis that the RenalGuard System is superior to the prophylaxis with sodium bicarbonate infusion plus NAC in preventing CI-AKI in high and very high risk patients. Consecutive patients with chronic kidney disease (CKD) and at high to very high risk for CI-AKI, referred to our institutions for coronary and/or peripheral procedures, will be randomly assigned to 1) prophylactic administration of sodium bicarbonate plus NAC (control group) and 2) RenalGuard System treatment (RenalGuard group). All enrolled patients must have an estimated glomerular filtration rate ≤ 30 ml/min/1.73 m2 and/or a contrast nephropathy risk score ≥ 11. In all cases iodixanol (an iso-osmolar, non-ionic contrast agent) will be administered. The primary endpoint is an increase of ≥ 0.3 mg/dL in the serum creatinine concentration 48 hours after the procedure. The REMEDIAL II trial will give important answers on how to prevent CI-AKI in high and very high risk patients undergoing contrast media exposure.

Toddler Techies: A Study of Young Children's Interaction with Computers

ERIC Educational Resources Information Center

Ellis, Kirsten; Blashki, Kathy

2004-01-01

This article describes an ethnographic study of children's behavioural interaction with multimedia within a familiar context. The rationale for such a study was to provide data and evaluation of the capabilities of young children in an expressly modified multimedia environment and to determine the usefulness of employing technology as an adjunct…

Social Studies: A Guide for Curriculum Development.

ERIC Educational Resources Information Center

Indiana State Dept. of Public Instruction, Indianapolis.

This social studies curriculum guide is designed for grades K-12. Divided into seven sections, the first section offers a brief introduction and calls attention to the laws and rulings in Indiana which affect the teaching of social studies. Section two outlines the guide's rationale which stresses that knowledge must be combined with rational…

Teaching Canada for the '80s. Curriculum Series, 35.

ERIC Educational Resources Information Center

Hodgetts, A. B.; Gallagher, Paul

A rationale for Canadian studies and outlines of appropriate content for various grade levels are presented. The book is designed to help teachers, curriculum planners, and teacher educators in preparing effective Canadian studies programs. Chapter I offers a discussion of the need for pan-Canadian understanding. Canadian studies can help young…

Craft Knowledge: Of Disciplinarity in Writing Studies

ERIC Educational Resources Information Center

Johnson, Robert R.

2010-01-01

This article argues that craft knowledge can provide a disciplinary rationale for writing studies. It draws from the ancient concepts of teche, phronesis, and the four causes of making and makes the case for a definition of disciplinary knowledge fitting for writing studies. The article concludes with a conceptual framework that can serve as a…

Arts-Based Learning and Leadership Development: A Case Study

ERIC Educational Resources Information Center

Brenner, Michael Yoel

2010-01-01

This qualitative case study was designed to explore how participants in an arts-based leadership development program learned to draw on their right brain capabilities in order to develop the creative competencies required to solve complex modern-day problems in new and different ways. The rationale for this study emerges from the researcher's…

Complexity Thinking and Methodology: The Potential of "Complex Case Study" for Educational Research

ERIC Educational Resources Information Center

Hetherington, Lindsay

2013-01-01

Complexity theories have in common perspectives that challenge linear methodologies and views of causality. In educational research, relatively little has been written explicitly exploring their implications for educational research methodology in general and case study in particular. In this paper, I offer a rationale for case study as a research…

A randomized study of dietary composition during weight-loss maintenance: Rationale, study design, intervention, and assessment

USDA-ARS?s Scientific Manuscript database

While many people with overweight or obesity can lose weight temporarily, most have difficulty maintaining weight loss over the long term. Studies of dietary composition typically focus on weight loss, rather than weight-loss maintenance, and rely on nutrition education and dietary counseling, rathe...

The Composing Process: A Critical Review of Some Recent Studies.

ERIC Educational Resources Information Center

Crismore, Avon

Six of the 10 existing research studies that attempt to characterize the composing process by examining certain components and behaviors are critically reviewed in this paper. For each study, the aims and data gathering and sampling procedures are described, and the findings, interpretations, design, and rationale of the research are critically…

A Study of Aboriginal Teachers' Professional Knowledge and Experience in Canadian Schools

ERIC Educational Resources Information Center

St. Denis, Verna

2010-01-01

This qualitative study, initiated by the Canadian Teachers' Federation and its Advisory Committee on Aboriginal Education, explored the professional knowledge and experiences of Aboriginal (First Nations, Mets and Inuit) teachers. The rationale for the study was to address the urgent need to improve and promote Aboriginal education in public…

Student Mobility Reviewed: Attraction and Satisfaction of International Students in Turkey

ERIC Educational Resources Information Center

Kondakci, Yasar

2011-01-01

Building on international migration theories and the literature on the dynamics of student mobility, this study sketches a two-dimensional framework and examines its utility to understand the rationales of in-bounding student mobility in Turkey. The empirical part of the study was conducted with 331 international students studying in public…

Alabama Course of Study: Social Studies K-12. Bulletin 1980, No. 22. Revised.

ERIC Educational Resources Information Center

Alabama State Dept. of Education, Montgomery.

This guide presents in four sections a course of study in social studies for use in Alabama for grades K-12. Section one includes a rationale for teaching social studies; a listing of management, methods, and content characteristics of a good social studies program; and an extensive list of social studies objectives. Some objectives of the program…

Facilitating Children's Self-Concept: A Rationale and Evaluative Study

ERIC Educational Resources Information Center

Hay, Ian

2005-01-01

This study reports on the design and effectiveness of the Exploring Self-Concept program for primary school children using self-concept as the outcome measure. The program aims to provide a procedure that incorporates organisation, elaboration, thinking, and problem-solving strategies and links these to children's multidimensional self-concept.…

Low energy stage study. Volume 5: Program study cost elements and appendices. [orbital launching of space shuttle payloads

NASA Technical Reports Server (NTRS)

1978-01-01

The methodology and rationale used in the development of costs for engineering, manufacturing, testing and operating a low thrust system for placing automated shuttle payloads into earth orbits are described. Cost related information for the recommended propulsion approach is included.

A Study of the Inter-Organizational Behavior in Consortia. Final Report.

ERIC Educational Resources Information Center

Silverman, Robert J.

In an attempt to formulate hypotheses and administrative guidelines for voluntary consortia in higher education, a heuristic framework was devised through which behavioral patterns of consortia member organizations and their representatives could be ascertained. The rationale, the framework, and the methodology of the study are first discussed.…

Is Tutoring Teaching? Exploring Tutoring's Potential to Improve Mathematics Teacher Education

ERIC Educational Resources Information Center

Rasche, Alexander N.

2017-01-01

This study investigated the tutoring practices of mathematics tutors working in one university tutoring center and the corresponding rationale exhibited by the mathematics tutors. This study illustrates how the tutoring practices of mathematics tutors align with the Eight Mathematics Teaching Practices outlined in NCTM's recent publication…

Moral Education in Canadian Social Studies: A Modest Proposal

ERIC Educational Resources Information Center

Cochrane, Don; Williams, David

1977-01-01

Recent ideas and publications concerning values and moral education have had little impact on social studies teaching in Canada. The article provides eight suggestions for improving values education, including leadership from provincial ministers of education, development of a values education rationale, and improvement of teacher education and…

Adolescent Attitudes towards Virtual Learning

ERIC Educational Resources Information Center

Pleau, Andrea R.

2012-01-01

This study was designed to examine adolescents' attitudes towards virtual schooling. Virtual schooling may be defined as any public or private organization that delivers instruction via the Internet. The rationale for this study is based on the increased number of adolescents opting to complete some or all of their secondary education through…

Overall Rationale and Design of Study.

ERIC Educational Resources Information Center

Hegsted, D. Mark

This paper outlines research designed to establish dietary correlates of malnutrition, and questions the common assumption that high protein foods should be used as dietary supplements in humans. Because thorough investigation of dietary needs in children is ethically unfeasible, squirrel monkeys were used in the research to study the biological…

Rationale, design and methods of the HEALTHY study physical education intervention component

USDA-ARS?s Scientific Manuscript database

The HEALTHY primary prevention trial was designed to reduce risk factors for type 2 diabetes in middle school students. Middle schools at seven centers across the United States participated in the 3-year study. Half of them were randomized to receive a multi-component intervention. The intervention ...

Reduced forced vital capacity in childhood associated with exposures to petroleum-related compounds at birth residence

EPA Science Inventory

Rationale: Previous studies have reported associations of ambient air pollutant exposures with childhood decrements in lung volumes. While the current study was designed primarily to examine traffic exposures, we also examined the impact of other early life exposures on pulmonary...

What We Do: A Multiple Case Study from Mathematics Coaches' Perspectives

ERIC Educational Resources Information Center

Kane, Barbara Ann

2013-01-01

Teachers face new challenges when they teach a more rigorous mathematics curriculum than one to which they are accustomed. The rationale for this particular study originated from watching teachers struggle with understanding mathematical content and pedagogical practices. Mathematics coaches can address teachers' concerns through sustained,…

The Effects of Marijuana on Human Cognition.

ERIC Educational Resources Information Center

Pearl, Joseph H.

Investigating the effects of marijuana on human psychological functioning, this study differs from previous research in two ways: 1) it is concerned with relatively complex cognitive processes; 2) it has a theoretical rationale. The general hypothesis of the study states that marijuana will impair its user's ability to form and use abstract…