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Sample records for address specific clinical

  1. Public Address Systems. Specifications - Installation - Operation.

    ERIC Educational Resources Information Center

    Palmer, Fred M.

    Provisions for public address in new construction of campus buildings (specifications, installations, and operation of public address systems), are discussed in non-technical terms. Consideration is given to microphones, amplifiers, loudspeakers and the placement and operation of various different combinations. (FS)

  2. Addressing the Mathematics-Specific Needs of Beginning Mathematics Teachers

    ERIC Educational Resources Information Center

    Britton, Edward

    2012-01-01

    Beginning mathematics teachers at the secondary level (middle and high school grades) have mathematics-specific needs that induction programs should address more substantially. However, a number of issues in how programs can accomplish this are more complex than often framed in discussions occurring in the induction programs and the field of…

  3. Addressing the needs of traumatic brain injury with clinical proteomics

    PubMed Central

    2014-01-01

    Background Neurotrauma or injuries to the central nervous system (CNS) are a serious public health problem worldwide. Approximately 75% of all traumatic brain injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of concussion injury today is limited to an assessment of behavioral symptoms, often with delay and subject to motivation. Hence, there is an urgent need for an accurate chemical measure in biofluids to serve as a diagnostic tool for invisible brain wounds, to monitor severe patient trajectories, and to predict survival chances. Although a number of neurotrauma marker candidates have been reported, the broad spectrum of TBI limits the significance of small cohort studies. Specificity and sensitivity issues compound the development of a conclusive diagnostic assay, especially for concussion patients. Thus, the neurotrauma field currently has no diagnostic biofluid test in clinical use. Content We discuss the challenges of discovering new and validating identified neurotrauma marker candidates using proteomics-based strategies, including targeting, selection strategies and the application of mass spectrometry (MS) technologies and their potential impact to the neurotrauma field. Summary Many studies use TBI marker candidates based on literature reports, yet progress in genomics and proteomics have started to provide neurotrauma protein profiles. Choosing meaningful marker candidates from such ‘long lists’ is still pending, as only few can be taken through the process of preclinical verification and large scale translational validation. Quantitative mass spectrometry targeting specific molecules rather than random sampling of the whole proteome, e.g., multiple reaction monitoring (MRM), offers an efficient and effective means to multiplex the measurement of several candidates in patient samples, thereby omitting the need for antibodies prior to clinical assay design. Sample preparation challenges specific to TBI are addressed. A

  4. Republished: Respiratory microbiota: addressing clinical questions, informing clinical practice

    PubMed Central

    Rogers, Geraint B; Shaw, Dominick; Marsh, Robyn L; Carroll, Mary P; Serisier, David J; Bruce, Kenneth D

    2015-01-01

    Over the last decade, technological advances have revolutionised efforts to understand the role played by microbes in airways disease. With the application of ever more sophisticated techniques, the literature has become increasingly inaccessible to the non-specialist reader, potentially hampering the translation of these gains into improvements in patient care. In this article, we set out the key principles underpinning microbiota research in respiratory contexts and provide practical guidance on how best such studies can be designed, executed and interpreted. We examine how an understanding of the respiratory microbiota both challenges fundamental assumptions and provides novel clinical insights into lung disease, and we set out a number of important targets for ongoing research. PMID:26304986

  5. Utilizing Motivational Interviewing to Address Resistant Behaviors in Clinical Supervision

    ERIC Educational Resources Information Center

    Wahesh, Edward

    2016-01-01

    Motivational interviewing is presented as an approach to address resistant behaviors in clinical supervision. A case example is used to illustrate the process in which the relational and technical elements of motivational interviewing can be applied to supervisee resistance. Implications for supervisors and researchers are discussed.

  6. Clinical strategies for addressing muscle weakness following knee injury.

    PubMed

    Pietrosimone, Brian; Blackburn, J Troy; Harkey, Matthew S; Luc, Brittney A; Pamukoff, Derek N; Hart, Joe M

    2015-04-01

    Muscle strength is a determinate of physical function and increasing muscle strength is an important clinical goal for patients with knee injury. This article discusses the emerging evidence regarding a novel rehabilitation strategy that uses disinhibitory modalities to increase neuromuscular activation in conjunction with traditional muscle strengthening for the purpose of maximizing strength gains following acute knee injury or surgery and in patients with knee osteoarthritis. The use of disinhibitory modalities and specific types of neuromuscular training for clinically maximizing strength are discussed.

  7. Beyond Values Clarification: Addressing Client Values in Clinical Behavior Analysis

    PubMed Central

    Bonow, Jordan T; Follette, William C

    2009-01-01

    Ethical principles of psychology, as exemplified in the American Psychological Association (APA) Code of Ethics (2002), provide impractical advice for addressing client values during psychotherapy. These principles seem to argue that each client's values should be respected and protected at all times, except in cases in which this would result in harm to the client or the general public. Although the code is appropriately designed as a defense against potential and actual abuses of professional power, this general proscription against directly targeting client values for change is based on an understanding of values that grants them special ontological status and has resulted in limited clinical interventions focusing solely on “values clarification.” With its strong foundation in a unified philosophical system, clinical behavior analysis offers a sophisticated alternative approach to values that both defines what they are and identifies when they can be ethically targeted to improve the lives of clients. PMID:22478514

  8. Addressing electronic clinical information in the construction of quality measures.

    PubMed

    Bailey, L Charles; Mistry, Kamila B; Tinoco, Aldo; Earls, Marian; Rallins, Marjorie C; Hanley, Kendra; Christensen, Keri; Jones, Meredith; Woods, Donna

    2014-01-01

    Electronic health records (EHR) and registries play a central role in health care and provide access to detailed clinical information at the individual, institutional, and population level. Use of these data for clinical quality/performance improvement and cost management has been a focus of policy initiatives over the past decade. The Children's Health Insurance Program Reauthorization Act of 2009 (CHIPRA)-mandated Pediatric Quality Measurement Program supports development and testing of quality measures for children on the basis of electronic clinical information, including de novo measures and respecification of existing measures designed for other data sources. Drawing on the experience of Centers of Excellence, we review both structural and pragmatic considerations in e-measurement. The presence of primary observations in EHR-derived data make it possible to measure outcomes in ways that are difficult with administrative data alone. However, relevant information may be located in narrative text, making it difficult to interpret. EHR systems are collecting more discrete data, but the structure, semantics, and adoption of data elements vary across vendors and sites. EHR systems also differ in ability to incorporate pediatric concepts such as variable dosing and growth percentiles. This variability complicates quality measurement, as do limitations in established measure formats, such as the Quality Data Model, to e-measurement. Addressing these challenges will require investment by vendors, researchers, and clinicians alike in developing better pediatric content for standard terminologies and data models, encouraging wider adoption of technical standards that support reliable quality measurement, better harmonizing data collection with clinical work flow in EHRs, and better understanding the behavior and potential of e-measures.

  9. Identifying and addressing specific student difficulties in advanced thermal physics

    NASA Astrophysics Data System (ADS)

    Smith, Trevor I.

    As part of an ongoing multi-university research study on student understanding of concepts in thermal physics at the upper division, I identified several student difficulties with topics related to heat engines (especially the Carnot cycle), as well as difficulties related to the Boltzmann factor. In an effort to address these difficulties, I developed two guided-inquiry worksheet activities (a.k.a. tutorials) for use in advanced undergraduate thermal physics courses. Both tutorials seek to improve student understanding of the utility and physical background of a particular mathematical expression. One tutorial focuses on a derivation of Carnot's theorem regarding the limit on thermodynamic efficiency, starting from the Second Law of Thermodynamics. The other tutorial helps students gain an appreciation for the origin of the Boltzmann factor and when it is applicable; focusing on the physical justification of its mathematical derivation, with emphasis on the connections between probability, multiplicity, entropy, and energy. Student understanding of the use and physical implications of Carnot's theorem and the Boltzmann factor was assessed using written surveys both before and after tutorial instruction within the advanced thermal physics courses at the University of Maine and at other institutions. Classroom tutorial sessions at the University of Maine were videotaped to allow in-depth scrutiny of student successes and failures following tutorial prompts. I also interviewed students on various topics related to the Boltzmann factor to gain a more complete picture of their understanding and inform tutorial revisions. Results from several implementations of my tutorials at the University of Maine indicate that students did not have a robust understanding of these physical principles after lectures alone, and that they gain a better understanding of relevant topics after tutorial instruction; Fisher's exact tests yield statistically significant improvement at the

  10. Addressing the clinical needs of problem drug user patients

    PubMed Central

    Krupski, Antoinette; West, Imara I.; Graves, Meredith C.; Atkins, David C.; Maynard, Charles; Bumgardner, Kristin; Donovan, Dennis; Ries, Richard; Roy-Byrne, Peter

    2016-01-01

    Introduction Illicit drug use is a serious public health problem associated with significant co-occurring medical disorders, mental disorders, and social problems. Yet most individuals with drug use disorders have never been treated, though they often seek medical treatment in primary care. The purpose of the present study was to examine baseline characteristics of persons presenting in primary care across a range of problem drug use severity to identify their clinical needs. Methods We examined socio-demographic characteristics, medical and psychiatric comorbidities, drug use severity, social and legal problems, and service utilization for 868 patients with drug problems recruited from primary care clinics in a safety-net medical setting. Based on Drug Abuse Screening Test (DAST-10) results, individuals were categorized as having low, intermediate, or substantial/severe drug use severity. Results Patients with substantial/severe drug use severity had serious drug use (opiates, stimulants, sedatives, intravenous drug use), high levels of homelessness (50%), psychiatric comorbidity (69%), arrests for serious crimes (24%), and frequent use of expensive emergency department and inpatient hospitals. Patients with low drug use severity were primarily users of marijuana with little reported use of other drugs, less psychiatric co-morbidity, and more stable lifestyles. Patients with intermediate drug use severity fell in-between the substantial/severe and low drug use severity subgroups on most variables. Conclusions Patients with highest drug use severity are likely to require specialized psychiatric and substance abuse care in addition to ongoing medical care that is equipped to address the consequences of severe/substantial drug use including intravenous drug use. Because of their milder symptoms, patients with low drug use severity may benefit from a collaborative care model that integrates psychiatric and substance abuse care in the primary care setting. Patients

  11. Beyond Values Clarification: Addressing Client Values in Clinical Behavior Analysis

    ERIC Educational Resources Information Center

    Bonow, Jordan T.; Follette, William C.

    2009-01-01

    Ethical principles of psychology, as exemplified in the American Psychological Association (APA) Code of Ethics (2002), provide impractical advice for addressing client values during psychotherapy. These principles seem to argue that each client's values should be respected and protected at all times, except in cases in which this would result in…

  12. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Addresses for submittal of plans, specifications, and calculations. 107.317 Section 107.317 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses...

  13. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Addresses for submittal of plans, specifications, and calculations. 107.317 Section 107.317 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses...

  14. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Addresses for submittal of plans, specifications, and calculations. 107.317 Section 107.317 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses...

  15. Addressing Low Literacy and Health Literacy in Clinical Oncology Practice

    PubMed Central

    Garcia, Sofia F.; Hahn, Elizabeth A.; Jacobs, Elizabeth A.

    2011-01-01

    Low functional literacy and low health literacy continue to be under-recognized and are associated with poorer patient health outcomes. Health literacy is a dynamic state influenced by how well a healthcare system delivers information and services that match patients’ abilities, needs and preferences. Oncology care poses considerable health literacy demands on patients who are expected to process high stakes information about complex multidisciplinary treatment over lengths of time. Much of the information provided to patients in clinical care and research is beyond their literacy levels. In this paper, we provide an overview of currently available guidelines and resources to improve how the needs of patients with diverse literacy skills are met by cancer care providers and clinics. We present recommendations for health literacy assessment in clinical practice and ways to enhance the usability of health information and services by improving written materials and verbal communication, incorporating multimedia and culturally appropriate approaches, and promoting health literacy in cancer care settings. The paper also includes a list of additional resources that can be used to develop and implement health literacy initiatives in cancer care clinics. PMID:20464884

  16. Current Issues Concerning Clinical Optometric Education. Keynote Address.

    ERIC Educational Resources Information Center

    Imperato, Pascal James

    1996-01-01

    Clinical optometric education is in flux. It must meet the challenges of advances in bioscience, newer diagnostic and therapeutic modalities, a changing health care environment, and interdisciplinary learning for problem solving; engender social responsibility; promote good provider-patient relations; stress primary care; and emphasize prevention.…

  17. Addressing canine and feline aggression in the veterinary clinic.

    PubMed

    Moffat, Kelly

    2008-09-01

    Handling aggressive dogs and cats in the veterinary clinic can be frustrating, time consuming, and injurious for both employee and animal. This article discusses the etiology of the aggressive dog and cat patient and how best to approach these cases. A variety of handling techniques, safety products, and drug therapy are reviewed.

  18. Addressing missing participant outcome data in dental clinical trials.

    PubMed

    Spineli, Loukia M; Fleming, Padhraig S; Pandis, Nikolaos

    2015-06-01

    Missing outcome data are common in clinical trials and despite a well-designed study protocol, some of the randomized participants may leave the trial early without providing any or all of the data, or may be excluded after randomization. Premature discontinuation causes loss of information, potentially resulting in attrition bias leading to problems during interpretation of trial findings. The causes of information loss in a trial, known as mechanisms of missingness, may influence the credibility of the trial results. Analysis of trials with missing outcome data should ideally be handled with intention to treat (ITT) rather than per protocol (PP) analysis. However, true ITT analysis requires appropriate assumptions and imputation of missing data. Using a worked example from a published dental study, we highlight the key issues associated with missing outcome data in clinical trials, describe the most recognized approaches to handling missing outcome data, and explain the principles of ITT and PP analysis.

  19. Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity

    PubMed Central

    Catenacci, Daniel V.T.

    2014-01-01

    The promise of ‘personalized cancer care’ with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demonstrated by molecular evolution through space (primary tumor to metastasis) and time (after therapy). These issues have become hurdles to advancing cancer treatment outcomes with novel molecularly targeted agents. Classic trial design paradigms are challenged by heterogeneity, as they are unable to test targeted therapeutics against low frequency genomic ‘oncogenic driver’ aberrations with adequate power. Usual accrual difficulties to clinical trials are exacerbated by low frequencies of any given molecular driver. To address these challenges, there is need for innovative clinical trial designs and strategies implementing novel diagnostic biomarker technologies to account for inter-patient molecular diversity and scarce tissue for analysis. Importantly, there is also need for pre-defined treatment priority algorithms given numerous aberrations commonly observed within any one individual sample. Access to multiple available therapeutic agents simultaneously is crucial. Finally intra-patient heterogeneity through time may be addressed by serial biomarker assessment at the time of tumor progression. This report discusses various ‘next-generation’ biomarker-driven trial designs and their potentials and limitations to tackle these recognized molecular heterogeneity challenges. Regulatory hurdles, with respect to drug and companion diagnostic development and approval, are considered. Focus is on the ‘Expansion Platform Design Types I and II’, the latter demonstrated with a first example, ‘PANGEA: Personalized Anti-Neoplastics for Gastro-Esophageal Adenocarcinoma’. Applying integral medium-throughput genomic and proteomic assays along with

  20. Structural Vulnerability: Operationalizing the Concept to Address Health Disparities in Clinical Care.

    PubMed

    Bourgois, Philippe; Holmes, Seth M; Sue, Kim; Quesada, James

    2017-03-01

    The authors propose reinvigorating and extending the traditional social history beyond its narrow range of risk behaviors to enable clinicians to address negative health outcomes imposed by social determinants of health. In this Perspective, they outline a novel, practical medical vulnerability assessment questionnaire that operationalizes for clinical practice the social science concept of "structural vulnerability." A structural vulnerability assessment tool designed to highlight the pathways through which specific local hierarchies and broader sets of power relationships exacerbate individual patients' health problems is presented to help clinicians identify patients likely to benefit from additional multidisciplinary health and social services. To illustrate how the tool could be implemented in time- and resource-limited settings (e.g., emergency department), the authors contrast two cases of structurally vulnerable patients with differing outcomes. Operationalizing structural vulnerability in clinical practice and introducing it in medical education can help health care practitioners think more clearly, critically, and practically about the ways social structures make people sick. Use of the assessment tool could promote "structural competency," a potential new medical education priority, to improve understanding of how social conditions and practical logistics undermine the capacities of patients to access health care, adhere to treatment, and modify lifestyles successfully. Adoption of a structural vulnerability framework in health care could also justify the mobilization of resources inside and outside clinical settings to improve a patient's immediate access to care and long-term health outcomes. Ultimately, the concept may orient health care providers toward policy leadership to reduce health disparities and foster health equity.

  1. Shifting the clinical teaching paradigm in undergraduate nursing education to address the nursing faculty shortage.

    PubMed

    Richardson, Hila; Gilmartin, Mattia J; Fulmer, Terry

    2012-04-01

    To address the faculty shortage problem, schools of nursing are reexamining how they provide clinical education to undergraduate students to find ways to use faculty resources more efficiently and to maintain student enrollment. We describe a unique clinical teaching model implemented at the New York University College of Nursing. The new model currently being evaluated shifts from the traditional clinical education model, in which all clinical education is in a hospital or agency setting, to a model that substitutes high-fidelity human patient simulation for up to half of the clinical education experience. This article describes the clinical teaching model and its effects on nurse faculty capacity.

  2. Event-Specific Prevention: Addressing College Student Drinking During Known Windows of Risk

    PubMed Central

    Neighbors, Clayton; Walters, Scott T.; Lee, Christine M.; Vader, Amanda M.; Vehige, Tamara; Szigethy, Thomas; DeJong, William

    2007-01-01

    The unique drinking patterns of college students call for Event-Specific Prevention (ESP) strategies that address college student drinking associated with peak times and events. Despite limited research evaluating ESP, many college campuses are currently implementing programming for specific events. The present paper provides a review of existing literature related to ESP and offers practical guidance for research and practice. The prevention typology proposed by DeJong and Langford (2002) provides a framework for strategic planning, suggesting that programs and policies should address problems at the individual, group, institution, community, state, and society level, and that these interventions should focus on knowledge change, environmental change, health protection, and intervention and treatment services. From this typology, specific examples are provided for comprehensive program planning related to orientation/beginning of school year, homecoming, 21st birthday celebrations, spring break, and graduation. In addition, the University of Connecticut’s efforts to address problems resulting from its annual Spring Weekend are described as an illustration of how advance planning by campus and community partners can produce a successful ESP effort. PMID:17616260

  3. Vocal imitation in parrots allows addressing of specific individuals in a dynamic communication network.

    PubMed

    Balsby, Thorsten J S; Momberg, Jane Vestergaard; Dabelsteen, Torben

    2012-01-01

    Parrots in captivity are known for their ability to vocally imitate humans and recently it has been shown that wild-living orange-fronted conures are able to immediately imitate other individuals' contact calls. The function of this exceptional ability to imitate remains unclear. However, orange-fronted conures live in fission-fusion flocks where they encounter many different individuals every day, and it is possible that their vocal imitation ability is a flexible means to address a specific individual within a flock. We tested this via playback to short-term captive wild conures. Test birds were placed together in pairs in outdoor aviaries to form simple flocks. To simulate imitation of a specific individual these pairs received playback of contact calls that primarily imitate one of the two birds. Overall, individuals that received simulated vocal imitations of its calls responded more frequently and faster than the other individual. This suggests that orange-fronted conures can use imitations of contact calls to address specific individuals of a flock. In the discussion we argue that the fission-fusion flock dynamics of many parrot species has been an important factor in evolving conures' and other parrots' exceptional ability to imitate.

  4. Using Systems Approaches to Address Challenges for Clinical Implementation of Pharmacogenomics

    PubMed Central

    Karnes, Jason H; Van Driest, Sara; Bowton, Erica A; Weeke, Peter E; Mosley, Jonathan D; Peterson, Josh F; Denny, Joshua C

    2014-01-01

    Many genetic variants have been shown to affect drug response through changes in drug efficacy and likelihood of adverse effects. Much of pharmacogenomic science has focused on discovering and clinically implementing single gene variants with large effect sizes. Given the increasing complexities of drug responses and their variability, a systems approach may be enabling for discovery of new biology in this area. Further, systems approaches may be useful in addressing challenges in moving these data to clinical implementation, including creation of predictive models of drug response phenotypes, improved clinical decision-making through complex biological models, improving strategies for integrating genomics into clinical practice, and evaluating the impact of implementation programs on public health. PMID:24319008

  5. Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials

    PubMed Central

    Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M.; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G.; Liu, Tasnuva M.; Margevicius, Seunghee; Miller, Dawn M.; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D.

    2016-01-01

    Purpose Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. Patients and Methods A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient’s barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Results Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. Conclusion These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was

  6. A systematic review of strategies to address the clinical nursing faculty shortage.

    PubMed

    Wyte-Lake, Tamar; Tran, Kim; Bowman, Candice C; Needleman, Jack; Dobalian, Aram

    2013-05-01

    This systematic review provides a comprehensive assessment of models used to expand the ranks of clinical nursing faculty. Nursing faculty shortages constrict the pipeline for educating nurses and make addressing the projected nursing shortage more difficult. Schools of nursing have denied admission to qualified applicants, citing insufficient numbers of nursing faculty as one major reason. Using key search terms in PubMed(®) and CINAHL(®), we identified 14 peer-reviewed articles published between 1980 and 2010 about models for expanding clinical faculty. Partnership models (n = 11) and expanded use of faculty resources (n = 9) were the most common strategies. Few (n = 8) studies assessed program efficacy. A need was identified for studies to assess the effect of alternative models on educational capacity and student performance and to examine the subcomponents of academic-practice partnerships and other innovative approaches to understand the essential factors necessary to implement successful programs.

  7. Presidential address. American College of Clinical Pharmacology has provided a variety of educational opportunities.

    PubMed

    Lathers, C M

    1995-04-01

    At the current time, the College is in an excellent position to support the educational needs of its growing membership. The fund balance has increased over the past few years and is continuing to increase during the current year. The unprecedented speed of changes in the health care environment in which all clinical pharmacologists are now working necessitates that the American College of Clinical Pharmacology continually examine and update its Strategic Plan and Long Range Goals to allow all of its members to keep abreast of these changes. As hospitals, medical schools, and other allied health colleges address the need for economic accountability, as educators in medical and pharmacy and other schools encounter state and federal reductions in financial assistance to students, and as new roles are developed for the clinical pharmacologists working within the professions of medicine, pharmacy and allied health specialties, the College must maintain its role as a leader for all clinical pharmacologists. The success of the College will be directly related to the effort invested by all of the committee members and chairpersons, the Board of Regents, the Officers of the College, and most of all, the membership. During the next two years, I look forward to working with the entire membership to encourage growth of the College.

  8. To What Extent Is Criminal Justice Content Specifically Addressed in MSW Programs?

    ERIC Educational Resources Information Center

    Epperson, Matthew W.; Roberts, Leslie E.; Ivanoff, Andre; Tripodi, Stephen J.; Gilmer, Christy N.

    2013-01-01

    This study examined the extent to which criminal justice content is addressed in all CSWE-accredited MSW programs in the United States ("N"?=?192). Criminal justice content was measured in three areas: (1) dual or joint degree programs, (2) concentrations or specializations, and (3) coursework. Excluding social work and law classes, 22%…

  9. Issue-Specific Barriers to Addressing Environmental Issues in the Classroom: An Exploratory Study

    ERIC Educational Resources Information Center

    Kim, Chankook; Fortner, Rosanne W.

    2006-01-01

    To explore issue-specific barriers to teaching environmental issues, the authors investigated secondary science teachers' perceived current and preferred teaching levels for 23 environmental issues and perceived barriers to teaching the selected issues. Subjects in this graduate project were 41 secondary science teachers self-selected to answer a…

  10. Management of type 2 diabetes: more evidence is required to address the clinical and contextual facets.

    PubMed

    Hernandez-Jimenez, Sergio; Aguilar-Salinas, Carlos A; Mehta, Roopa; Rull, Juan A; Gómez-Pérez, Francisco J

    2011-03-01

    Evidence based medicine has changed the manner in which medicine is practiced and learned. Epidemiological studies, meta-analyses and systematic reviews have been used to create algorithms for the treatment of hyperglycemia in patients with type 2 diabetes. Recently, several randomized controlled trials (i.e. ACCORD, ADVANCE, VADT) have generated new and valuable information regarding the benefits and risks of achieving optimal glucose control. As a result, guidelines and algorithms have been updated. However, many aspects remain controversial. In this article, the clinical implications of the existing guidelines are critically analyzed. The limitations of the current guidelines include the lack of applicability to relevant diabetic subgroups, the exclusion of important factors that modify the therapeutic response to glucose-lowering agents and the limited recognition of the importance of the socioeconomic situation on treatment efficacy. Many subgroups of patients have not been included in the studies used to generate recommendations. There is insufficient evidence to support the use of current treatment recommendations in patients with early onset type 2 diabetes, patients with advanced microvascular complications, and the elderly with or without chronic complications. The characteristics of the candidates for conservative or intensive treatment are poorly defined. Interventions are recommended without considering clinical variables (i.e. obesity, time since diagnosis or prolonged exposure to hyperglycemia) that may modify treatment efficacy and the occurrence of side effects. Finally, no consideration is given to the socioeconomic context of the population in which the guidelines are to be applied. In summary, this manuscript highlights the key areas which require further work. If these issues are adequately addressed, the guidelines for the management of type 2 diabetes will be relevant and applicable to all diabetic groups.

  11. Insular primary glioblastomas with IDH mutations: Clinical and biological specificities.

    PubMed

    Hata, Nobuhiro; Hatae, Ryusuke; Yoshimoto, Koji; Murata, Hideki; Kuga, Daisuke; Akagi, Yojiro; Sangatsuda, Yuhei; Suzuki, Satoshi O; Iwaki, Toru; Mizoguchi, Masahiro; Iihara, Koji

    2017-01-24

    Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower-grade gliomas. Thus, it is unclear whether IDH mutation is a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors (sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype (IDH-wt) pGBMs. IDH-mutant (IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte-sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mut pGBMs arising from insular cortex region, the molecular backgrounds of which are similar to sGBMs.

  12. Discovery and Subtyping of Neo-Epitope Specific T-Cell Responses for Cancer Immunotherapy: Addressing the Mutanome.

    PubMed

    Diken, Mustafa; Vormehr, Mathias; Grunwitz, Christian; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2017-01-01

    Cancer accumulates 10s to 1000s of genomic mutations of which a fraction is immunogenic and may serve as an Achilles' heel of tumor cells. Mutation-specific T cells can recognize these antigens and destroy malignant cells. Strategies to immunotherapeutically address individual tumor mutations employing peptide or mRNA based vaccines are now actively investigated in mice and humans. An important step of determining the therapeutic potential of a mutanome vaccine is the detection of mutation reactive T-cell responses. In this chapter we provide protocols to identify and subtype mutation specific T cells in mice based on IFN-γ ELISpot and flow cytometry.

  13. The SSC cycle: a PDCA approach to address site-specific characteristics in a continuous shallow water quality monitoring project.

    PubMed

    Miles, Eduardo J

    2008-05-01

    In any water quality-monitoring project there are several critical success factors that must be adequately addressed in order to ensure the implementation and realization of the monitoring objectives. Site selection is one of these critical success factors. The monitoring sites must be selected to comply with the monitoring and data quality objectives. In the real world, ideal monitoring setting conditions are difficult to achieve, and compromises must be made in order to locate the monitoring stations that best represent the environment to be monitored. Site-specific characteristics are all the environmental, logistical and management factors particular to the monitoring site, that could influence the fulfilment of the monitoring and data quality objectives. Therefore, during the site selection process, it is essential to properly consider and evaluate these site-specific characteristics. The SSC cycle was developed with this goal in mind, to assist the monitoring team to systematically address site-specific characteristics. The cycle is a methodology to organize the site-specific characteristics in different categories, and to ensure a comprehensive overview of these characteristics throughout the project life cycle.

  14. Hispanic Women's Expectations of Campus-Based Health Clinics Addressing Sexual Health Concerns

    ERIC Educational Resources Information Center

    Stephens, Dionne P.; Thomas, Tami L.

    2011-01-01

    Although the number of Hispanic women attending postsecondary institutions has significantly increased in the past decade, knowledge about their use of campus health services to address sexuality-related issues remains low. Increased information about this population is crucial given that sexual health indicators have shown Hispanic women in…

  15. Linking HIV-positive adolescents to care in 15 different clinics across the United States: creating solutions to address structural barriers for linkage to care.

    PubMed

    Philbin, Morgan M; Tanner, Amanda E; Duval, Anna; Ellen, Jonathan; Kapogiannis, Bill; Fortenberry, J Dennis

    2014-01-01

    Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents' readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering

  16. Implementing Peer Learning in Clinical Education: A Framework to Address Challenges In the "Real World".

    PubMed

    Tai, Joanna Hong Meng; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

    2017-01-01

    Phenomenon: Peer learning has many benefits and can assist students in gaining the educational skills required in future years when they become teachers themselves. Peer learning may be particularly useful in clinical learning environments, where students report feeling marginalized, overwhelmed, and unsupported. Educational interventions often fail in the workplace environment, as they are often conceived in the "ideal" rather than the complex, messy real world. This work sought to explore barriers and facilitators to implementing peer learning activities in a clinical curriculum.

  17. Addressing anxiety in vivo in physiotherapy treatment of women with severe vaginismus: a clinical approach.

    PubMed

    Rosenbaum, Talli

    2011-01-01

    Physiotherapy for the treatment of vaginismus is perceived as an intervention aimed to normalize muscle tone of the pelvic floor in order to allow vaginal penetration in accordance with the traditional view of vaginal spasm as its defining feature. Newer definitions recognize the experience of anxiety as well as pain, and effective treatment approaches should address these components as well. Physiotherapists often encounter women who, as a result of severe anxiety, are unable to undergo examination and treatment, despite their expressed desire to do so. This article describes a therapeutic intervention designed to help women with vaginismus prepare for examination and treatment by addressing the component of anxiety in real-life situations. This approach is also appropriate for nurse practitioners and physicians who work with this patient population and may be adapted for sex therapists to teach as a home exercise.

  18. Addressing Heavy Drinking in Smoking Cessation Treatment: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Kahler, Christopher W.; Metrik, Jane; LaChance, Heather R.; Ramsey, Susan E.; Abrams, David B.; Monti, Peter M.; Brown, Richard A.

    2008-01-01

    Heavy alcohol use frequently co-occurs with cigarette smoking and may impede smoking cessation. This clinical trial examined whether smoking cessation treatment that incorporates brief alcohol intervention can improve smoking cessation outcomes (7-day verified point prevalence abstinence) and reduce drinks consumed per week. Heavy drinkers seeking…

  19. Teaching to Transform? Addressing Race and Racism in the Teaching of Clinical Social Work Practice

    ERIC Educational Resources Information Center

    Varghese, Rani

    2016-01-01

    Faculty members are key stakeholders to support social work students' learning about race and racism in practice and to promote the professional standards established by the field. This qualitative study examines how 15 clinical social work faculty members teaching advanced practice in the Northeast conceptualize and incorporate their…

  20. Healthy me: A gender-specific program to address body image concerns and risk factors among preadolescents.

    PubMed

    McCabe, Marita P; Connaughton, Catherine; Tatangelo, Gemma; Mellor, David; Busija, Lucy

    2017-03-01

    This study evaluated a gender-specific, school-based program to promote positive body image and address risk factors for body dissatisfaction. In total, 652 children aged 8-10 years participated (335 intervention, 317 wait-list control). Children participated in four 60min sessions and a recap session at three months post-intervention. The broad content areas were body image, peer relationships, media awareness, healthy diet, and exercise. The activities and examples for each session were gender specific. The recap session was an overview of the four sessions. Assessment measures were completed at pre-intervention, post-intervention, and after the recap. Boys and girls in the intervention demonstrated higher muscle esteem and vegetable intake at post-intervention, compared to children in the control condition. Boys and girls demonstrated higher body esteem, muscle esteem and fruit and vegetable intake at the recap. Boys in the intervention demonstrated less investment in masculine gender norms at post-intervention and at recap.

  1. Mobile farm clinic outreach to address health conditions among Latino migrant farmworkers in Georgia.

    PubMed

    Luque, John S; Reyes-Ortiz, Carlos; Marella, Prasen; Bowers, Angelica; Panchal, Viral; Anderson, Lisa; Charles, Simone

    2012-01-01

    Agricultural labor involves exposure to many occupational hazards, some of which can lead to chronic health conditions. The purpose of this study was to conduct an occupational health needs assessment of illnesses and work-related injuries among a Latino migrant farmworker population (recruited to harvest Vidalia onions) in South Georgia. Study data included survey responses from 100 farmworkers attending mobile farm clinics in 2010 at their worker housing residences, supplemented by medical diagnoses data from the same clinics collected over 3 years (2009-2011) for 1161 farmworkers at six different farms. From the survey, the main health problems reported were hypertension (25%), eye problems (12%), musculoskeletal problems (11%), diabetes (10%), and depression (7%). In multivariate analyses, depression scores were associated with having a history of musculoskeletal problems (p = .002). According to the mobile farm clinic data, the most common medical diagnoses included back pain (11.8%), hypertension (11.4%), musculoskeletal problems (11.3%), gastrointestinal disorders (8.6%), eye problems (7.2%), dermatitis or rash (7.0%), and tinea or fungal skin infections (5.6%). The study identified eye and musculoskeletal problems as the major occupational health conditions for this population of farmworkers.

  2. Potential Strategies to Address the Major Clinical Hurdles Facing Stem Cell Regenerative Therapy for Cardiovascular Disease: A Review

    PubMed Central

    Nguyen, Patricia K.; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C.

    2017-01-01

    Importance While progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical translation still exist that have thwarted the delivery of cell therapy to the bedside. Objective The purpose of this review is to summarize the major current hurdles for the clinical implementation of stem cell therapy and discuss potential strategies to overcome them. Evidence Review Information for this review was obtained through a search of PubMed and the Cochrane database for English language studies published between January 1, 2000 and June 15, 2016. Ten randomized clinical trials and eight systematic reviews were included in this review. Findings One of the major clinical hurdles facing the routine implementation of stem cell therapy is the limited and inconsistent benefit observed thus far. Reasons for this are unclear but may be due to poor cell retention and survival, as suggested by numerous preclinical studies and a handful of human studies incorporating cell fate imaging. Additional cell fate imaging studies in humans are needed to determine how these factors contribute to limited efficacy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: 1) co-administering of immunosuppressive and pro-survival agents, 2) delivering cardioprotective factors packaged in exosomes rather than the cells themselves, and 3) using tissue engineering strategies to provide structural support for cells. If larger grafts are achieved using the aforementioned strategies, it will be imperative to carefully monitor the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Conclusions and Relevance Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical hurdles outlined herein before the next wave of large

  3. Pedagogical Tools to Address Clinical Anatomy and Athletic Training Student Learning Styles

    ERIC Educational Resources Information Center

    Mazerolle, Stephanie; Yeargin, Susan

    2010-01-01

    Context: A thorough knowledge of anatomy is needed in four of the six domains of athletic training: prevention, injury/condition recognition, immediate care, and treatment/rehabilitation. Students with a solid foundation can achieve competency in these specific domains. Objective: To provide educators with pedagogical tools to promote a deeper…

  4. Specific Gene Loci of Clinical Pseudomonas putida Isolates

    PubMed Central

    Molina, Lázaro; Udaondo, Zulema; Duque, Estrella; Fernández, Matilde; Bernal, Patricia; Roca, Amalia; de la Torre, Jesús; Ramos, Juan Luis

    2016-01-01

    Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host’s immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA) systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria. PMID:26820467

  5. HPV 9G DNA chip: 100% clinical sensitivity and specificity.

    PubMed

    An, Heejung; Song, Keum-Soo; Nimse, Satish Balasaheb; Kim, Junghoon; Nguyen, Van-Thuan; Ta, Van-Thao; Sayyed, Danishmalik Rafiq; Kim, Taisun

    2012-03-01

    We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products. The discrimination of HPV genotypes in the 151 HPV-positive clinical samples by the HPV 9G DNA chip test were 100% identical with the sequencing analysis. The clinical sensitivities of HPV genotyping by the HPV 9G DNA chip test and a commercial HPV DNA chip test were 100% and 88%, respectively. However, the clinical specificities of HPV genotyping by the HPV 9G DNA chip test and the commercial HPV DNA chip test were 100% and 94%, respectively. The 100% clinical sensitivity and specificity of the HPV 9G DNA chip test make it a promising diagnostic tool for HPV genotyping.

  6. Tailoring clinical services to address the unique needs of adolescents from the pregnancy test to parenthood.

    PubMed

    Moriarty Daley, Alison; Sadler, Lois S; Dawn Reynolds, Heather

    2013-04-01

    Clinicians across disciplines and practice settings are likely to encounter adolescents who are at risk for a pregnancy. In 2010, 34.2/1000 15-19-year-old teens had a live birth in the United States, many more will seek care for a pregnancy scare or options counseling. Teen mothers are also at risk for a second or higher-order pregnancy during adolescence. This paper provides clinicians with adolescent-friendly clinical and counseling strategies for pregnancy prevention, pre- and post-pregnancy test counseling, pregnancy-related care, and a review of the developmental challenges encountered by teens in the transition to parenthood. Clinicians are in a better position to approach the developmental, health and mental health needs of adolescents related to pregnancy if they understand and appreciate the obstacles adolescents may face negotiating the healthcare system. In addition, when clinical services are specially tailored to the needs of the adolescent, fewer opportunities will be lost to prevent unintended pregnancies, assist teens into timely prenatal services, and improve outcomes for their pregnancies and the transition to parenthood.

  7. Tailoring Clinical Services to Address the Unique Needs of Adolescents from the Pregnancy Test to Parenthood

    PubMed Central

    Daley, Alison Moriarty; Sadler, Lois S.; Reynolds, Heather Dawn

    2013-01-01

    Clinicians across disciplines and practice settings are likely to encounter adolescents who are at risk for a pregnancy. In 2010, 34.2/1000 15–19 year old teens had a live birth in the United States, many more will seek care for a pregnancy scare or options counseling. Teen mothers are also at risk for a second or higher order pregnancy during adolescence. This paper provides clinicians with adolescent-friendly clinical and counseling strategies for pregnancy prevention, pre- and post-pregnancy test counseling, pregnancy-related care, and a review of the developmental challenges encountered by teens in the transition to parenthood. Clinicians are in a better position to approach the developmental, health and mental health needs of adolescents related to pregnancy if they understand and appreciate the obstacles adolescents may face negotiating the health care system. In addition, when clinical services are specially tailored to the needs of the adolescent, fewer opportunities will be lost to prevent unintended pregnancies, assist teens into timely prenatal services, and improve outcomes for their pregnancies and the transition to parenthood. PMID:23522339

  8. A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge.

    PubMed

    Steck, R; Epari, D R; Schuetz, M A

    2010-07-01

    The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today.

  9. Practical guidelines addressing ethical issues pertaining to the curation of human locus-specific variation databases (LSDBs)

    PubMed Central

    Povey, Sue; Al Aqeel, Aida I; Cambon-Thomsen, Anne; Dalgleish, Raymond; den Dunnen, Johan T; Firth, Helen V; Greenblatt, Marc S; Barash, Carol Isaacson; Parker, Michael; Patrinos, George P; Savige, Judith; Sobrido, Maria-Jesus; Winship, Ingrid; Cotton, Richard GH

    2010-01-01

    More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO). Hum Mutat 31:–6, 2010. © 2010 Wiley-Liss, Inc. PMID:20683926

  10. Are current standards of reporting quality for clinical trials sufficient in addressing important sources of bias?

    PubMed

    Mills, Edward J; Ayers, Dieter; Chou, Roger; Thorlund, Kristian

    2015-11-01

    Determining the quality of a randomized clinical trial (RCT) is necessary for decision-makers to determine the believability and applicability of the trial findings. Issues that are likely to affect the utility of RCT evidence include issues of bias, random error and applicability. In this article we focus primarily on issues of bias and examine the evidence for whether reporting methodological items, including allocation concealment, sequence generation, and blinding of participants can be relied upon as evidence of bias. We present the findings of a systematic review of meta-epidemiological studies and a simulation study demonstrating that commonly examined sources of bias likely play little role in treatment exaggeration. We discuss other issues that may additionally influence trial outcomes including sample size, publication bias, and expertise of trialists. We conclude by discussing strategies to moderate the effect of known biases in assessing overall estimates of treatment effects.

  11. Developing a contextual consciousness: learning to address gender, societal power, and culture in clinical practice.

    PubMed

    Esmiol, Elisabeth E; Knudson-Martin, Carmen; Delgado, Sarah

    2012-10-01

    Despite the growing number of culturally sensitive training models and considerable literature on the importance of training clinicians in larger contextual issues, research examining how students learn to apply these issues is limited. In this participatory action research project, we systematically studied our own process as marriage and family therapy (MFT) practicum students developing a contextual consciousness. Using grounded theory, we identified a three-stage process: (a) raised awareness through clinical experimentation and developing a theoretical rationale, (b) reflective questioning involving challenging old perspectives and experiencing positive client-therapist interactions, and (c) an intentional new lens based on personal responsibility and commitment. Creating and maintaining a contextual lens required a safe, empowering group dynamic and accessing other forms of support and accountability after the practicum.

  12. The Infectious Diseases Clinical Research Program: addressing the challenge of infections related to war injuries and skin and soft tissues.

    PubMed

    Martin, Gregory J; Tribble, David R

    2010-07-01

    The Infectious Diseases Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded network of military treatment and research facilities coordinated through USU and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF). IDCRP functions in collaboration with the NIAID, universities, and industry to address infectious diseases threats to the U.S. military and to the nation. Although IDCRP has projects in diseases from HIV to tuberculosis, a major focus has been on skin, soft-tissue, and war-related infections.

  13. Patient and healthcare perspectives on the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic: a qualitative study

    PubMed Central

    Sinclair, Shane; McConnell, Shelagh; Raffin Bouchal, Shelley; Ager, Naree; Booker, Reanne; Enns, Bert; Fung, Tak

    2015-01-01

    Objectives The purpose of this study was to use a qualitative approach to better understand the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic from the perspectives of patients and healthcare providers. Setting Participants were recruited from the bone marrow transplant clinic of a large urban outpatient cancer care centre in western Canada. Participants: Focus groups were conducted with patients (n=7) and healthcare providers (n=9) to explore the importance of addressing spiritual issues across the treatment trajectory and to identify factors associated with effectively addressing these needs. Results Data were analysed using the qualitative approach of latent content analysis. Addressing spiritual issues was understood by patients and healthcare providers, as a core, yet under addressed, component of comprehensive care. Both sets of participants felt that addressing basic spiritual issues was the responsibility of all members of the interdisciplinary team, while recognising the need for specialised and embedded support from a spiritual care professional. While healthcare providers felt that the impact of the illness and treatment had a negative effect on patients’ spiritual well-being, patients felt the opposite. Skills, challenges, key time points and clinical indicators associated with addressing spiritual issues were identified. Conclusions Despite a number of conceptual and clinical challenges associated with addressing spiritual issues patients and their healthcare providers emphasised the importance of an integrated approach whereby basic spiritual issues are addressed by members of the interdisciplinary team and by an embedded spiritual care professional, who in addition also provides specialised support. The identification of clinical issues associated with addressing spiritual needs provides healthcare providers with clinical guidance on how to better integrate this aspect of care into

  14. The 2011 Leona Tyler Award Address: The Relationship--And Its Relationship to the Common and Specific Factors of Psychotherapy

    ERIC Educational Resources Information Center

    Wampold, Bruce E.; Budge, Stephanie L.

    2012-01-01

    A debate exists about whether the common factors or specific ingredients are critical to producing the benefits of psychotherapy. A model of the relationship, based on evolved human characteristics related to healing, is presented that integrates common factors and specific ingredients. After the initial bond is formed, the relationship involves…

  15. Hybrid specification, storage, retrieval and runtime application of clinical guidelines.

    PubMed

    Shahar, Y

    2006-06-01

    Clinical guidelines are a major tool in improving the quality of medical care. However, most guidelines are in free text, are not machine-comprehensible and are not easily accessible to clinicians at the point of care. We have designed and implemented a web-based, modular, distributed architecture, the Digital Electronic Guideline Library (DeGeL), which facilitates gradual conversion of clinical guidelines from text to a formal representation in the chosen target guideline ontology. The architecture supports guideline classification, semantic markup, context-sensitive search, browsing, run-time application and retrospective quality assessment. The DeGeL hybrid meta-ontology includes elements common to all guideline ontologies, such as semantic classification and domain knowledge; it also includes four content-representation formats: free text, semi-structured text, semi-formal representation and a formal representation. These formats support increasingly sophisticated computational tasks. Guidelines can thus be in a hybrid representation in which guidelines, and even parts of the same guideline, might exist at different formalisation levels. We have also developed and rigorously evaluated a methodology and an associated web-based tool, Uruz, for gradually structuring and semi-formalising free-text clinical guidelines. Finally, we have designed, implemented and evaluated a new approach, the hybrid runtime application model, for supporting runtime application of clinical guidelines that are not necessarily in a machine-comprehensible format; in particular, when the guideline is in a semi-formal representation and the patient's data are either in an electronic medical record or in a paper format. The tool implementing this new approach, the Spock module, is customised at this point to the Asbru guideline specification language and exploits the hybrid structure of guidelines in DeGeL. The Spock module also exploits our temporal-abstraction mediator to the patient

  16. Community health clinical education in Canada: part 2--developing competencies to address social justice, equity, and the social determinants of health.

    PubMed

    Cohen, Benita E; Gregory, David

    2009-01-01

    Recently, several Canadian professional nursing associations have highlighted the expectations that community health nurses (CHNs) should address the social determinants of health and promote social justice and equity. These developments have important implications for (pre-licensure) CHN clinical education. This article reports the findings of a qualitative descriptive study that explored how baccalaureate nursing programs in Canada address the development of competencies related to social justice, equity, and the social determinants of health in their community health clinical courses. Focus group interviews were held with community health clinical course leaders in selected Canadian baccalaureate nursing programs. The findings foster understanding of key enablers and challenges when providing students with clinical opportunities to develop the CHN role related to social injustice, inequity, and the social determinants of health. The findings may also have implications for nursing programs internationally that are addressing these concepts in their community health clinical courses.

  17. Institution-Specific Victimization Surveys: Addressing Legal and Practical Disincentives to Gender-Based Violence Reporting on College Campuses.

    PubMed

    Cantalupo, Nancy Chi

    2014-07-01

    This review brings together both the legal literature and original empirical research regarding the advisability of amending the Jeanne Clery Disclosure of Campus Security Policy and Campus Crime Statistics Act or creating new Department of Education regulations to mandate that all higher education institutions survey their students approximately every 5 years about students' experiences with sexual violence. Legal research conducted regarding the three relevant federal legal regimes show inconsistent incentives for schools to encourage victim reporting and proactively address sexual violence on campus. Moreover, the original research carried out for this article shows that the experience of institutions that have voluntarily conducted such surveys suggests many benefits not only for students, prospective students, parents, and the general public but also for schools themselves. These experiences confirm the practical viability of a mandated survey by the Department of Education.

  18. Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis

    PubMed Central

    Arboix, Adrià; Alió, Josefina

    2010-01-01

    This article provides the reader with an overview and up-date of clinical features, specific cardiac disorders and prognosis of cardioembolic stroke. Cardioembolic stroke accounts for 14-30% of ischemic strokes and, in general, is a severe condition; patients with cardioembolic infarction are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of cardioembolic infarction, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke’s aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The more common high risk cardioembolic conditions are atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy, and mitral rheumatic stenosis. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Holter monitoring. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. In our experience, in-hospital mortality in patients with early embolic recurrence (within the first 7 days) was 77%. Patients with alcohol abuse, hypertension, valvular heart disease, nausea and vomiting, and previous cerebral infarction are at increased risk of early recurrent systemic embolization. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. PMID:21804774

  19. No clinical benefit of gender-specific total knee arthroplasty

    PubMed Central

    Zhu, Chen; Wang, Jiaxing; Cheng, Mengqi; Peng, Xiaochun; Wang, Qi; Zhang, Xianlong

    2014-01-01

    Background and purpose There is no consensus regarding the clinical relevance of gender-specific prostheses in total knee arthroplasty (TKA). We summarize the current best evidence in a comparison of clinical and radiographic outcomes between gender-specific prostheses and standard unisex prostheses in female patients. Methods We used the PubMed, Embase, Cochrane, Science Citation Index, and Scopus databases. We included randomized controlled trials published up to January 2013 that compared gender-specific prostheses with standard unisex prostheses in female patients who underwent primary TKAs. Results 6 trials involving 423 patients with 846 knee joints met the inclusion criteria. No statistically significant differences were observed between the 2 designs regarding pain, range of motion (ROM), knee scores, satisfaction, preference, complications, and radiographic results. The gender-specific design (Gender Solutions; Zimmer Inc, Warsaw, Indiana) reduced the prevalence of overhang. However, it had less overall coverage of the femoral condyles compared to the unisex group. In fact, the femoral prosthesis in the standard unisex group matched better than that in the gender-specific group. Interpretation Gender-specific prostheses do not appear to confer any benefit in terms of clinician- and patient-reported outcomes for the female knee. PMID:24954488

  20. Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity

    PubMed Central

    Garcia, John; Tahiliani, Jackie; Johnson, Nicole Marie; Aguilar, Sienna; Beltran, Daniel; Daly, Amy; Decker, Emily; Haverfield, Eden; Herrera, Blanca; Murillo, Laura; Nykamp, Keith; Topper, Scott

    2016-01-01

    Advances in DNA sequencing have made large, diagnostic gene panels affordable and efficient. Broad adoption of such panels has begun to deliver on the promises of personalized medicine, but has also brought new challenges such as the presence of unexpected results, or results of uncertain clinical significance. Genetic analysis of inherited cardiac conditions is particularly challenging due to the extensive genetic heterogeneity underlying cardiac phenotypes, and the overlapping, variable, and incompletely penetrant nature of their clinical presentations. The design of effective diagnostic tests and the effective use of the results depend on a clear understanding of the relationship between each gene and each considered condition. To address these issues, we developed simple, systematic approaches to three fundamental challenges: (1) evaluating the strength of the evidence suggesting that a particular condition is caused by pathogenic variants in a particular gene, (2) evaluating whether unusual genotype/phenotype observations represent a plausible expansion of clinical phenotype associated with a gene, and (3) establishing a molecular diagnostic strategy to capture overlapping clinical presentations. These approaches focus on the systematic evaluation of the pathogenicity of variants identified in clinically affected individuals, and the natural history of disease in those individuals. Here, we applied these approaches to the evaluation of more than 100 genes reported to be associated with inherited cardiomyopathies and arrhythmias including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia or cardiomyopathy, long QT syndrome, short QT syndrome, Brugada, and catecholaminergic polymorphic ventricular tachycardia, and to a set of related syndromes such as Noonan Syndrome and Fabry disease. These approaches provide a framework for delivering meaningful and accurate genetic test results to individuals with hereditary

  1. Non specific aorto-arteritis. Clinical picture, diagnosis and therapy.

    PubMed

    Miani, S; De Monti, M; Keller, G; Bordoni, M G; Bianchi, E; Giordanengo, F

    1999-06-01

    This study is aimed at analyzing clinical features, angiographic findings and evolution of Takayasu's arteritis and the criteria adopted to establish the indication for non-surgical versus operative treatment. Eighteen patients affected by non specific aortarteritis were observed and treated at our Department between 1973 and 1996. All patients met the American College of Rheumatology 1990 criteria of classification of Takayasu's arteritis. Sixteen patients were young females. Two patients were males. Nine patients underwent surgical procedures. One young female underwent a PTA. All eight asymptomatic patients were only medically treated. One patient died some days after an aorto-bicarotid bypass graft due to acute myocardial infarction. Two other patients died two and four years after intervention for renal and cardiac failure respectively. One patient after an aorto bicarotid bypass underwent a left hemiplegia due to thrombosis of the right graft branch. All the other 14 patients either surgically or medically treated are well and are under strict surveillance through rigorous follow-up. The 10 patients who underwent surgical or interventional radiological treatment were certainly the most seriously affected patients and were symptomatic (presented neurological disturbances or a severe hypertensive state). This fact explains, to some extent, the mortality and morbidity rate observed in this group. The seven medically treated patients were completely asymptomatic in spite of a major involvement of various vascular districts.

  2. Addressing Adherence Using Genotype-Specific PBPK Modeling—Impact of Drug Holidays on Tamoxifen and Endoxifen Plasma Levels

    PubMed Central

    Dickschen, Kristin J. R.; Willmann, Stefan; Hempel, Georg; Block, Michael

    2017-01-01

    Introduction: Tamoxifen is one of the most common treatment opportunities for hormonal positive breast cancer. Despite its good tolerability, patients demonstrate decreasing adherence over years impacting on therapeutic success. PBPK modeling was applied to demonstrate the impact of drug holidays on plasma levels of tamoxifen and its active metabolite endoxifen for different CYP2D6 genotypes. Materials and Methods: A virtual study with 24,000 patients was conducted in order to investigate the development of tamoxifen steady-state kinetics in patient groups of different CYP2D6 genotypes. The impact of drug holidays on steady-state kinetics was investigated assuming changing drug holiday scenarios. Results: Drug holidays in CYP2D6 extensive and intermediate metabolizers (EMs, IMs) exceeding 1 month lead to a decrease of endoxifen steady-state trough levels below the 5th percentile of the control group. Assuming drug holidays of 1, 2, or 3 months and administering a fixed-dose combination of 20 mg tamoxifen and 3 mg endoxifen EMs demonstrated re-established endoxifen steady-state trough levels after 5, 8, and 9 days. IMs receiving the same fixed-dose combination demonstrated re-established endoxifen steady-state trough levels after 7, 10, and 11 days. Discussion: The PBPK model impressively demonstrates the impact of drug holidays in different CYP2D6 genotypes on PK. Population simulation results indicate that drug holidays of more than 2 weeks cause a tremendous decrease of plasma levels despite the long half-life of tamoxifen. To improve therapeutic success, PBPK modeling allows identifying genotype-specific differences in PK following drug holidays and adequate treatment with loading doses. PMID:28382001

  3. Clinical and no-clinical setting specificities in first session short-term psychotherapy psychodrama group.

    PubMed

    Drakulić, Aleksandra Mindoljević

    2011-03-01

    Modern history of short-term group psychotherapy dates back to the late 1950-ies. From then to present day, this psychotherapeutic method has been used in various forms, from dynamic-oriented to cognitive behavioural psychotherapies. Although it has always been considered rather controversial, due its cost-effectiveness, it has been capturing more and more popularity. This paper presents the specificities of first session short-term psychotherapy psychodrama group through session work with two examined groups: a group of 20 adult women who suffer from mild or moderate forms of unipolar depression and a group of 20 students of the School of Medicine in Zagreb without any psychiatric symptomatology. The results indicate the high importance of having structure in first psychodrama session, of relating it with the previously thoroughly conducted, initial, clinical, interviews, and of the clarity and focus in terms of determining the goals of therapy, especially in a clinical context. This study also confirmed assumptions regarding the need for different approaches of warming-up in psychodrama, both in the clinical and in non-clinical samples. A psychodrama psychotherapist should have good time managing skills and capability to convert the time available into an opportunity for directly boosting the group energy and work on therapeutic alliance.

  4. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool

    PubMed Central

    Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S.; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M.; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T.; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

    2017-01-01

    Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are ‘fit for purpose’. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials. PMID:28222119

  5. Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool.

    PubMed

    Ramsey, Danielle; Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

    2017-01-01

    Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.

  6. Clinical Competence: General Ability or Case-Specific?

    ERIC Educational Resources Information Center

    Wimmers, Paul F.; Splinter, Ted A. W.; Hancock, Gregory R.; Schmidt, Henk G.

    2007-01-01

    Background: Before the 1970s, research into the development of clinical competence was mainly focused on general problem-solving abilities. The scope of research changed when Elstein and colleagues discovered that individual ability to solve clinical problems varies considerably across cases. It was concluded that problem solving abilities are…

  7. A Manual-Based Intervention to Address Clinical Crises and Retain Patients in the Treatment of Adolescents with Depression Study (TADS)

    ERIC Educational Resources Information Center

    May, Diane E.; Kratochvil, Christopher J.; Puumala, Susan E.; Silva, Susan G.; Rezac, Amy J.; Hallin, Mary J.; Reinecke, Mark A.; Vitiello, Benedetto; Weller, Elizabeth B.; Pathak, Sanjeev; Simons, Anne D.; March, John S.

    2007-01-01

    Objective: To describe a manual-based intervention to address clinical crises and retain participants in the Treatment for Adolescents with Depression Study (TADS). Method: The use of adjunct services for attrition prevention (ASAP) is described for adolescents (ages 12-17 years) during the 12-week acute treatment in TADS, from 2000 to 2003.…

  8. A Domain Analysis Model for eIRB Systems: Addressing the Weak Link in Clinical Research Informatics

    PubMed Central

    He, Shan; Narus, Scott P.; Facelli, Julio C.; Lau, Lee Min; Botkin, Jefferey R.; Hurdle, John F.

    2014-01-01

    Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. PMID:24929181

  9. A domain analysis model for eIRB systems: addressing the weak link in clinical research informatics.

    PubMed

    He, Shan; Narus, Scott P; Facelli, Julio C; Lau, Lee Min; Botkin, Jefferey R; Hurdle, John F

    2014-12-01

    Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support.

  10. A methodology for evaluation of a markup-based specification of clinical guidelines.

    PubMed

    Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan

    2008-11-06

    We introduce a three-phase, nine-step methodology for specification of clinical guidelines (GLs) by expert physicians, clinical editors, and knowledge engineers, and for quantitative evaluation of the specification's quality. We applied this methodology to a particular framework for incremental GL structuring (mark-up) and to GLs in three clinical domains with encouraging results.

  11. An Official American Thoracic Society Workshop Report. A Framework for Addressing Multimorbidity in Clinical Practice Guidelines for Pulmonary Disease, Critical Illness, and Sleep Disorders.

    PubMed

    Wilson, Kevin C; Gould, Michael K; Krishnan, Jerry A; Boyd, Cynthia M; Brozek, Jan L; Cooke, Colin R; Douglas, Ivor S; Goodman, Richard A; Joo, Min J; Lareau, Suzanne; Mularski, Richard A; Patel, Minal R; Rosenfeld, Richard M; Shanawani, Hasan; Slatore, Christopher; Sockrider, Marianna; Sufian, Beth; Thomson, Carey C; Wiener, Renda Soylemez

    2016-03-01

    Coexistence of multiple chronic conditions (i.e., multimorbidity) is the most common chronic health problem in adults. However, clinical practice guidelines have primarily focused on patients with a single disease, resulting in uncertainty about the care of patients with multimorbidity. The American Thoracic Society convened a workshop with the goal of establishing a strategy to address multimorbidity within clinical practice guidelines. In this Workshop Report, we describe a framework that addresses multimorbidity in each of the key steps of guideline development: topic selection, panel composition, identifying clinical questions, searching for and synthesizing evidence, rating the quality of that evidence, summarizing benefits and harms, formulating recommendations, and rating the strength of the recommendations. For the consideration of multimorbidity in guidelines to be successful and sustainable, the process must be both feasible and pragmatic. It is likely that this will be achieved best by the step-wise addition and refinement of the various components of the framework.

  12. Suicide Risk Protocols: Addressing the Needs of High Risk Youths Identified through Suicide Prevention Efforts and in Clinical Settings

    ERIC Educational Resources Information Center

    Heilbron, Nicole; Goldston, David; Walrath, Christine; Rodi, Michael; McKeon, Richard

    2013-01-01

    Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request…

  13. PET scans relate clinical picture to more specific nerve function

    SciTech Connect

    Ziporyn, T.

    1985-02-15

    This article describes the historical development of the use of positron emission tomography in studies of brain chemistry and the specific pathways associated with specific disease states. Fluorine-18 is used to label dopa since dopa can cross the blood-brain barrier. This radiopharmaceutical has been used to study the role of dopamine in Parkinson's disease and other motor disorders. The new PET technologies may also allow insight into the cause of variable responses to levo-dopa therapy.

  14. Specific Genetic Disorders and Autism: Clinical Contribution towards Their Identification

    ERIC Educational Resources Information Center

    Cohen, David; Pichard, Nadege; Tordjman, Sylvie; Baumann, Clarisse; Burglen, Lydie; Excoffier, Elsa; Lazar, Gabriela; Mazet, Philippe; Pinquier, Clement; Verloes, Alian; Heron, Delphine

    2005-01-01

    Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13…

  15. Addressing challenges in nursing education through a clinical instruction model based on a hybrid, inquiry-based learning framework.

    PubMed

    Holaday, Stephanie D; Buckley, Kathleen M

    2008-01-01

    This article describes an innovative hybrid, inquiry-based learning clinical instruction model used in accelerated baccalaureate nursing programs at three university nursing schools in the Washington DC metropolitan area. The authors describe student and faculty roles and offer examples of grading criteria. Nurse faculty and students from the three schools of nursing regard the clinical instruction model as a valuable teaching-learning approach that strengthens the relationship between theory and practice, prepares students to think critically and act effectively, and grooms students and faculty for a lifetime of learning in a changing world.

  16. Addressing narcissistic personality features in the context of medical care: integrating diverse perspectives to inform clinical practice.

    PubMed

    Magidson, J F; Collado-Rodriguez, A; Madan, A; Perez-Camoirano, N A; Galloway, S K; Borckardt, J J; Campbell, W K; Miller, J D

    2012-04-01

    Narcissistic personality disorder (NPD) is characterized by an unrealistic need for admiration, lack of empathy toward others, and feelings of superiority. NPD presents a unique and significant challenge in clinical practice, particularly in medical settings with limited provider contact time, as health professionals treat individuals who often require excessive admiration and have competing treatment needs. This practice review highlights real case examples across three distinct medically oriented clinical settings (inpatient and outpatient behavioral medicine and a Level I trauma center) to demonstrate the difficult and compromising situations that providers face when treating patients with general medical conditions and comorbid narcissistic personality features. The main goal of this article is to discuss the various challenges and obstacles associated with these cases in medical settings and discuss some strategies that may prove successful. A second goal is to bridge diverse conceptualizations of narcissism/NPD through the discussion of theoretical and empirical perspectives that can inform understanding of the clinical examples. Despite differing perspectives regarding the underlying motivation of narcissistic behavior, this practice review highlights that these paradigms can be integrated when sharing the same ultimate goal: to improve delivery of care across medically oriented clinical settings for patients with narcissistic features.

  17. Addressing healthcare.

    PubMed

    Daly, Rich

    2013-02-11

    Though President Barack Obama has rarely made healthcare references in his State of the Union addresses, health policy experts are hoping he changes that strategy this year. "The question is: Will he say anything? You would hope that he would, given that that was the major issue he started his presidency with," says Dr. James Weinstein, left, of the Dartmouth-Hitchcock health system.

  18. Serotype-specific differences in clinical manifestations of dengue.

    PubMed

    Balmaseda, Angel; Hammond, Samantha N; Pérez, Leonel; Tellez, Yolanda; Saborío, Saira Indira; Mercado, Juan Carlos; Cuadra, Ricardo; Rocha, Julio; Pérez, Maria Angeles; Silva, Sheyla; Rocha, Crisanta; Harris, Eva

    2006-03-01

    Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes of dengue virus (DENV 1-4). Although all four DENV serotypes cause a range of illness, defining precisely which clinical characteristics are associated with the distinct serotypes has been elusive. A cross-sectional study was conducted on 984 and 313 hospitalized children with confirmed DENV infections during two time periods, respectively, in the same hospitals in Nicaragua: a 3-year period (1999-2001) when DENV-2 accounted for 96% of the viruses identified, and the 2003 dengue season when DENV-1 predominated (87% of identified serotypes). When the two periods were compared, more shock (OR 1.91, 95% CI 1.35-2.71) and internal hemorrhage (OR 2.05, CI 1.16-3.78) were observed in the period when DENV-2 predominated, whereas increased vascular permeability was associated to a greater degree with the DENV-1 period (OR 2.36, CI 1.80-3.09). Compared with the DENV-2 period, the DENV-1 season was associated with more hospitalized primary dengue cases (OR 3.86, CI 2.72-5.48) and more primary DENV infections with severe manifestations (OR 2.93, CI 2.00-4.28). These findings provide new data to characterize the pathogenic potential of distinct DENV serotypes in human populations.

  19. Nonnutritive, low caloric substitutes for food sugars: clinical implications for addressing the incidence of dental caries and overweight/obesity.

    PubMed

    Roberts, Michael W; Wright, J Timothy

    2012-01-01

    Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate.

  20. Nonnutritive, Low Caloric Substitutes for Food Sugars: Clinical Implications for Addressing the Incidence of Dental Caries and Overweight/Obesity

    PubMed Central

    Roberts, Michael W.; Wright, J. Timothy

    2012-01-01

    Caries and obesity are two common conditions affecting children in the United States and other developed countries. Caries in the teeth of susceptible children have often been associated with frequent ingestion of fermentable sugars such as sucrose, fructose, glucose, and maltose. Increased calorie intake associated with sugars and carbohydrates, especially when associated with physical inactivity, has been implicated in childhood obesity. Fortunately, nonnutritive artificial alternatives and non-/low-caloric natural sugars have been developed as alternatives to fermentable sugars and have shown promise in partially addressing these health issues. Diet counseling is an important adjunct to oral health instruction. Although there are only five artificial sweeteners that have been approved as food additives by the Food and Drug Administration (FDA), there are additional five non-/low caloric sweeteners that have FDA GRAS (Generally Recognized as Safe) designation. Given the health impact of sugars and other carbohydrates, dental professionals should be aware of the nonnutritive non-/low caloric sweeteners available on the market and both their benefits and potential risks. Dental health professionals should also be proactive in helping identify patients at risk for obesity and provide counseling and referral when appropriate. PMID:22505906

  1. Addressing Missing Data Mechanism Uncertainty using Multiple-Model Multiple Imputation: Application to a Longitudinal Clinical Trial.

    PubMed

    Siddique, Juned; Harel, Ofer; Crespi, Catherine M

    2012-12-01

    We present a framework for generating multiple imputations for continuous data when the missing data mechanism is unknown. Imputations are generated from more than one imputation model in order to incorporate uncertainty regarding the missing data mechanism. Parameter estimates based on the different imputation models are combined using rules for nested multiple imputation. Through the use of simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal clinical trial of low-income women with depression where nonignorably missing data were a concern. We show that different assumptions regarding the missing data mechanism can have a substantial impact on inferences. Our method provides a simple approach for formalizing subjective notions regarding nonresponse so that they can be easily stated, communicated, and compared.

  2. Ethics Standards (HRPP) and Public Partnership (PARTAKE) to Address Clinical Research Concerns in India: Moving Toward Ethical, Responsible, Culturally Sensitive, and Community-Engaging Clinical Research

    PubMed Central

    Burt, Tal; Gupta, Yogendra K; Mehta, Nalin; Swamy, Nagendra; Sovani, Vishwas; Speers, Marjorie A

    2014-01-01

    Like other emerging economies, India’s quest for independent, evidence-based, and affordable healthcare has led to robust and promising growth in the clinical research sector, with a compound annual growth rate (CAGR) of 20.4% between 2005 and 2010. However, while the fundamental drivers and strengths are still strong, the past few years witnessed a declining trend (CAGR −16.7%) amid regulatory concerns, activist protests, and sponsor departure. And although India accounts for 17.5% of the world’s population, it currently conducts only 1% of clinical trials. Indian and international experts and public stakeholders gathered for a 2-day conference in June 2013 in New Delhi to discuss the challenges facing clinical research in India and to explore solutions. The main themes discussed were ethical standards, regulatory oversight, and partnerships with public stakeholders. The meeting was a collaboration of AAHRPP (Association for the Accreditation of Human Research Protection Programs)—aimed at establishing responsible and ethical clinical research standards—and PARTAKE (Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment)—aimed at informing and engaging the public in clinical research. The present article covers recent clinical research developments in India as well as associated expectations, challenges, and suggestions for future directions. AAHRPP and PARTAKE provide etiologically based solutions to protect, inform, and engage the public and medical research sponsors. PMID:25558428

  3. Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials.

    PubMed

    Jena, Bipulendu; Maiti, Sourindra; Huls, Helen; Singh, Harjeet; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2013-01-01

    Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR(+) T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19(+) tumor targets. This clone can be used to detect CD19-specific CAR(+) T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR(+) T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.

  4. Salud Para Su Corazon (health for your heart) community health worker model: community and clinical approaches for addressing cardiovascular disease risk reduction in Hispanics/Latinos.

    PubMed

    Balcazar, H; Alvarado, M; Ortiz, G

    2011-01-01

    This article describes 6 Salud Para Su Corazon (SPSC) family of programs that have addressed cardiovascular disease risk reduction in Hispanic communities facilitated by community health workers (CHWs) or Promotores de Salud (PS). A synopsis of the programs illustrates the designs and methodological approaches that combine community-based participatory research for 2 types of settings: community and clinical. Examples are provided as to how CHWs can serve as agents of change in these settings. A description is presented of a sustainability framework for the SPSC family of programs. Finally, implications are summarized for utilizing the SPSC CHW/PS model to inform ambulatory care management and policy.

  5. Clinical task-specific query expansion for the retrieval of scientifically rigorous research documents.

    PubMed

    Yoo, Sooyoung; Choi, Jinwook; Choi, Sungbin

    2010-01-01

    To support the practice of evidence-based medicine (EBM), clinically relevant and scientifically sound articles should be easily accessible. Due to the huge volume of medical literature and the low performance of present retrieval models, clinicians could only get relevant documents in the order of publication time. This study propose a new clinical task-specific retrieval technique that improves retrieval accuracy by exploiting clinical task-specific EBM terms to query expansion using co-occurrence analysis technique. The idea is aimed at selecting query expansion terms that are relevant to a specific clinical-task using task-specific EBM terms. Focusing on treatment and diagnosis tasks, the new method which was performed on the OHSUMED collection showed a further improved result than the existing method.

  6. Addressing Mental Health Disparities through Clinical Competence Not Just Cultural Competence: The Need for Assessment of Sociocultural Issues in the Delivery of Evidence-Based Psychosocial Rehabilitation Services

    PubMed Central

    Yamada, Ann-Marie; Brekke, John S

    2008-01-01

    Recognition of ethnic/racial disparities in mental health services has not directly resulted in the development of culturally responsive psychosocial interventions. There remains a fundamental need for assessment of sociocultural issues that have been linked with the expectations, needs, and goals of culturally diverse consumers with severe and persistent mental illness. The authors posit that embedding the assessment of sociocultural issues into psychosocial rehabilitation practice is one step in designing culturally relevant empirically supported practices. It becomes a foundation on which practitioners can examine the relevance of their interventions to the diversity encountered in everyday practice. This paper provides an overview of the need for culturally and clinically relevant assessment practices and asserts that by improving the assessment of sociocultural issues the clinical competence of service providers is enhanced. The authors offer a conceptual framework for linking clinical assessment of sociocultural issues to consumer outcomes and introduce an assessment tool adapted to facilitate the process in psychosocial rehabilitation settings. Emphasizing competent clinical assessment skills will ultimately offer a strategy to address disparities in treatment outcomes for understudied populations of culturally diverse consumers with severe and persistent mental illness. PMID:18778881

  7. Inaugural address

    NASA Astrophysics Data System (ADS)

    Joshi, P. S.

    2014-03-01

    From jets to cosmos to cosmic censorship P S Joshi Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400005, India E-mail: psj@tifr.res.in 1. Introduction At the outset, I should like to acknowledge that part of the title above, which tries to capture the main flavour of this meeting, and has been borrowed from one of the plenary talks at the conference. When we set out to make the programme for the conference, we thought of beginning with observations on the Universe, but then we certainly wanted to go further and address deeper questions, which were at the very foundations of our inquiry, and understanding on the nature and structure of the Universe. I believe, we succeeded to a good extent, and it is all here for you in the form of these Conference Proceedings, which have been aptly titled as 'Vishwa Mimansa', which could be possibly translated as 'Analysis of the Universe'! It is my great pleasure and privilege to welcome you all to the ICGC-2011 meeting at Goa. The International Conference on Gravitation and Cosmology (ICGC) series of meetings are being organized by the Indian Association for General Relativity and Gravitation (IAGRG), and the first such meeting was planned and conducted in Goa in 1987, with subsequent meetings taking place at a duration of about four years at various locations in India. So, it was thought appropriate to return to Goa to celebrate the 25 years of the ICGC meetings. The recollections from that first meeting have been recorded elsewhere here in these Proceedings. The research and teaching on gravitation and cosmology was initiated quite early in India, by V V Narlikar at the Banares Hindu University, and by N R Sen in Kolkata in the 1930s. In course of time, this activity grew and gained momentum, and in early 1969, at the felicitation held for the 60 years of V V Narlikar at a conference in Ahmedabad, P C Vaidya proposed the formation of the IAGRG society, with V V Narlikar being the first President. This

  8. Convocation address.

    PubMed

    Kakodkar, A

    1999-07-01

    This convocation addressed by Dr. Anil Kakodkar focuses on the challenges faced by graduating students. In his speech, he emphasized the high level of excellence achieved by the industrial sector; however, he noted that there has been a loss of initiative in maximizing value addition, which was worsened by an increasing population pressure. In facing a stiff competition in the external and domestic markets, it is imperative to maximize value addition within the country in a competitive manner and capture the highest possible market share. To achieve this, high-quality human resources are central. Likewise, family planning programs should become more effective and direct available resources toward national advantage. To boost the domestic market, he suggests the need to search for strengths to achieve leadership position in those areas. First, an insight into the relationship between the lifestyles and the needs of our people and the natural resource endowment must be gained. Second, remodeling of the education system must be undertaken to prepare the people for adding the necessary innovative content in our value addition activities. Lastly, Dr. Kakodkar emphasizes the significance of developing a strong bond between parents and children to provide a sound foundation and allow the education system to grow upon it.

  9. Opening Address

    NASA Astrophysics Data System (ADS)

    Yamada, T.

    2014-12-01

    Ladies and Gentlemen, it is my great honor and pleasure to present an opening address of the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3). On the behalf of the organizing committee, I certainly welcome all your visits to KGU Kannai Media Center belonging to Kanto Gakuin University, and stay in Yokohama. In particular, to whom come from abroad more than 17 countries, I would appreciate your participations after long long trips from your homeland to Yokohama. The first international workshop on "State of the Art in Nuclear Cluster Physics", called SOTANCP, was held in Strasbourg, France, in 2008, and the second one was held in Brussels, Belgium, in 2010. Then the third workshop is now held in Yokohama. In this period, we had the traditional 10th cluster conference in Debrecen, Hungary, in 2012. Thus we have the traditional cluster conference and SOTANCP, one after another, every two years. This obviously shows our field of nuclear cluster physics is very active and flourishing. It is for the first time in about 10 years to hold the international workshop on nuclear cluster physics in Japan, because the last cluster conference held in Japan was in Nara in 2003, about 10 years ago. The president in Nara conference was Prof. K. Ikeda, and the chairpersons were Prof. H. Horiuchi and Prof. I. Tanihata. I think, quite a lot of persons in this room had participated at the Nara conference. Since then, about ten years passed. So, this workshop has profound significance for our Japanese colleagues. The subjects of this workshop are to discuss "the state of the art in nuclear cluster physics" and also discuss the prospect of this field. In a couple of years, we saw significant progresses of this field both in theory and in experiment, which have brought better and new understandings on the clustering aspects in stable and unstable nuclei. I think, the concept of clustering has been more important than ever. This is true also in the

  10. Presidential address.

    PubMed

    Vohra, U

    1993-07-01

    The Secretary of India's Ministry of Health and Family Welfare serves as Chair of the Executive Council of the International Institute for Population Sciences in Bombay. She addressed its 35th convocation in 1993. Global population stands at 5.43 billion and increases by about 90 million people each year. 84 million of these new people are born in developing countries. India contributes 17 million new people annually. The annual population growth rate in India is about 2%. Its population size will probably surpass 1 billion by the 2000. High population growth rates are a leading obstacle to socioeconomic development in developing countries. Governments of many developing countries recognize this problem and have expanded their family planning programs to stabilize population growth. Asian countries that have done so and have completed the fertility transition include China, Japan, Singapore, South Korea, and Thailand. Burma, Malaysia, North Korea, Sri Lanka, and Vietnam have not yet completed the transition. Afghanistan, Bangladesh, Iran, Nepal, and Pakistan are half-way through the transition. High population growth rates put pressure on land by fragmenting finite land resources, increasing the number of landless laborers and unemployment, and by causing considerable rural-urban migration. All these factors bring about social stress and burden civic services. India has reduced its total fertility rate from 5.2 to 3.9 between 1971 and 1991. Some Indian states have already achieved replacement fertility. Considerable disparity in socioeconomic development exists among states and districts. For example, the states of Bihar, Madhya Pradesh, Rajasthan, and Uttar Pradesh have female literacy rates lower than 27%, while that for Kerala is 87%. Overall, infant mortality has fallen from 110 to 80 between 1981 and 1990. In Uttar Pradesh, it has fallen from 150 to 98, while it is at 17 in Kerala. India needs innovative approaches to increase contraceptive prevalence rates

  11. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Chen, Jiang; Xiao-Zhong, Guo; Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

  12. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients. PMID:28265583

  13. President's Address

    PubMed Central

    Craig, Maurice

    1928-01-01

    Conditions which experience has proved conducive to mental disturbance considered.—Suggestions as to their treatment.—A weakened inhibition, rather than any positive condition, is probably the most important factor in the production of the exhaustion psycho-neuroses or psychoses. This view is supported by the prophylactic value of giving for prolonged periods small doses of bromide to hypersensitive children or to highly-strung persons exposed to stress or tropical climate, etc.—Pavlov's work on the conditioned reflexes in dogs quoted in support of the author's clinical experience: Pavlov states that bromides should not be regarded as sedatives, diminishing the excitability of the central nervous system, but as simply regulating the nervous system by strengthening the intensity of internal inhibition. This agrees with the author's clinical experience, as small doses of bromide taken regularly over a period of many years do not diminish the mental powers but in fact increase them. Question of sleeplessness considered with regard to the way in which sedatives act. Most of these do not act as so-called “sleeping draughts”; research may ultimately show that their action is to strengthen a weakened inhibition and that sleep is only a secondary benefit.—Value of sedatives before and after surgical operation. Importance of toxæmia in the production of mental disorder; insomnia often precedes a toxic process and permits it to become active. The theory of weakened inhibition explains many problems; e.g., why certain brilliant children or adults break down and why at first there is no interference with their normal mental activity which only becomes involved as sleep and other bodily functions become affected; why a toxæmia may affect the nervous system of certain people; why a breakdown may follow over-stimulation or occur with advancing years; why some persons relapse when certain treatment is discontinued; why treatment should at times be continuous, and why

  14. Welcome Address

    NASA Astrophysics Data System (ADS)

    Kiku, H.

    2014-12-01

    Ladies and Gentlemen, It is an honor for me to present my welcome address in the 3rd International Workshop on "State of the Art in Nuclear Cluster Physics"(SOTANCP3), as the president of Kanto Gakuin University. Particularly to those from abroad more than 17 countries, I am very grateful for your participation after long long trips from your home to Yokohama. On the behalf of the Kanto Gakuin University, we certainly welcome your visit to our university and stay in Yokohama. First I would like to introduce Kanto Gakuin University briefly. Kanto Gakuin University, which is called KGU, traces its roots back to the Yokohama Baptist Seminary founded in 1884 in Yamate, Yokohama. The seminary's founder was Albert Arnold Bennett, alumnus of Brown University, who came to Japan from the United States to establish a theological seminary for cultivating and training Japanese missionaries. Now KGU is a major member of the Kanto Gakuin School Corporation, which is composed of two kindergartens, two primary schools, two junior high schools, two senior high schools as well as KGU. In this university, we have eight faculties with graduate school including Humanities, Economics, Law, Sciences and Engineering, Architecture and Environmental Design, Human and Environmental Studies, Nursing, and Law School. Over eleven thousands students are currently learning in our university. By the way, my major is the geotechnical engineering, and I belong to the faculty of Sciences and Engineering in my university. Prof. T. Yamada, here, is my colleague in the same faculty. I know that the nuclear physics is one of the most active academic fields in the world. In fact, about half of the participants, namely, more than 50 scientists, come from abroad in this conference. Moreover, I know that the nuclear physics is related to not only the other fundamental physics such as the elementary particle physics and astrophysics but also chemistry, medical sciences, medical cares, and radiation metrology

  15. A software system to collect expert relevance ratings of medical record items for specific clinical tasks.

    PubMed

    Harvey, H Benjamin; Krishnaraj, Arun; Alkasab, Tarik K

    2014-02-28

    Development of task-specific electronic medical record (EMR) searches and user interfaces has the potential to improve the efficiency and safety of health care while curbing rising costs. The development of such tools must be data-driven and guided by a strong understanding of practitioner information requirements with respect to specific clinical tasks or scenarios. To acquire this important data, this paper describes a model by which expert practitioners are leveraged to identify which components of the medical record are most relevant to a specific clinical task. We also describe the computer system that was created to efficiently implement this model of data gathering. The system extracts medical record data from the EMR of patients matching a given clinical scenario, de-identifies the data, breaks the data up into separate medical record items (eg, radiology reports, operative notes, laboratory results, etc), presents each individual medical record item to experts under the hypothetical of the given clinical scenario, and records the experts' ratings regarding the relevance of each medical record item to that specific clinical scenario or task. After an iterative process of data collection, these expert relevance ratings can then be pooled and used to design point-of-care EMR searches and user interfaces tailored to the task-specific needs of practitioners.

  16. Implementation pearls from a new guidebook on improving medication use and outcomes with clinical decision support. Effective CDS is essential for addressing healthcare performance improvement imperatives.

    PubMed

    Sirajuddin, Anwar M; Osheroff, Jerome A; Sittig, Dean F; Chuo, John; Velasco, Ferdinand; Collins, David A

    2009-01-01

    Effective clinical decision support (CDS) is essential for addressing healthcare performance improvement imperatives, but care delivery organizations (CDO) typically struggle with CDS deployment. Ensuring safe and effective medication delivery to patients is a central focus of CDO performance improvement efforts, and this article provides an overview of best-practice strategies for applying CDS to these goals. The strategies discussed are drawn from a new guidebook, co-published and co-sponsored by more than a dozen leading organizations. Developed by scores of CDS implementers and experts, the guidebook outlines key steps and success factors for applying CDS to medication management. A central thesis is that improving outcomes with CDS interventions requires that the CDS five rights be addressed successfully. That is, the interventions must deliver the right information, to the right person, in the right format, through the right channel, at the right point in workflow. This paper provides further details about these CDS five rights, and highlights other important strategies for successful CDS programs.

  17. Relationship-Specific Condom Attitudes Predict Condom Use among STD Clinic Patients with both Primary and Non-Primary Partners

    PubMed Central

    Senn, Theresa E.; Scott-Sheldon, Lori A. J.; Carey, Michael P.

    2014-01-01

    Although condom use differs by partner type (i.e., primary vs. non-primary partner), attitudes towards condom use are typically measured without consideration of partner type. This study investigated the predictive utility of condom attitudes measured separately by partner type. Participants were 270 patients (37% women, 72% Black) recruited from a publicly-funded STD clinic who reported having both primary and non-primary partners. They completed a computerized survey assessing relationship-specific condom attitudes by partner type, condom attitudes related to pleasure and respect, and condom use with primary and non-primary partners. Participants reported more positive relationship-specific condom attitudes with a non-primary vs. primary partner. When considering pleasure-related, respect-related, and relationship-specific condom attitudes simultaneously, only relationship-specific condom attitudes predicted unprotected sex, with both primary and non-primary partners. In general, pleasure and respect-related condom attitudes did not predict unprotected sex; however, pleasure-related attitudes predicted unprotected sex with a non-primary partner for men. Future research should assess relationship-specific condom attitudes. Sexual risk reduction interventions that address interpersonal consequences of condom use in both primary and non-primary relationships should be a priority. PMID:24567031

  18. Clinical and Preclinical Use of LOX-1-Specific Antibodies in Diagnostics and Therapeutics.

    PubMed

    De Siqueira, Jonathan; Abdul Zani, Izma; Russell, David A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan; Homer-Vanniasinkam, Shervanthi

    2015-11-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (SR-E1, LOX-1, OLR1) was first discovered as a vascular receptor for modified lipoprotein particles nearly 20 years ago. Since then, in vitro and in vivo studies have demonstrated an association between LOX-1, a soluble form (sLOX-1) and a number of diseases including atherosclerosis, arthritis, hypertension and pre-eclampsia. However, converting such discoveries into tools and drugs for routine clinical use is dependent on translational preclinical and clinical studies but such studies have only begun to emerge in the past decade. In this review, we identify the key clinical applications and corresponding criteria that need to be addressed for the effective use of LOX-1-related probes and molecules for patient benefit in different disease states.

  19. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis

    PubMed Central

    Feng, Yanming; Li, Jianli; Zhang, Wei; Wang, Jing; Lewis, Richard A.; Wong, Lee-Jun

    2016-01-01

    Purpose When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives. Methods We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy. Results Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42) of the unsolved cases. Conclusion Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases. PMID:27788217

  20. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies.

    PubMed

    Qazilbash, M H; Wieder, E; Thall, P F; Wang, X; Rios, R; Lu, S; Kanodia, S; Ruisaard, K E; Giralt, S A; Estey, E H; Cortes, J; Komanduri, K V; Clise-Dwyer, K; Alatrash, G; Ma, Q; Champlin, R E; Molldrem, J J

    2017-03-01

    PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.

  1. Analyzing multiple endpoints in a confirmatory randomized clinical trial-an approach that addresses stratification, missing values, baseline imbalance and multiplicity for strictly ordinal outcomes.

    PubMed

    Sun, Hengrui; Kawaguchi, Atsushi; Koch, Gary

    2017-03-01

    Confirmatory randomized clinical trials with a stratified design may have ordinal response outcomes, ie, either ordered categories or continuous determinations that are not compatible with an interval scale. Also, multiple endpoints are often collected when 1 single endpoint does not represent the overall efficacy of the treatment. In addition, random baseline imbalances and missing values can add another layer of difficulty in the analysis plan. Therefore, the development of an approach that provides a consolidated strategy to all issues collectively is essential. For a real case example that is from a clinical trial comparing a test treatment and a control for the pain management for patients with osteoarthritis, which has all aforementioned issues, multivariate Mann-Whitney estimators with stratification adjustment are applicable to the strictly ordinal responses with stratified design. Randomization based nonparametric analysis of covariance is applied to account for the possible baseline imbalances. Several approaches that handle missing values are provided. A global test followed by a closed testing procedure controls the family wise error rate in the strong sense for the analysis of multiple endpoints. Four outcomes indicating joint pain, stiffness, and functional status were analyzed collectively and also individually through the procedures. Treatment efficacy was observed in the combined endpoint as well as in the individual endpoints. The proposed approach is effective in addressing the aforementioned problems simultaneously and straightforward to implement.

  2. Commercial insurance vs community-based health plans: time for a policy option with clinical emphasis to address the cost spiral.

    PubMed

    Amundson, Bruce

    2005-01-01

    The nation continues its ceaseless struggle with the spiraling cost of health care. Previous efforts (regulation, competition, voluntary action) have included almost every strategy except clinical. Insurers have largely failed in their cost-containment efforts. There is a strong emerging body of literature that demonstrates the relationship between various clinical strategies and reductions in utilization and costs. This article describes the organization of health services, including integration of delivery and financing systems, at the community level as a model that effectively addresses the critical structural flaws that have frustrated control of costs. Community-based health plans (CHPs) have been developed and have demonstrated viability. The key elements of CHPs are a legal organizational structure, a full provider network, advanced care-management systems, and the ability to assume financial risk. Common misconceptions regarding obstacles to CHP development are the complexity of the undertaking, difficulty assuming the insurance function, and insured pools that are too small to be viable. The characteristics of successful CHPs and 2 case studies are described, including the types of advanced care-management systems that have resulted in strong financial performance. The demonstrated ability of CHPs to establish financial viability with small numbers of enrollees challenges the common assumption that there is a fixed relationship between health plan enrollment size and financial performance. Organizing the health system at the community/regional level provides an attractive alternative model in the health-reform debate. There is an opportunity for clinical systems and state and federal leaders to support the development of community-based integrated delivery and financing system models that, among other advantages, have significant potential to modulate the pernicious cost spiral.

  3. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  4. Precision autophagy: Will the next wave of selective autophagy markers and specific autophagy inhibitors feed clinical pipelines?

    PubMed

    Lebovitz, Chandra B; DeVorkin, Lindsay; Bosc, Damien; Rothe, Katharina; Singh, Jagbir; Bally, Marcel; Jiang, Xiaoyan; Young, Robert N; Lum, Julian J; Gorski, Sharon M

    2015-01-01

    Research presented at the Vancouver Autophagy Symposium (VAS) 2014 suggests that autophagy's influence on health and disease depends on tight regulation and precision targeting of substrates. Discussions recognized a pressing need for robust biomarkers that accurately assess the clinical utility of modulating autophagy in disease contexts. Biomarker discovery could flow from investigations of context-dependent triggers, sensors, and adaptors that tailor the autophagy machinery to achieve target specificity. In his keynote address, Dr. Vojo Deretic (University of New Mexico) described the discovery of a cargo receptor family that utilizes peptide motif-based cargo recognition, a mechanism that may be more precise than generic substrate tagging. The keynote by Dr. Alec Kimmelman (Harvard Medical School) emphasized that unbiased screens for novel selective autophagy factors may accelerate the development of autophagy-based therapies. Using a quantitative proteomics screen for de novo identification of autophagosome substrates in pancreatic cancer, Kimmelman's group discovered a new type of selective autophagy that regulates bioavailable iron. Additional presentations revealed novel autophagy regulators and receptors in metabolic diseases, proteinopathies, and cancer, and outlined the development of specific autophagy inhibitors and treatment regimens that combine autophagy modulation with anticancer therapies. VAS 2014 stimulated interdisciplinary discussions focused on the development of biomarkers, drugs, and preclinical models to facilitate clinical translation of key autophagy discoveries.

  5. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  6. What specifications for a centre or network of excellence in clinical research?

    PubMed

    Diebolt, Vincent; Lang, Marie; Thoby, Frédérique

    2016-02-01

    The Giens 2015 Workshop Round Table entitled "What specifications for a centre or network of excellence in clinical research?" took a viewpoint distinct from earlier work and studies on changes in clinical research activities in France. The purpose of the present work was to identify, starting from concrete examples, the main strengths and advantages of clinical research activity in France related, in part, to the background environment and also to the specific characteristics of the investigation centres considered to be among the most high-performance units in activity. The criteria retained were grouped into a set of specifications that could be used to establish a "label of excellence" upon which the different teams and clinical research centres could model themselves. It was thus considered that belonging to a centre or structured network with at least a national configuration, when this is possible for the medial topic in question, constitutes a real advantage. Four benchmarks were identified: the scientific and clinical expertise of the head investigator, as well as the qualification and operational capacity of the centre's team; definition and measurement of performance using clearly displayed indicators and evaluation procedures; the quality of the overall trial "process" and of each of its component steps; communication, because know-how and promotion go hand in hand, with the main objective of informing the professional and general public about the value of the research centre meeting the above-mentioned criteria, about its networks of competencies, and more generally, about the important assets of the background of clinical research in France. This sector of research is funded by the public authorities via calls for public grants, financial aids for structures supporting clinical research in the University Hospital Centres and other healthcare institutions allowing for a professionalization of the research occupations, and the national public health

  7. Constructing Patient Specific Clinical Trajectories from Electronic Healthcare Reimbursement Claims using Sequential Pattern Mining

    SciTech Connect

    Pullum, Laura L; Hobson, Tanner C

    2015-01-01

    We examine the use of electronic healthcare reimbursement claims (EHRC) for analyzing healthcare delivery and practice patterns across the United States (US). By analyzing over 1 billion EHRCs, we track patterns of clinical procedures administered to patients with heart disease (HD) using sequential pattern mining algorithms. Our analyses reveal that the clinical procedures performed on HD patients are highly varied leading up to and after the primary diagnosis. The discovered clinical procedure sequences reveal significant differences in the overall costs incurred across different parts of the US, indicating significant heterogeneity in treating HD patients. We show that a data-driven approach to understand patient specific clinical trajectories constructed from EHRC can provide quantitative insights into how to better manage and treat patients.

  8. Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

    PubMed

    Ma, Yunbei; Zhou, Xiao-Hua

    2017-02-01

    For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

  9. Association of immunological cell profiles with specific clinical phenotypes of scleroderma disease.

    PubMed

    López-Cacho, José Manuel; Gallardo, Soledad; Posada, Manuel; Aguerri, Miriam; Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos; Cárdaba, Blanca

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4(+) and CD8(+) T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

  10. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    PubMed Central

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  11. Prolonged elevation of serum neuron-specific enolase in children after clinical diagnosis of brain death.

    PubMed

    Suzuki, Yasuhiro; Mogami, Yukiko; Toribe, Yausihisa; Yamada, Keitaro; Yanagihara, Keiko; Hirata, Ikuko; Mano, Toshiyuki

    2012-01-01

    To elucidate the time course of neuronal cell death after the clinical criteria for brain death are met, the authors reviewed serial changes of serum neuron-specific enolase levels in 3 children (age range, 3-15 years) clinically diagnosed as brain dead due to cardiopulmonary arrest. All patients survived for more than 2 months after brain death. Children with brain death had higher peak neuron-specific enolase values (1069-2849 ng/mL) than did 3 control children (256-1800 ng/mL) who did not become brain dead but had poor neurological outcome (1 death, 2 vegetative state) after cardiopulmonary arrest. A major finding is that children with brain death showed persistent elevation of neuron-specific enolase at 4 weeks (>400 ng/mL) and 8 weeks (>50 ng/mL) after cardiopulmonary arrest, in comparison with 2 surviving patients without brain death (<50 ng/mL at 4 weeks). This prolonged elevation of neuron-specific enolase suggests that total brain necrosis might not be present at the time of clinical diagnosis of brain death.

  12. Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions.

    PubMed

    Ritt, Martin; Gaßmann, Karl-Günter; Sieber, Cornel Christian

    2016-10-01

    Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.

  13. Anomalies and specific functions in the clinical identification of defense mechanisms.

    PubMed

    Perry, J Christopher

    2014-05-01

    Standard teaching about defense mechanisms generally focuses on definitions, which do not readily aid the clinician in identifying defenses whenever individuals use them. This report demonstrates a process by which the clinician can identify when a defense is used, which ones are likely being used, and with what aim. Clinicians first notice that a defense may be operating whenever the other individual presents with anomalies in the expression of affect, behavior, speech, or its content. Some of these anomalies are described. Next, to identify the specific defense or general level of defensive functioning used, the clinician must identify the specific function of the defense in context using a process of guided clinical inference. This report examines 2 verbatim examples from recorded interviews of one case to demonstrate this process. The examples present a microcosm of clinical concerns that have a surprising relationship to the individual's course and prognosis.

  14. Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

    PubMed Central

    Halsey, Eric S.; Marks, Morgan A.; Gotuzzo, Eduardo; Fiestas, Victor; Suarez, Luis; Vargas, Jorge; Aguayo, Nicolas; Madrid, Cesar; Vimos, Carlos; Kochel, Tadeusz J.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype. Methodology and Principal Findings Between the years 2005–2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations. Conclusions/Significance Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype. PMID:22563516

  15. Current strategies and findings in clinically relevant post-translational modification-specific proteomics

    PubMed Central

    Pagel, Oliver; Loroch, Stefan; Sickmann, Albert; Zahedi, René P

    2015-01-01

    Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research. PMID:25955281

  16. Quantitative assessment of the benefits of specific information technologies applied to clinical studies in developing countries.

    PubMed

    Avilés, William; Ortega, Oscar; Kuan, Guillermina; Coloma, Josefina; Harris, Eva

    2008-02-01

    Clinical studies and trials require accessibility of large amounts of high-quality information in a timely manner, often daily. The integrated application of information technologies can greatly improve quality control as well as facilitate compliance with established standards such as Good Clinical Practice (GCP) and Good Laboratory Practice (GLP). We have customized and implemented a number of information technologies, such as personal data assistants (PDAs), geographic information system (GIS), and barcode and fingerprint scanning, to streamline a pediatric dengue cohort study in Managua, Nicaragua. Quantitative data was obtained to assess the actual contribution of each technology in relation to processing time, accuracy, real-time access to data, savings in consumable materials, and time to proficiency in training sessions. In addition to specific advantages, these information technologies benefited not only the study itself but numerous routine clinical and laboratory processes in the health center and laboratories of the Nicaraguan Ministry of Health.

  17. Untying the gordian knot: what we do and don't know about gender-specific medicine-keynote address for the 2014 Academic Emergency Medicine Consensus Conference.

    PubMed

    Legato, Marianne

    2014-12-01

    Over the past two decades, a burgeoning interest in women's health, the direct consequence of the feminist movement, has inspired a worldwide interest in the differences between the normal function of men and women and their unique experiences of the same illnesses. The scope and significance of what we have discovered and continue to find has fundamentally changed the way we prevent, diagnose, and treat diseases. Important questions remain, however, and deserve specific investigation and analysis.

  18. The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one

    PubMed Central

    Resch, Jacob E; Brown, Cathleen N; Schmidt, Julianne; Macciocchi, Stephen N; Blueitt, Damond; Cullum, C Munro; Ferrara, Michael S

    2016-01-01

    Context A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. Objective To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. Design Cross-sectional. Setting Research laboratory. Patients or other participants Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. Intervention(s) Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. Main outcome measures Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. Results Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. Conclusions Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80–100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC. PMID:27900145

  19. Assessing clinical communication skills in physicians: are the skills context specific or generalizable

    PubMed Central

    Baig, Lubna A; Violato, Claudio; Crutcher, Rodney A

    2009-01-01

    Background Communication skills are essential for physicians to practice Medicine. Evidence for the validity and domain specificity of communication skills in physicians is equivocal and requires further research. This research was conducted to adduce evidence for content and context specificity of communication skills and to assess the usefulness of a generic instrument for assessing communication skills in International Medical Graduates (IMGs). Methods A psychometric design was used for identifying the reliability and validity of the communication skills instruments used for high-stakes exams for IMG's. Data were collected from 39 IMGs (19 men – 48.7%; 20 women – 51.3%; Mean age = 41 years) assessed at 14 station OSCE and subsequently in supervised clinical practice with several instruments (patient surveys; ITERs; Mini-CEX). Results All the instruments had adequate reliability (Cronbach's alpha: .54 – .96). There were significant correlations (r range: 0.37 – 0.70, p < .05) of communication skills assessed by examiner with standardized patients, and of mini-CEX with patient surveys, and ITERs. The intra-item reliability across all cases for the 13 items was low (Cronbach's alpha: .20 – .56). The correlations of communication skills within method (e.g., OSCE or clinical practice) were significant but were non-significant between methods (e.g., OSCE and clinical practice). Conclusion The results provide evidence of context specificity of communication skills, as well as convergent and criterion-related validity of communication skills. Both in OSCEs and clinical practice, communication checklists need to be case specific, designed for content validity. PMID:19445685

  20. Three Decades of Comprehensive Geriatric Assessment: Evidence Coming From Different Healthcare Settings and Specific Clinical Conditions.

    PubMed

    Pilotto, Alberto; Cella, Alberto; Pilotto, Andrea; Daragjati, Julia; Veronese, Nicola; Musacchio, Clarissa; Mello, Anna Maria; Logroscino, Giancarlo; Padovani, Alessandro; Prete, Camilla; Panza, Francesco

    2017-02-01

    Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.

  1. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale.

    PubMed

    Neul, Jeffrey L; Glaze, Daniel G; Percy, Alan K; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E

    2015-11-01

    Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome.

  2. Addressing the question of disorder-specific risk factors of internet addiction: a comparison of personality traits in patients with addictive behaviors and comorbid internet addiction.

    PubMed

    Müller, K W; Koch, A; Dickenhorst, U; Beutel, M E; Duven, E; Wölfling, K

    2013-01-01

    Uncontrolled use of the internet has been reported to affect the lives of some users in a negative way. According to epidemiological studies, about 1% of the general population is showing signs of internet addiction. Since internet addiction is becoming a growing health concern, research on potential risk factors is becoming more important in order to develop strategies for prevention and to adopt therapeutic treatment. Although there are some studies investigating personality traits in internet addiction, most of these studies are based on samples of healthy subjects. In this research project, we compared personality profiles of a sample of patients in different rehabilitation centers. 70 patients with an addiction disorder that additionally met the criteria for internet addiction were compared to 48 patients suffering from alcohol dependence. Besides Big Five personality traits, we also assessed depressive symptoms. It was shown that patients with comorbid internet addiction can be discriminated from other patients by higher neuroticism and lower extraversion as well as lower conscientiousness. After controlling for depressive symptoms, lower conscientiousness especially turned out to be a disorder-specific risk factor. As internet addiction is related to unique patterns of personality traits and can be discriminated from alcohol dependence, treatment approaches are needed that meet the specific requirements of patients with internet addiction.

  3. Further Validation of the Female Sexual Function Index: Specificity and Associations With Clinical Interview Data.

    PubMed

    Stephenson, Kyle R; Toorabally, Nasreen; Lyons, Leah; M Meston, Cindy

    2016-07-03

    Female sexual function is a multi-faceted psychophysiological construct. The Female Sexual Function Index (FSFI) is considered a "gold standard" self-report instrument that assesses the various aspects of sexual function. However, researchers have recently proposed potential limitations of the FSFI, highlighting the need for continued validation research. The aims of the current analyses were (a) to assess the correlations between FSFI scores and information regarding specific rates of functional impairment gained via clinical interview; and (b) to assess the specificity of FSFI subscale scores in reflecting corresponding aspects of sexual function (e.g., whether the Sexual Desire subscale reflects sexual desire specifically rather than sexual arousal, orgasm, etc.). The participants were 97 sexually active women who reported impairments in sexual function. Clinical interview data exhibited moderate-to-strong correlations with FSFI scores. Additionally, FSFI subscales generally exhibited adequate specificity in terms of reflecting their corresponding aspects of sexual function more strongly than other aspects. The results generally supported the validity of the FSFI. Implications for the measurement and conceptualization of female sexual function are discussed.

  4. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity

    PubMed Central

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination. PMID:27110562

  5. A Rapid In-Clinic Test Detects Acute Leptospirosis in Dogs with High Sensitivity and Specificity.

    PubMed

    Kodjo, Angeli; Calleja, Christophe; Loenser, Michael; Lin, Dan; Lizer, Joshua

    2016-01-01

    A rapid IgM-detection immunochromatographic test (WITNESS® Lepto, Zoetis) has recently become available to identify acute canine leptospirosis at the point of care. Diagnostic sensitivity and specificity of the test were evaluated by comparison with the microscopic agglutination assay (MAT), using a positive cut-off titer of ≥800. Banked serum samples from dogs exhibiting clinical signs and suspected leptospirosis were selected to form three groups based on MAT titer: (1) positive (n = 50); (2) borderline (n = 35); and (3) negative (n = 50). Using an analysis to weight group sizes to reflect French prevalence, the sensitivity and specificity were 98% and 93.5% (88.2% unweighted), respectively. This test rapidly identifies cases of acute canine leptospirosis with high levels of sensitivity and specificity with no interference from previous vaccination.

  6. Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response.

    PubMed

    Surace, Laura; Lysenko, Veronika; Fontana, Andrea Orlando; Cecconi, Virginia; Janssen, Hans; Bicvic, Antonela; Okoniewski, Michal; Pruschy, Martin; Dummer, Reinhard; Neefjes, Jacques; Knuth, Alexander; Gupta, Anurag; van den Broek, Maries

    2015-04-21

    Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and transiently activated complement both in murine and human tumors. The local production of pro-inflammatory anaphylatoxins C3a and C5a was crucial to the tumor response to radiotherapy and concomitant stimulation of tumor-specific immunity. Dexamethasone, a drug frequently given during radiotherapy, limited complement activation and the anti-tumor effects of the immune system. Overall, our findings indicate that anaphylatoxins are key players in radiotherapy-induced tumor-specific immunity and the ensuing clinical responses.

  7. Comparison of Patient-Specific Computational Modeling Predictions and Clinical Outcomes of LASIK for Myopia

    PubMed Central

    Seven, Ibrahim; Vahdati, Ali; De Stefano, Vinicius Silbiger; Krueger, Ronald R.; Dupps, William J.

    2016-01-01

    Purpose To assess the predictive accuracy of simulation-based LASIK outcomes. Methods Preoperative and 3-month post-LASIK tomographic data from 20 eyes of 12 patients who underwent wavefront-optimized LASIK for myopia were obtained retrospectively. Patient-specific finite element models were created and case-specific treatment settings were simulated. Simulated keratometry (SimK) values and the mean tangential curvature of the central 3 mm (Kmean) were obtained from the anterior surfaces of the clinical tomographies, and computational models were compared. Correlations between Kmean prediction error and patient age, preoperative corneal hysteresis (CH), and corneal resistance factor (CRF) were assessed. Results The mean difference for Kmean between simulated and actual post-LASIK cases was not statistically significant (−0.13 ± 0.36 diopters [D], P = 0.1). The mean difference between the surgically induced clinical change in Kmean and the model-predicted change was −0.11 ± 0.34 D (P = 0.2). Kmean prediction error was correlated to CH, CRF, and patient age (r = 0.63, 0.53, and 0.5, respectively, P < 0.02), and incorporation of CH values into predictions as a linear offset increased their accuracy. Simulated changes in Kmean accounted for 97% of the variance in actual spherical equivalent refractive change. Conclusions Clinically feasible computational simulations predicted corneal curvature and manifest refraction outcomes with a level of accuracy in myopic LASIK cases that approached the limits of measurement error. Readily available preoperative biomechanical measures enhanced simulation accuracy. Patient-specific simulation may be a useful tool for clinical guidance in de novo LASIK cases. PMID:27893094

  8. Sex-Specific Clinical Correlates of Hoarding in Obsessive-Compulsive Disorder

    PubMed Central

    Samuels, Jack F.; Bienvenu, O. Joseph; Pinto, Anthony; Murphy, Dennis L.; Piacentini, John; Rauch, Scott L.; Fyer, Abby J.; Grados, Marco A.; Greenberg, Benjamin D.; Knowles, James A.; McCracken, James T.; Cullen, Bernadette; Riddle, Mark A.; Rasmussen, Steven A.; Pauls, David L.; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Pulver, Ann E.; Nestadt, Gerald

    2008-01-01

    Little is known about whether the clinical correlates of hoarding behavior are different in men and women with obsessive-compulsive disorder (OCD). In the current study, we evaluated the association of hoarding with categories of obsessions and compulsions, psychiatric disorders, personality dimensions, and other clinical characteristics separately in 151 men and 358 women with OCD who were examined during the OCD Collaborative Genetics Study. We found that, among men but not women, hoarding was associated with aggressive, sexual, and religious obsessions and checking compulsions. In men, hoarding was associated with generalized anxiety disorder and tics whereas, among women, hoarding was associated with social phobia, post-traumatic stress disorder, body dysmorphic disorder, nail biting, and skin picking. In women but not men, hoarding was associated with schizotypal and dependent personality disorder dimensions, and with low conscientiousness. These findings indicate that specific clinical correlates of hoarding in OCD are different in men and women and may reflect sex-specific differences in the course, expression, and/or etiology of hoarding behavior in OCD. PMID:18692168

  9. The use of simulation to address the acute care skills deficit in pre-registration nursing students: a clinical skill perspective.

    PubMed

    Nickless, Lesley J

    2011-05-01

    The increase in patient acuity in primary and secondary settings is continuing, with a corresponding increase in the need for technological competence in these areas. Evidence, however, both nationally and internationally, suggests that these expectations are not being met. This paper offers a review of the literature on acute care, with a specific focus on pre-registration nursing students and the development of acute care skills. Three themes are discussed: factors contributing to the acute care skills deficit, the knowledge and skills required to work in acute care and strategies used to support the acquisition of acute care skills. In response to the review, and based upon the evidence-based solutions identified, the clinical skills team at Bournemouth University designed and developed two teaching sessions, using simulation and role play to support the acquisition of acute care skills in pre-registration students. Student evaluations identify that their knowledge, competence and confidence in this area have increased following the teaching sessions, although caution remains regarding transferability of these skills into the practice environment.

  10. Personality and Defense Styles: Clinical Specificities and Predictive Factors of Alcohol Use Disorder in Women.

    PubMed

    Ribadier, Aurélien; Dorard, Géraldine; Varescon, Isabelle

    2016-01-01

    This study investigated personality traits and defense styles in order to determine clinical specificities and predictive factors of alcohol use disorders (AUDs) in women. A female sample, composed of AUD outpatients (n = 48) and a control group (n = 50), completed a sociodemographic self-report and questionnaires assessing personality traits (BFI), defense mechanisms and defense styles (DSQ-40). Comparative and correlational analyses, as well as univariate and multivariate logistic regressions, were performed. AUD women presented with higher neuroticism and lower extraversion and conscientiousness. They used less mature and more neurotic and immature defense styles than the control group. Concerning personality traits, high neuroticism and lower conscientiousness were predictive of AUD, as well as low mature, high neurotic, and immature defense styles. Including personality traits and defense styles in a logistic model, high neuroticism was the only AUD predictive factor. AUD women presented clinical specificities and predictive factors in personality traits and defense styles that must be taken into account in AUD studies. Implications for specific treatment for women are discussed.

  11. Conducting community-based, culturally specific, eye disease screening clinics for urban African Americans with diabetes.

    PubMed

    Anderson, Robert M; Wolf, Fredric M; Musch, David C; Fitzgerald, James T; Johnson, Mark W; Nwankwo, Robin B; Robins, Lynne S; Oh, Mary S; Gillard, Mary Lou

    2002-01-01

    The purpose of this study was to evaluate the need for, and efficacy of, community-based culturally specific eye disease screening clinics for urban African Americans with diabetes. The study employed a variety of culturally specific methods in the design and performance of 43 community-based eye disease screening clinics in southeastern Michigan. One thousand, thirty-seven subjects were recruited for the study. Of that number, 817 identified themselves as African Americans and are the focus of this report. Of the 817 African-American patients screened, 84 (10%) needed to be examined by an ophthalmologist immediately (< 30 days), and 180 (22%) needed to be examined soon (within 1 to 3 months), while 544 (67%) were advised to return for another exam a year later. The project demonstrated that it was possible to use culturally specific techniques to identify a significant number of urban African Americans with diabetes in need of eye screening and treatment. However, lack of health insurance proved to be the primary barrier to receiving needed treatment. Although the project was successful, it is not a solution to what is essentially a health systems problem, ie, inadequate access to appropriate diabetes care for a significant number of our population.

  12. Cancer registries in Japan: National Clinical Database and site-specific cancer registries.

    PubMed

    Anazawa, Takayuki; Miyata, Hiroaki; Gotoh, Mitsukazu

    2015-02-01

    The cancer registry is an essential part of any rational program of evidence-based cancer control. The cancer control program is required to strategize in a systematic and impartial manner and efficiently utilize limited resources. In Japan, the National Clinical Database (NCD) was launched in 2010. It is a nationwide prospective registry linked to various types of board certification systems regarding surgery. The NCD is a nationally validated database using web-based data collection software; it is risk adjusted and outcome based to improve the quality of surgical care. The NCD generalizes site-specific cancer registries by taking advantage of their excellent organizing ability. Some site-specific cancer registries, including pancreatic, breast, and liver cancer registries have already been combined with the NCD. Cooperation between the NCD and site-specific cancer registries can establish a valuable platform to develop a cancer care plan in Japan. Furthermore, the prognosis information of cancer patients arranged using population-based and hospital-based cancer registries can help in efficient data accumulation on the NCD. International collaboration between Japan and the USA has recently started and is expected to provide global benchmarking and to allow a valuable comparison of cancer treatment practices between countries using nationwide cancer registries in the future. Clinical research and evidence-based policy recommendation based on accurate data from the nationwide database may positively impact the public.

  13. Towards tract-specific fractional anisotropy (TSFA) at crossing-fiber regions with clinical diffusion MRI

    PubMed Central

    Mishra, Virendra; Guo, Xiaohu; Delgado, Mauricio R.; Huang, Hao

    2014-01-01

    Purpose White matter fractional anisotropy (FA), a measure implying microstructure, is significantly underestimated with single diffusion tensor model at crossing-fiber regions (CFR). We propose a tract-specific FA (TSFA), corrected for the effects of crossing-fiber geometry and free water at CFR, and adapted for tract analysis with diffusion MRI (dMRI) in clinical research. Methods At CFR voxels, the proposed technique estimates free water fraction (fiso) as a linear function of mean apparent diffusion coefficient (mADC), fits the dual tensors and estimates TSFA. Digital phantoms were designed for testing the accuracy of fiso and fitted dual-anisotropies at CFR. The technique was applied to clinical dMRI of normal subjects and hereditary spastic paraplegia (HSP) patients to test the effectiveness of TSFA. Results Phantom simulation showed unbiased estimates of dual-tensor anisotropies at CFR and high accuracy of fiso as a linear function of mADC. TSFA at CFR was highly consistent to the single tensor FA at non-CFR within the same tract with normal human dMRI. Additional HSP imaging biomarkers with significant correlation to clinical motor function scores could be identified with TSFA. Conclusion Results suggest the potential of the proposed technique in estimating unbiased TSFA at CFR and conducting tract analysis in clinical research. PMID:25447208

  14. USING FORMATIVE RESEARCH TO DEVELOP A CONTEXT-SPECIFIC APPROACH TO INFORMED CONSENT FOR CLINICAL TRIALS

    PubMed Central

    Corneli, Amy L.; Bentley, Margaret E.; Sorenson, James R.; Henderson, Gail E.; van der Horst, Charles; Moses, Agnes; Nkhoma, Jacqueline; Tenthani, Lyson; Ahmed, Yusuf; Heilig, Charles M.; Jamieson, Denise J.

    2009-01-01

    Participant understanding is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturally appropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-to-child transmission of HIV during breastfeeding, formative research was conducted to explore the community’s understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research. PMID:19385837

  15. Cow-specific risk factors for clinical mastitis in Brazilian dairy cattle.

    PubMed

    Oliveira, C S F; Hogeveen, H; Botelho, A M; Maia, P V; Coelho, S G; Haddad, J P A

    2015-10-01

    Information related to mastitis risk factors is useful for the design and implementation of clinical mastitis (CM) control programs. The first objective of our study was to model the risk of CM under Brazilian conditions, using cow-specific risk factors. Our second objective was to explore which risk factors were associated with the occurrence of the most common pathogens involved in Brazilian CM infections. The analyses were based on 65 months of data from 9,789 dairy cows and 12,464 CM cases. Cow-specific risk factors that could easily be measured in standard Brazilian dairy farms were used in the statistical analyses, which included logistic regression and multinomial logistic regression. The first month of lactation, high somatic cell count, rainy season and history of clinical mastitis cases were factors associated with CM for both primiparous and multiparous cows. In addition, parity and breed were also associated risk factors for multiparous cows. Of all CM cases, 54% showed positive bacteriological culturing results from which 57% were classified as environmental pathogens, with a large percentage of coliforms (35%). Coagulase-negative Staphylococcus (16%), Streptococcus uberis (9%), Streptococcus agalactiae (7%) and other Streptococci (9%) were also common pathogens. Among the pathogens analyzed, the association of cow-specific risk factors, such as Zebu breed (OR=5.84, 95%CI 3.77-10.77) and accumulated history of SCC (1.76, 95%CI 1.37-2.27), was different for CM caused by Coagulase-negative Staphylococcus and S. agalactiae in comparison to CM caused by coliforms. Our results suggest that CM control programs in Brazil should specially consider the recent history of clinical mastitis cases and the beginning of the lactations, mainly during the rainy season as important risk factor for mastitis.

  16. Clinical Experience with (18)F-Labeled Small Molecule Inhibitors of Prostate-Specific Membrane Antigen.

    PubMed

    Rowe, Steven P; Gorin, Michael A; Salas Fragomeni, Roberto A; Drzezga, Alexander; Pomper, Martin G

    2017-04-01

    Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells.

  17. Derivation of Patient Specific Pluripotent Stem Cells Using Clinically Discarded Cumulus Cells

    PubMed Central

    Xu, Jie; Lin, Chen-Ju; Wang, Sheng-Wen; Cheng, An-Sheng; Lu, Jean; Lu, Chung-Hao; Sung, Li-Ying

    2016-01-01

    Induced pluripotent stem cells (iPSCs) are powerful tools for basic and translational research, as well as regenerative medicine. In routine human in vitro fertilization (IVF) practices, cumulus cells (CCs) are discarded, representing a potential source of biological materials for regenerative medicine. In this study, we derived patient-specific iPSCs using CCs from human infertility clinics for the first time. The human cumulus cell derived iPSCs (hc-iPSCs) were characterized for growth, karyotype, expression of pluripotency genes, and were subjected to embryoid bodies (EBs) and teratoma assays to evaluate their differentiation capacity. Hc-iPSCs display typical iPSC characteristics, and are capable of differentiating into all germ layers in vitro and in vivo. We further show that putative primordial germ cell like cells (PGCLCs) can be derived using hc-iPSCs. Our data demonstrate the feasibility of deriving patient-specific pluripotent stem cells using CCs. PMID:27802323

  18. The clinical utility of pain classification in non-specific arm pain.

    PubMed

    Moloney, Niamh A; Hall, Toby M; Leaver, Andrew M; Doody, Catherine M

    2015-02-01

    Mechanisms-based pain classification has received considerable attention recently for its potential use in clinical decision making. A number of algorithms for pain classification have been proposed. Non-specific arm pain (NSAP) is a poorly defined condition, which could benefit from classification according to pain mechanisms to improve treatment selection. This study used three published classification algorithms (hereafter called NeuPSIG, Smart, Schafer) to investigate the frequency of different pain classifications in NSAP and the clinical utility of these systems in assessing NSAP. Forty people with NSAP underwent a clinical examination and quantitative sensory testing. Findings were used to classify participants according to three classification algorithms. Frequency of pain classification including number unclassified was analysed using descriptive statistics. Inter-rater agreement was analysed using kappa coefficients. NSAP was primarily classified as 'unlikely neuropathic pain' using NeuPSIG criteria, 'peripheral neuropathic pain' using the Smart classification and 'peripheral nerve sensitisation' using the Schafer algorithm. Two of the three algorithms allowed classification of all but one participant; up to 45% of participants (n = 18) were categorised as mixed by the Smart classification. Inter-rater agreement was good for the Schafer algorithm (к = 0.78) and moderate for the Smart classification (к = 0.40). A kappa value was unattainable for the NeuPSIG algorithm but agreement was high. Pain classification was achievable with high inter-rater agreement for two of the three algorithms assessed. The Smart classification may be useful but requires further direction regarding the use of clinical criteria included. The impact of adding a pain classification to clinical assessment on patient outcomes needs to be evaluated.

  19. Implementing specific oral tolerance induction to milk into routine clinical practice: experience from first 50 patients

    PubMed Central

    Luyt, David; Bravin, Kristian; Luyt, Jessica

    2014-01-01

    Background Although the natural history of cow’s milk allergy is to resolve during childhood or adolescence, a small but significant proportion of children will remain allergic. Specific oral tolerance induction to cow’s milk (CM-SOTI) provides a treatment option in these children with continuing allergy with high success rates. However current sentiment limits widespread availability as existing reports advise that it is too soon to translate CM-SOTI into routine clinical practice. Methods In January 2007 we implemented a slow up-dosing CM-SOTI program. Eligible subjects were identified at routine visits to our children’s allergy clinic. Persisting cow’s milk allergy was confirmed from recent contact symptoms or a positive baked milk challenge. As allergic symptoms are common during CM-SOTI, families were provided with ready dietetic access for advice on dosing and symptom treatment. Subjects were continuously monitored at subsequent clinic visits or telephonically, where no longer followed, for a median of 49 months. Results The first 50 subjects (35 males) treated ranged in age from 5.1 to 15.8 years (median 10.3 years). Full tolerance (250 mL) was achieved in 23 subjects, 9 without any symptoms, and a further 9 achieved partial tolerance with continued ingestion. Eighteen children failed to achieve any regular milk ingestion; 11 because of persistent or significant symptoms whilst 8 withdrew against medical advice. Allergic symptoms were predominantly mild to moderate in severity, although 2 cases needed treatment with inhaled salbutamol and a further 2 required intramuscular adrenaline. Clinical tolerance, both full and partial, persists beyond 5 years. Conclusion We have demonstrated that a CM-SOTI program can be successfully and safely implemented as routine clinical practice with acceptable compliance during prolonged home up-dosing, despite frequent allergic symptoms, and for up to 4 years after starting treatment. CM-SOTI can thus be put into

  20. Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

    PubMed

    Merlo, Giulia; Clapasson, Andrea; Cozzani, Emanuele; Sanna, Luigi; Pesce, Giampaola; Bagnasco, Marcello; Burlando, Martina; Parodi, Aurora

    2017-03-01

    Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

  1. Task-specific writing tremor: clinical phenotypes, progression, treatment outcomes, and proposed nomenclature.

    PubMed

    Ondo, William G; Satija, Pankaj

    2012-02-01

    Task-specific tremor diagnoses remain controversial. We evaluated 56 subjects seen with writing tremor. The diagnosis was made if there was a clear history of exclusive tremor while writing for at least 3 years before noticing tremor in any other scenario and the continued presence of writing tremor as the most prominent aspect of their tremor disorder on examination. The age of tremor onset was 47.2 ± 18.0 years (73.2% male). Ethnic backgrounds were Caucasian (68.4%), African (23.2%), Hispanic (5.2%), and Asian/Indian (3.3%), and 44% reported any tremor in a first degree relative. Writing tremor often progressed to other task-specific tremors or rest tremor but not to immediate postural tremor, as usually seen in essential tremor. The other tremor provoking scenarios were eating/drinking (14), brushing teeth/shaving/make-up (5), typing (2), suture removal (1), and drafting (1) and occurred a mean of 7.5 years after the onset of writing tremor. Fourteen developed a "rest" (true rest or crescendo) tremor but only 2 of these met clinical criteria for Parkinson's disease. Pharmacologic treatments of writing tremor, including with ethanol, were generally poor, whereas deep brain stimulation of the ventral intermediate (VIM) thalamus was successful. Compared with patients with "classic" essential tremor in our clinic, writing tremor patients were more likely African, more likely male, had an older age of onset, a lower likelihood of familial tremor, and were more refractory to tremor medications and ethanol. This supports segregation between task-specific tremor and essential tremor but does not support the specific diagnosis of "writing tremor" because many patients progress to tremor with other tasks.

  2. Clinical anxiety, cortisol and interleukin-6: Evidence for specificity in emotion–biology relationships

    PubMed Central

    O'Donovan, Aoife; Hughes, Brian M.; Slavich, George M.; Lynch, Lydia; Cronin, Marie-Therese; O'Farrelly, Cliona; Malone, Kevin M.

    2015-01-01

    Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases. PMID:20227485

  3. Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report.

    PubMed

    Pajno, Giovanni Battista; Bernardini, Roberto; Peroni, Diego; Arasi, Stefania; Martelli, Alberto; Landi, Massimo; Passalacqua, Giovanni; Muraro, Antonella; La Grutta, Stefania; Fiocchi, Alessandro; Indinnimeo, Luciana; Caffarelli, Carlo; Calamelli, Elisabetta; Comberiati, Pasquale; Duse, Marzia

    2017-01-23

    Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3-5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers' preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.

  4. Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms.

    PubMed

    Levison, L J; Miller-Cushon, E K; Tucker, A L; Bergeron, R; Leslie, K E; Barkema, H W; DeVries, T J

    2016-02-01

    Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000 cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM.

  5. Impact of donor-specific antibodies on the outcomes of kidney graft: Pathophysiology, clinical, therapy

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2014-01-01

    Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donor-specific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens (HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the post-transplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage. These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase I-II of clinical trials. Thus the pipeline for the near future appears almost empty. PMID:24669363

  6. Formative evaluation of a patient-specific clinical knowledge summarization tool

    PubMed Central

    Del Fiol, Guilherme; Mostafa, Javed; Pu, Dongqiuye; Medlin, Richard; Slager, Stacey; Jonnalagadda, Siddhartha R.; Weir, Charlene R.

    2015-01-01

    Objective To iteratively design a prototype of a computerized clinical knowledge summarization (CKS) tool aimed at helping clinicians finding answers to their clinical questions; and to conduct a formative assessment of the usability, usefulness, efficiency, and impact of the CKS prototype on physicians’ perceived decision quality compared with standard search of UpToDate and PubMed. Materials and methods Mixed-methods observations of the interactions of 10 physicians with the CKS prototype vs. standard search in an effort to solve clinical problems posed as case vignettes. Results The CKS tool automatically summarizes patient-specific and actionable clinical recommendations from PubMed (high quality randomized controlled trials and systematic reviews) and UpToDate. Two thirds of the study participants completed 15 out of 17 usability tasks. The median time to task completion was less than 10 s for 12 of the 17 tasks. The difference in search time between the CKS and standard search was not significant (median = 4.9 vs. 4.5 min). Physician’s perceived decision quality was significantly higher with the CKS than with manual search (mean = 16.6 vs. 14.4; p = 0.036). Conclusions The CKS prototype was well-accepted by physicians both in terms of usability and usefulness. Physicians perceived better decision quality with the CKS prototype compared to standard search of PubMed and UpToDate within a similar search time. Due to the formative nature of this study and a small sample size, conclusions regarding efficiency and efficacy are exploratory. PMID:26612774

  7. Trade-offs in producing patient-specific recommendations from a computer-based clinical guideline: a case study.

    PubMed Central

    Miller, P L; Frawley, S J

    1995-01-01

    This case study explored 1) how much online clinical data is required to obtain patient-specific recommendations from a computer-based clinical practice guideline, 2) whether the availability of increasing amounts of online clinical data might allow a higher specificity of those recommendations, and 3) whether that increased specificity is necessarily desirable. The "quick reference guide" version of the guideline for acute postoperative pain management in adults, developed by the Agency for Health Care Policy and Research, was analyzed. Patient-specific data items that might be used to tailor the computer's output for a particular case were grouped into rough categories depending on how likely they were to be available online and how readily they might be determined from online clinical data. The patient-specific recommendations were analyzed to determine to what degree the amount of text produced depended on the online availability of different categories of data. An examination of example recommendations, however, illustrated that high specificity may not always be desirable. The study provides a concrete illustration of how the richness of online clinical data can affect patient-specific recommendations, and describes a number of related design trade-offs in converting a clinical guideline into an interactive, computer-based form. PMID:7583647

  8. The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations

    PubMed Central

    Alabdali, Majed; Alsulaiman, Abdulla; Albulaihe, Hana; Breiner, Ari; Katzberg, Hans D.; Aljaafari, Danah; Lovblom, Leif E.; Bril, Vera

    2017-01-01

    Introduction Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be

  9. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications

    PubMed Central

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  10. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis.

    PubMed

    Volz, Magdalena Sarah; Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-12-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4(+) T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4(+) T cells. The production of inflammatory cytokines such as TNF-α by CD4(+) T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.

  11. Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

    PubMed Central

    2014-01-01

    SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology

  12. The Differences in Clinical Aspect Between Specific Language Impairment and Global Developmental Delay

    PubMed Central

    Kim, Seong Woo; Jeon, Ha Ra; Chung, Hee Jung; Song, Jung Eun

    2014-01-01

    Objective To compare and analyze the clinical characteristics of children with delayed language acquisition due to two different diagnoses, which were specific language impairment (SLI, a primarily delayed language development) and global developmental delay (GDD, a language delay related to cognitive impairment). Methods Among 1,598 children who had visited the developmental delay clinic from March 2005 to February 2011, 467 children who were diagnosed with GDD and 183 children who were diagnosed with SLI were included in this study. All children were questioned about past, family, and developmental history, and their language competences and cognitive function were assessed. Some children got electroencephalography (EEG), in case of need. Results The presence of the perinatal risk factors showed no difference in two groups. In the children with GDD, they had more delayed acquisition of independent walking and more frequent EEG abnormalities compared with the children with SLI (p<0.01). The positive family history of delayed language development was more prevalent in children with SLI (p<0.01). In areas of language ability, the quotient of receptive language and expressive language did not show any meaningful statistical differences between the two groups. Analyzing in each group, the receptive language quotient was higher than expressive language quotient in both group (p<0.01). In the GDD group, the Bayley Scales of Infant Development II (BSID-II) showed a marked low mental and motor quotient while the Wechsler Intelligence Scale showed low verbal and nonverbal IQ. In the SLI group, the BSID-II and Wechsler Intelligence Scale showed low scores in mental area and verbal IQ but sparing motor area and nonverbal IQ. Conclusion The linguistic profiles of children with language delay could not differentiate between SLI and GDD. The clinicians needed to be aware of these developmental issues, and history taking and clinical evaluation, including cognitive assessment

  13. The effects of specific educational preparation on emergency nurses' clinical decisions regarding supplemental oxygen administration.

    PubMed

    Considine, Julie; Botti, Mari; Thomas, Shane

    2006-06-01

    The use of supplemental oxygen by emergency nurses has important implications for patient outcomes, yet there is significant variability in oxygen administration practises. Specific education related to oxygen administration increases factual knowledge in this domain; however, the impact of knowledge acquisition on nurses' clinical decisions is poorly understood. This study aimed to examine the effect of educational preparation on 20 emergency nurses' decisions regarding the assessment of oxygenation and the use of supplemental oxygen. A pre-test/post-test, quasi-experimental design was used. The intervention was a written, self-directed learning package. The major effects of the completion of the learning package included no change in the number or types of parameters used by nurses to assess oxygenation, a significant decrease in the selection of simple masks, a significant increase in the selection of air entrainment masks, fewer hypothetical outcomes of unresolved respiratory distress and more hypothetical outcomes of decreased respiratory distress. As many nursing education programs are aimed at increasing factual knowledge, while experience remains relatively constant, a greater understanding of the relationship between factual knowledge and clinical decisions is needed if educational interventions are to improve patient outcomes.

  14. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management.

    PubMed

    Aksglaede, Lise; Link, Katarina; Giwercman, Aleksander; Jørgensen, Niels; Skakkebaek, Niels E; Juul, Anders

    2013-02-15

    47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from "near-normal" to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under-diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age-specific recommendations for medical management. © 2013 Wiley Periodicals, Inc.

  15. The Specificity of Emotional Switching in Borderline Personality Disorder in Comparison to Other Clinical Groups

    PubMed Central

    Houben, Marlies; Bohus, Martin; Santangelo, Philip; Ebner-Priemer, Ulrich; Trull, Timothy; Kuppens, Peter

    2016-01-01

    In an attempt to better understand the nature of emotion dysregulation in the daily lives of persons with a borderline personality disorder (BPD), Houben, Vansteelandt et al. (2015) recently identified emotional switching, which refers to the tendency to make large changes between positive and negative emotional states over time, as a possible defining characteristic of the emotion dynamics observed in BPD. The goal of this study was to examine the specificity of these previous findings in two samples, by comparing BPD patients (N = 43 in sample 1; N = 81 in sample 2) to patients with bulimia nervosa (N = 20) or posttraumatic stress disorder (N = 28) or healthy controls (N = 28) in sample 1, and to patients with depressive disorder (N = 50) in sample 2, with respect to measures of emotional switching. Analyses of these two experience sampling datasets revealed that contrary to expectations, BPD patients did not differ from the clinical groups regarding their mere tendency to switch between positive and negative emotional states on consecutive moments over time, and regarding the magnitude of such changes between positive and negative emotional states over time. However, all clinical groups did differ from healthy controls regarding all switch measures in dataset 1. These results indicate that emotional switching, similar to other more traditional indicators of overall changes in emotional intensity in daily life, might reflect a feature of emotional responding characterising a range of disorders with mood disturbances. PMID:26882282

  16. Intuitive presentation of clinical forensic data using anonymous and person-specific 3D reference manikins.

    PubMed

    Urschler, Martin; Höller, Johannes; Bornik, Alexander; Paul, Tobias; Giretzlehner, Michael; Bischof, Horst; Yen, Kathrin; Scheurer, Eva

    2014-08-01

    The increasing use of CT/MR devices in forensic analysis motivates the need to present forensic findings from different sources in an intuitive reference visualization, with the aim of combining 3D volumetric images along with digital photographs of external findings into a 3D computer graphics model. This model allows a comprehensive presentation of forensic findings in court and enables comparative evaluation studies correlating data sources. The goal of this work was to investigate different methods to generate anonymous and patient-specific 3D models which may be used as reference visualizations. The issue of registering 3D volumetric as well as 2D photographic data to such 3D models is addressed to provide an intuitive context for injury documentation from arbitrary modalities. We present an image processing and visualization work-flow, discuss the major parts of this work-flow, compare the different investigated reference models, and show a number of cases studies that underline the suitability of the proposed work-flow for presenting forensically relevant information in 3D visualizations.

  17. The National Neurosurgery Quality and Outcomes Database Qualified Clinical Data Registry: 2015 measure specifications and rationale.

    PubMed

    Parker, Scott L; McGirt, Matthew J; Bekelis, Kimon; Holland, Christopher M; Davies, Jason; Devin, Clinton J; Atkins, Tyler; Knightly, Jack; Groman, Rachel; Zyung, Irene; Asher, Anthony L

    2015-12-01

    Meaningful quality measurement and public reporting have the potential to facilitate targeted outcome improvement, practice-based learning, shared decision making, and effective resource utilization. Recent developments in national quality reporting programs, such as the Centers for Medicare & Medicaid Services Qualified Clinical Data Registry (QCDR) reporting option, have enhanced the ability of specialty groups to develop relevant quality measures of the care they deliver. QCDRs will complete the collection and submission of Physician Quality Reporting System (PQRS) quality measures data on behalf of individual eligible professionals. The National Neurosurgery Quality and Outcomes Database (N(2)QOD) offers 21 non-PQRS measures, initially focused on spine procedures, which are the first specialty-specific measures for neurosurgery. Securing QCDR status for N(2)QOD is a tremendously important accomplishment for our specialty. This program will ensure that data collected through our registries and used for PQRS is meaningful for neurosurgeons, related spine care practitioners, their patients, and other stakeholders. The 2015 N(2)QOD QCDR is further evidence of neurosurgery's commitment to substantively advancing the health care quality paradigm. The following manuscript outlines the measures now approved for use in the 2015 N(2)QOD QCDR. Measure specifications (measure type and descriptions, related measures, if any, as well as relevant National Quality Strategy domain[s]) along with rationale are provided for each measure.

  18. Holoprosencephaly and ZIC2 microdeletions: novel clinical and epidemiological specificities delineated.

    PubMed

    Chabchoub, E; Willekens, D; Vermeesch, J R; Fryns, J-P

    2012-06-01

    Holoprosencephaly (HPE), the most common malformation of the human brain results from abnormal cleavage of the forebrain during the early embryonic developmental stages. The spectrum of malformations in HPE is wide, ranging from the classical cyclopia/proboscis to fairly asymptomatic forms [i.e. a single maxillary central incisor (SMCI)]. HPE may be caused by environmental or genetic factors. ZIC2 (13q32) was the second gene identified in which mutations cause HPE and recently a specific phenotype was ascribed to ZIC2-mutation HPE. Earlier, we reported a boy presenting HPE and deafness. Cytogenetic analyses were normal. Using array-comparative genomic hybridization (aCGH), we found a de novo 129 kb del(13)(q32) encompassing ZIC2 and ZIC5. There is no evidence for the involvement of ZIC5 in human diseases. We reviewed the literature for ZIC2-ZIC5 deletions and their involvement in neural tube defects (NTDs). Interestingly, we found evidence for a specific facial phenotype for ZIC2 gene deletion patients distinct from those with point mutations. In addition, based on the clinical data together with pathology, imaging and functional studies, we suggest an outline for a model explaining the genetic heterogeneity of ZIC2-ZIC5-associated NTDs and propose further studies for validation.

  19. Clinical research: up from 'clinical epidemiology'.

    PubMed

    Miettinen, Olli S; Bachmann, Lucas M; Steurer, Johann

    2009-12-01

    Clinical research must be understood to be the foundation of scientific medicine of the clinical type. But the essence of scientific clinical medicine remains a matter of profound confusion, even in clinical academia, and so does the essence of clinical research. The confusion now revolves, principally, around 'clinical epidemiology'. We address clinical research in the meaning of quintessentially 'applied' clinical research, which we take to be the foundation of the scientific knowledge base of clinical medicine, of gnosis (dia-, etio-, pro-) in it. More specifically, we address the essence, priorities, and status quo of this research - and argue that the requisite theory of this is not a matter of 'clinical epidemiology' but of theory of clinical research endogenous to clinical (rather than epidemiological) academia.

  20. Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies.

    PubMed

    Bache, M; Kappler, M; Said, H M; Staab, A; Vordermark, D

    2008-01-01

    Poor oxygenation of solid tumors is a major indicator of adverse prognosis after standard treatment, e.g. radiotherapy. This observation founded on intratumoral pO(2) electrode measurements has been supported more recently by studies of injected hypoxia markers (pimonidazole, EF5) or hypoxia-related proteins (hypoxia-inducible factor-1alpha, carbonic anhydrase IX) detected immunohistochemically. Alternative approaches include imaging of tumor hypoxia by nuclear medicine studies and the measurement of hypoxia-related proteins (osteopontin) in patient plasma. Low oxygen levels as found in tumors are rarely observed in normal tissues. The presence of hypoxic tumor cells is therefore regarded not only as an adverse prognostic factor but as an opportunity for tumor-specific treatment. Classic approaches to normalize tumor oxygenation involve the breathing of modified gas mixtures and pharmacologic modification of blood flow as in the "accelerated radiotherapy, carbogen, nicotinamide" (ARCON) scheme. Specific killing of hypoxic tumor cells can potentially be achieved by hypoxia-selective cytotoxins (model substance tirapazamine), which has shown promise in head and neck cancer. Direct targeting of hypoxia-related molecules such as hypoxia-inducible factor-1alpha, the central regulator of the hypoxic response in tumor cells, is an attractive approach currently tested in preclinical models. For clinical applications, the appropriate combination of hypoxia detection for patient selection with a hypoxia-specific treatment is essential. A therapeutic benefit has been suggested for the selection of patients by plasma osteopontin level and treatment with the hypoxic radiosensitizer nimorazole in addition to radiotherapy, for selection by F-misonidazole positron-emission tomography (PET) and treatment with tirapazamine in addition to chemoradiation and for selection by pimonidazole immunohistochemistry and ARCON treatment, all in head and neck cancer.

  1. Commercial Insurance vs Community-Based Health Plans: Time for a Policy Option With Clinical Emphasis to Address the Cost Spiral

    ERIC Educational Resources Information Center

    Amundson, Bruce

    2005-01-01

    The nation continues its ceaseless struggle with the spiraling cost of health care. Previous efforts (regulation, competition, voluntary action) have included almost every strategy except clinical. Insurers have largely failed in their cost-containment efforts. There is a strong emerging body of literature that demonstrates the relationship…

  2. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, Josh; Levy, Saul; Smith, D.; Wei, S.; Miyake, K.; Murdocca, M.

    1991-01-01

    The progress on the Rutgers CAM (Content Addressable Memory) Project is described. The overall design of the system is completed at the architectural level and described. The machine is composed of two kinds of cells: (1) the CAM cells which include both memory and processor, and support local processing within each cell; and (2) the tree cells, which have smaller instruction set, and provide global processing over the CAM cells. A parameterized design of the basic CAM cell is completed. Progress was made on the final specification of the CPS. The machine architecture was driven by the design of algorithms whose requirements are reflected in the resulted instruction set(s). A few of these algorithms are described.

  3. A scalable architecture for incremental specification and maintenance of procedural and declarative clinical decision-support knowledge.

    PubMed

    Hatsek, Avner; Shahar, Yuval; Taieb-Maimon, Meirav; Shalom, Erez; Klimov, Denis; Lunenfeld, Eitan

    2010-01-01

    Clinical guidelines have been shown to improve the quality of medical care and to reduce its costs. However, most guidelines exist in a free-text representation and, without automation, are not sufficiently accessible to clinicians at the point of care. A prerequisite for automated guideline application is a machine-comprehensible representation of the guidelines. In this study, we designed and implemented a scalable architecture to support medical experts and knowledge engineers in specifying and maintaining the procedural and declarative aspects of clinical guideline knowledge, resulting in a machine comprehensible representation. The new framework significantly extends our previous work on the Digital electronic Guidelines Library (DeGeL) The current study designed and implemented a graphical framework for specification of declarative and procedural clinical knowledge, Gesher. We performed three different experiments to evaluate the functionality and usability of the major aspects of the new framework: Specification of procedural clinical knowledge, specification of declarative clinical knowledge, and exploration of a given clinical guideline. The subjects included clinicians and knowledge engineers (overall, 27 participants). The evaluations indicated high levels of completeness and correctness of the guideline specification process by both the clinicians and the knowledge engineers, although the best results, in the case of declarative-knowledge specification, were achieved by teams including a clinician and a knowledge engineer. The usability scores were high as well, although the clinicians' assessment was significantly lower than the assessment of the knowledge engineers.

  4. Address tracing for parallel machines

    NASA Technical Reports Server (NTRS)

    Stunkel, Craig B.; Janssens, Bob; Fuchs, W. Kent

    1991-01-01

    Recently implemented parallel system address-tracing methods based on several metrics are surveyed. The issues specific to collection of traces for both shared and distributed memory parallel computers are highlighted. Five general categories of address-trace collection methods are examined: hardware-captured, interrupt-based, simulation-based, altered microcode-based, and instrumented program-based traces. The problems unique to shared memory and distributed memory multiprocessors are examined separately.

  5. The sensitivity and specificity of F-DOPA PET in a movement disorder clinic

    PubMed Central

    Ibrahim, Nevein; Kusmirek, Joanna; Struck, Aaron F; Floberg, John M; Perlman, Scott B; Gallagher, Catherine; Hall, Lance T

    2016-01-01

    Idiopathic Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with nigral degeneration or striatal dopamine deficiency. Therefore, the early clinical diagnosis alone may not be accurate and this reinforces the importance of functional imaging targeting the pathophysiology of the disease process. 18F-DOPA L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the monoaminergic disturbances in PD. In this study, we aim to illustrate our local experience to determine the accuracy of 18F-DOPA PET for diagnosis of PD. We studied a total of 27 patients. A retrospective analysis was carried out for all patients that underwent 18F-DOPA PET brain scan for motor symptoms suspicious for PD between 2001-2008. Both qualitative and semi-quantitative analyses of the scans were performed. The patient’s medical records were then assessed for length of follow-up, response to levodopa, clinical course of illness, and laterality of symptoms at time of 18F-DOPA PET. The eventual diagnosis by the referring neurologist, movement disorder specialist, was used as the reference standard for further analysis. Of the 28 scans, we found that one was a false negative, 20 were true positives, and 7 were true negatives. The resultant values are Sensitivity 95.4% (95% CI: 100%-75.3%), Specificity 100% (95% CI: 100%-59.0%), PPV 100% (95% CI 100%-80.7%), and NPV 87.5% (95% CI: 99.5%-50.5%). PMID:27069770

  6. Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

    PubMed

    Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

    2016-02-01

    We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy.

  7. Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis

    PubMed Central

    Webb, Jadon R.; Addington, Jean; Perkins, Diana O.; Bearden, Carrie E.; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; Heinssen, Robert K.; Seidman, Larry J.; Tarbox, Sarah I.; Tsuang, Ming T.; Walker, Elaine F.; McGlashan, Thomas H.; Woods, Scott W.

    2015-01-01

    It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2–45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis. PMID:26272875

  8. [Gender medicine. Sex- and gender-specific aspects of clinical medicine].

    PubMed

    Kautzky-Willer, A

    2014-09-01

    Gender medicine studies sex- and gender-based differences in the development and prevention of diseases, the awareness and presentation of symptoms, and the effectiveness of therapy. Gender medicine is part of personalized medicine, considering differences in biological and psychosocial factors individually. There are differences in genes, chromosomes, hormones, and metabolism as well as differences in culture, environment, and society. Lifelong interactions between physical and psychosocial factors will influence the health and ill-health of men and women in different ways. Epigenetic modifications provide evidence of the impact of environment and lifestyle during vulnerable phases on biological processes, effecting future generations. Maternal lifestyle and environmental factors during pregnancy can impact the health of offspring in later life already in utero in a sex-specific way. Pain, stress, and coping styles differ between men and women. Women experience more dramatic physical changes during their lifetime, which are associated with specific burdens and psychosocial alterations. Women with multiple roles and responsibilities suffering from stress develop depression more frequently. However, men are often not diagnosed and treated appropriately in cases of depression or osteoporosis, diseases that are typically considered "female." There are prominent differences between men and women in medicine regarding the immune system, inflammation, and noncommunicable diseases such as obesity, type 2 diabetes, hypertension, and cardiovascular disease. Women experience more often autoimmune diseases and suffer more frequently from (chronic) pain, neurodegenerative changes, and functional disabilities. Men have shorter life expectancy but relatively more healthy years of life, which is in greater part ascribed to psychosocial determinants. State-of-the-art clinical medicine comprises individual risk factors based on sex- and gender-sensitive health programs in order to

  9. Clinical optimization of antigen specific modulation of type 1 diabetes with the plasmid DNA platform.

    PubMed

    Gottlieb, Peter; Utz, Paul J; Robinson, William; Steinman, Lawrence

    2013-12-01

    Some clinical trials in humans have aimed at modulation of type 1 diabetes (T1D) via alteration of the immune response to putative islet cell antigens, particularly proinsulin and insulin, glutamic acid decarboxylase and the peptide, DiaPep 277, derived from heat shock protein 60. The focus here is on development of a specially engineered DNA plasmid encoding proinsulin to treat T1D. The plasmid is engineered to turn off adaptive immunity to proinsulin. This approach yielded exciting results in a randomized placebo controlled trial in 80 adult patients with T1D. The implications of this trial are explored in regards to the potential for sparing inflammation in islets and thus allowing the functioning beta cells to recover and produce more insulin. Strategies to further strengthen the effects seen thus far with the tolerizing DNA plasmid to proinsulin will be elucidated. The DNA platform affords an opportunity for easy modifications. In addition standard exploration of dose levels, route of administration and frequency of dose are practical. Optimization of the effects seen to date on C-peptide and on depletion of proinsulin specific CD8 T cells are feasible, with expected concomitant improvement in other parameters like hemoglobin A1c and reduction in insulin usage. T1D is one of the few autoimmune conditions where antigen specific therapy can be achieved, provided the approach is tested intelligently. Tolerizing DNA vaccines to proinsulin and other islet cell autoantigens is a worthy pursuit to potentially treat, prevent and to perhaps even 'cure' or 'prevent' type 1 diabetes.

  10. Specific clinical manifestations of Nocardia: A case report and literature review

    PubMed Central

    Yu, Songsong; Wang, Jing; Fang, Qiuhong; Zhang, Jixin; Yan, Fengcai

    2016-01-01

    Nocardiosis is a rare bacterial infection of either the lungs (pulmonary) or body (systemic) that usually affects immunocompromised individuals. It is caused by Gram-positive, aerobic actinomycetes of the Nocardia genus. Multiple high-density sheet shadows in both lungs along with nodules or cavities are the most common presentations of nocardiosis, whereas a large pulmonary mass is considered to be rare. However, there is no specificity in the clinical manifestation of the disease. Therefore, isolation and identification of Nocardia strains is the only reliable diagnostic method. The present study describes the cases of two male patients of Asian descent with nocardiosis. Chest computed tomography scans showed a suspected tumor mass in both patients. Microscopic analysis and culturing of tissue samples obtained using a bronchoscope detected the presence of Nocardia wallacei. Neither patient showed signs of immunosuppression. The present study aimed to improve the understanding of lung nocardiosis and demonstrated that pulmonary nocardiosis should be suspected in the case of non-immunocompromised patients with a large mass in the lung. Furthermore, a review of the literature on infection with Nocardia was conducted. PMID:27698688

  11. [Clinical evaluation of calcium-polycarbophil in the treatment of non-specific diarrhea].

    PubMed

    Gizzi, G; Villani, V; Rubinetto, M P; Cianci, M; La Froscia, A; Barbara, L

    1993-09-01

    We performed a study on 10 patients aged between 26 and 54 males and females, affected by non-specific diarrhea. A single-blind clinical trial has been developed where Calcium-Polycarbophil was administered (2 cps t.i.d.) for a period of 8 weeks, half with placebo and half with drug in cross-over. No drop-out occurred. Number of evaluations, cramps and consistency of stools, have been evaluated before and after treatment. A definite decrease of evacuations per day and of cramps, when present, together with a higher consistency of stools, are reported when Calcium-Polycarbophil is administered, according to the favourable medical judgement. Haematochemical parameters, evaluated before, during and after the treatment didn't show any relevant variation, apart from slight increase (not statistically significant) of calcium both in blood and in urine). No other unwanted event has been detected. Hence, the high therapeutic index of Calcium-Polycarbophil makes it highly desirable in the treatment of diarrhea.

  12. Clinical evaluation of an anatomy-based patient specific quality assurance system.

    PubMed

    Hauri, Pascal; Verlaan, Sarah; Graydon, Shaun; Ahnen, Linda; Klöck, Stephan; Lang, Stephanie

    2014-03-06

    The Delta(4DVH) Anatomy 3D quality assurance (QA) system (ScandiDos), which converts the measured detector dose into the dose distribution in the patient geometry was evaluated. It allows a direct comparison of the calculated 3D dose with the measured back-projected dose. In total, 16 static and 16 volumetric-modulated arc therapy (VMAT) fields were planned using four different energies. Isocenter dose was measured with a pinpoint chamber in homogeneous phantoms to investigate the dose prediction by the Delta(4DVH) Anatomy algorithm for static fields. Dose distributions of VMAT fields were measured using GAFCHROMIC film. Gravitational gantry errors up to 10° were introduced into all VMAT plans to study the potential of detecting errors. Additionally, 20 clinical treatment plans were verified. For static fields, the Delta(4DVH) Anatomy predicted the isocenter dose accurately, with a deviation to the measured phantom dose of 1.1% ± 0.6%. For VMAT fields the predicted Delta(4DVH) Anatomy dose in the isocenter plane corresponded to the measured dose in the phantom, with an average gamma agreement index (GAI) (3 mm/3%) of 96.9± 0.4%. The Delta(4DVH) Anatomy detected the induced systematic gantry error of 10° with a relative GAI (3 mm/3%) change of 5.8% ± 1.6%. The conventional Delta(4PT) QA system detected a GAI change of 4.2%± 2.0%. The conventional Delta(4PT) GAI (3 mm/3%) was 99.8% ± 0.4% for the clinical treatment plans. The mean body and PTV-GAI (3 mm/5%) for the Delta(4DVH) Anatomy were 96.4% ± 2.0% and 97.7%± 1.8%; however, this dropped to 90.8%± 3.4% and 87.1% ± 4.1% for passing criteria of 3 mm/3%. The anatomy-based patient specific quality assurance system predicts the dose distribution correctly for a homogeneous case. The limiting factor for the error detection is the large variability in the error-free plans. The dose calculation algorithm is inferior to that used in the TPS (Eclipse).

  13. Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows.

    PubMed

    Hertl, J A; Schukken, Y H; Welcome, F L; Tauer, L W; Gröhn, Y T

    2014-03-01

    The objective of this study was to estimate the effects of clinical mastitis (CM) cases due to different pathogens on milk yield in Holstein cows. The first 3 CM cases in a cow's lactation were modeled. Eight categories of pathogens were included: Streptococcus spp.; Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level detectable by our microbiological procedures) observed in the culture sample, and cases with contamination (≥ 3 pathogens in the sample); other pathogens that may be treated with antibiotics (included Citrobacter, Corynebacterium bovis, Enterobacter, Enterococcus, Pasteurella, Pseudomonas; "other treatable"); and other pathogens not successfully treated with antibiotics (Trueperella pyogenes, Mycoplasma, Prototheca, yeasts; "other not treatable"). Data from 38,276 lactations in cows from 5 New York State dairy herds, collected from 2003-2004 until 2011, were analyzed. Mixed models with an autoregressive correlation structure (to account for correlation among the repeated measures of milk yield within a lactation) were estimated. Primiparous (lactation 1) and multiparous (lactations 2 and 3) cows were analyzed separately, as the shapes of their lactation curves differed. Primiparas were followed for up to 48 wk of lactation and multiparas for up to 44 wk. Fixed effects included parity, calving season, week of lactation, CM (type, case number, and timing of CM in relation to milk production cycle), and other diseases (milk fever, retained placenta, metritis, ketosis, displaced abomasum). Herd was modeled as a random effect. Clinical mastitis was more common in multiparas than in primiparas. In primiparas, Streptococcus spp. occurred most frequently as the first case. In multiparas, E. coli was most common as the first case. In subsequent cases, CM cases with no specific growth or contamination were most common in both parity groups. The hazard of

  14. Addressing the shortage of health professionals in South Africa through the development of a new cadre of health worker: the creation of Clinical Associates.

    PubMed

    Couper, Ian D; Hugo, Jannie F M

    2014-01-01

    South Africa made a decision in 2002 to develop so-called mid-level medical workers, now known as clinical associates. This article describes the background to this decision, and the national process of developing the profession and its scope of practice, which was aligned with the needs of the health service, particularly those of rural district hospitals. A common national curriculum was then developed, with implementation in three faculties. The first graduates have entered the profession, starting in 2011, and are in the process of establishing themselves across the country. They are already making an important contribution to rural health care, and are seeking ways in which the profession can be enhanced to ensure sustainability. The profession needs to adapt itself to the changing realities of the South African context.

  15. Addressing Health Disparities among Men: Demographic, Behavioral and Clinical Characteristics of Men who have Sex with Men Living in Puerto Rico

    PubMed Central

    Colón-López, Vivian; Soto-Salgado, Marievelisse; Rodríguez-Díaz, Carlos; Suárez, Erick L.; Pérez, Cynthia M.

    2013-01-01

    The objective of this study was to compare sociodemographic, behavioral and clinical characteristics associated with HIV among Men who have sex with Men (MSM) and men who have sex with women (MSW) in Puerto Rico. Data from a population-based cross-sectional study in PR (2005–2008) was analyzed. Descriptive statistics were used to describe the study sample and bivariate analyses were performed to identify differences of sociodemographic, behavioral and clinical characteristics between MSM and MSW. Exact logistic regression models adjusting for age were constructed for each risk behavior associated to MSM in bivariate analysis. Of the 674 men interviewed, 6.1% (n=41) reported ever having sex with men. Age-adjusted logistic regression models indicated that MSM were significantly more likely than MSW to have first sexual intercourse before the age of 15 (POR=2.6; 95%CI= 1.3, 5.3) and have at least 10 lifetime sex partners (POR=2.8; 95%CI= 1.4,5.9). Also, MSM were significantly more likely to report lifetime use of marihuana (POR=2.7; 95%CI= 1.3,5.8), cocaine (POR=2.5; 95%CI= 1.2,5.0), amphetamines (POR=3.8; 95%CI= 1.4,9.2) and sedatives or tranquilizers (POR=3.3; 95%CI= 1.4,7.2). Also, MSM were 13 times more likely to be HIV seropositive as compared to MSW (POR=13.3; 95%CI=1.7,102.0). In this population-based sample of men living in Puerto Rico, self-reported same-sex behavior is strongly associated with HIV, and other behavioral factors associated with HIV. Future targeted research is still necessary for the development of intervention programs among MSM in Puerto Rico. PMID:24288521

  16. Critical differences in HIV-1 and HIV-2 protease specificity for clinical inhibitors

    SciTech Connect

    Tie, Yunfeng; Wang, Yuan-Fang; Boross, Peter I.; Chiu, Ting-Yi; Ghosh, Arun K.; Tozser, Jozsef; Louis, John M.; Harrison, Robert W.; Weber, Irene T.

    2012-03-15

    Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR{sub 2}) than on HIV-1 protease (PR{sub 1}). We solved the crystal structure of PR{sub 2} with APV at 1.5 {angstrom} resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR{sub 1} mutant (PR{sub 1M}) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR{sub 2}. PR{sub 1M} more closely resembled PR{sub 2} than PR{sub 1} in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR{sub 1M} with APV, DRV, and SQV were compared with available PR{sub 1} and PR{sub 2} complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR{sub 1M} and PR{sub 1}, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR{sub 1M}. Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR{sub 1M} and PR{sub 2} relative to the strong hydrogen bonds observed in PR{sub 1}, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR{sub 1M} partially replicates the specificity of PR{sub 2} and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.

  17. The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

    PubMed

    Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

    2013-10-25

    Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses.

  18. Genus Level Identification of Mycobacteria from Clinical Specimens by Using an Easy-To-Handle Mycobacterium-Specific PCR Assay

    PubMed Central

    Stauffer, Fritz; Haber, Heinrich; Rieger, Armin; Mutschlechner, Robert; Hasenberger, Petra; Tevere, Vincent J.; Young, Karen K. Y.

    1998-01-01

    An easy-to-handle Mycobacterium-specific PCR assay for detection of the presence of a wide range of mycobacterial species in clinical samples was evaluated. The performance of the genus probe was compared with the performance of probes specific for Mycobacterium tuberculosis and Mycobacterium avium and with that of standard culture. In addition, the utility of an internal control in monitoring amplification inhibitors was studied. Of 545 respiratory and 325 nonrespiratory specimens (a total of 870 specimens), 58 (6.7%) showed the presence of amplification inhibitors, as determined by a negative result for the internal control. Of these 58 specimens, 31 (53%) were stool specimens; other material, even citrate blood after lysis of erythrocytes, did not pose a problem with regard to inhibition of PCR amplification. Eighty-one of the remaining 812 specimens had a positive Mycobacterium culture result. Of these culture-positive specimens, 58 (71.6%) showed a positive result with the Mycobacterium genus-specific probe. Seventy-two samples had a positive result with the Mycobacterium-specific probe but a negative culture result. Of these 72 samples, 26 samples were regarded as true positive, either because the M. tuberculosis- or M. avium-specific probe was also positive at the same time or because other specimens from the same patient taken at the same time were culture positive. The sensitivity of the Mycobacterium-specific probe was 78.5% and the specificity was 93.5%. This study showed that pretesting of clinical specimens for mycobacteria to the genus level with a Mycobacterium-specific probe offers the routine clinical laboratory the possibility of detecting tuberculous and nontuberculous mycobacteria with one test. Furthermore, specimens testing positive with the genus-specific probe can be immediately identified with species-specific probes. PMID:9508282

  19. A collaborative clinical and population-based curriculum for medical students to address primary care needs of the homeless in New York City shelters : Teaching homeless healthcare to medical students.

    PubMed

    Asgary, Ramin; Naderi, Ramesh; Gaughran, Margaret; Sckell, Blanca

    2016-06-01

    Background Millions of Americans experience homelessness annually. Medical providers do not receive adequate training in primary care of the homeless.Methods Starting in 2012, a comprehensive curriculum was offered to medical students during their family medicine or ambulatory clerkship, covering clinical, social and advocacy, population-based, and policy aspects. Students were taught to: elicit specific social history, explore health expectations, and assess barriers to healthcare; evaluate clinical conditions specific to the homeless and develop plans for care tailored toward patients' medical and social needs; collaborate with shelter staff and community organizations to improve disease management and engage in advocacy efforts. A mixed methods design was used to evaluate students' knowledge, attitudes, and skills including pre- and post-curriculum surveys, debriefing sessions, and observed clinical skills.Results The mean age of the students (n = 30) was 26.5 years; 55 % were female. The overall scores improved significantly in knowledge, attitude, and self-efficacy domains using paired t‑test (p < 0.01). Specific skills in evaluating mental health, substance abuse, and risky behaviours improved significantly (p < 0.05). In evaluation of communication skills, the majority were rated as having 'outstanding rapport with patients.'Conclusions Comprehensive and ongoing clinical component in shelter clinics, complementary teaching, experienced faculty, and working relationship and collaboration with community organizations were key elements.

  20. [Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

    PubMed

    Bachmann, H

    1987-11-01

    Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

  1. The Asgaard project: a task-specific framework for the application and critiquing of time-oriented clinical guidelines.

    PubMed

    Shahar, Y; Miksch, S; Johnson, P

    1998-01-01

    Clinical guidelines can be viewed as generic skeletal-plan schemata that represent clinical procedural knowledge and that are instantiated and refined dynamically by care providers over significant time periods. In the Asgaard project, we are investigating a set of tasks that support the application of clinical guidelines by a care provider other than the guideline's designer. We are focusing on the application of the guideline, recognition of care providers' intentions from their actions, and critique of care providers' actions given the guideline and the patient's medical record. We are developing methods that perform these tasks in multiple clinical domains, given an instance of a properly represented clinical guideline and an electronic medical patient record. In this paper, we point out the precise domain-specific knowledge required by each method, such as the explicit intentions of the guideline designer (represented as temporal patterns to be achieved or avoided). We present a machine-readable language, called Asbru, to represent and to annotate guidelines based on the task-specific ontology. We also introduce an automated tool for the acquisition of clinical guidelines based on the same ontology, developed using the PROTEGE-II framework.

  2. The correlation between anti phospholipase A2 specific IgE and clinical symptoms after a bee sting in beekeepers

    PubMed Central

    Matysiak, Joanna; Bręborowicz, Anna; Dereziński, Paweł; Kokot, Zenon J.

    2016-01-01

    Introduction Beekeepers are a group of people with high exposure to honeybee stings and with a very high risk of allergy to bee venom. Therefore, they are a proper population to study the correlations between clinical symptoms and results of diagnostic tests. Aim The primary aim of our study was to assess the correlations between total IgE, venom- and phospholipase A2-specific IgE and clinical symptoms after a bee sting in beekeepers. The secondary aim was to compare the results of diagnostic tests in beekeepers and in individuals with standard exposure to bees. Material and methods Fifty-four individuals were divided into two groups: beekeepers and control group. The levels of total IgE (tIgE), venom-specific IgE (venom sIgE), and phospholipase A2-specific IgE (phospholipase A2 sIgE) were analyzed. Results Our study showed no statistically significant correlation between the clinical symptoms after a sting and tIgE in the entire analyzed group. There was also no correlation between venom sIgE level and clinical symptoms either in beekeepers or in the group with standard exposure to bees. We observed a statistically significant correlation between phospholipase A2 sIgE level and clinical signs after a sting in the group of beekeepers, whereas no such correlation was detected in the control group. Significantly higher venom-specific IgE levels in the beekeepers, as compared to control individuals were shown. Conclusions In beekeepers, the severity of clinical symptoms after a bee sting correlated better with phospholipase A2 sIgE than with venom sIgE levels. PMID:27512356

  3. Evaluation of Luminex xTAG fungal analyte-specific reagents for rapid identification of clinically relevant fungi.

    PubMed

    Babady, N Esther; Miranda, Edwin; Gilhuley, Kathleen A

    2011-11-01

    Invasive fungal infections (IFI) remain a serious threat to immunocompromised hosts. Current diagnostic methods, including fungal culture and antigen detection, are slow and often lack specificity. Rapid diagnostic tools with increased sensitivity and specificity could improve the care of patients with IFI. Recently, Luminex Molecular Diagnostics (Toronto, Canada) developed 23 analyte-specific reagents (ASRs) for the detection of the most common clinically relevant fungi. This study's objective was to evaluate the sensitivity and specificity of a subset of these ASRs for fungal isolates and clinical specimens. Previously characterized fungal and bacterial isolates (n = 110), blood culture specimens (n = 34), and respiratory specimens (n = 44) were tested using either a Candida 7-plex panel (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Candida guilliermondii, and Candida krusei) or a mold 11-plex panel (Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium oxysporum/Fusarium solani, Rhizopus arrhizus, Rhizopus microsporus, Mucor indicus, and Cunninghamella bertholletiae). The Candida 7-plex panel correctly identified all Candida isolates as confirmed by fungal culture and biochemical tests, for a sensitivity and specificity of 100%. The mold 11-plex panel correctly identified all mold isolates tested except for A. niger. Fungal isolates of Rhizopus and Mucor species were not detected, either, although they could represent species other than those targeted by the ASRs. Further evaluation will be necessary to confirm the sensitivities of some of the mold ASRs. Implementation of these ASRs will allow same-day detection of fungal DNA in clinical specimens.

  4. Dye dilution proliferation assay: application of the DDPA to identify tumor-specific T cell precursor frequencies in clinical trials.

    PubMed

    Schwaab, Thomas; Fisher, Jan L; Meehan, Kenneth R; Fadul, Camilo E; Givan, Alice L; Ernstoff, Marc S

    2007-01-01

    A better understanding of immune effector and regulatory pathways has led to innovative, and complex, immunotherapy strategies. CD8(+) cytolytic T lymphocytes (CTL) provide one common pathway of tumor cell destruction. The peripheral blood CTL compartment typically comprises a minority of anti-tumor CD8(+) lymphocytes and the determination of their number during clinical trials is the focus of various laboratory methods. We have monitored tumor specific CD8(+) as well as CD4(+) lymphocyte precursor frequencies in the peripheral blood using a Dye Dilution Proliferation Assay (DDPA). We summarize our experience applying DDPA in a multi-parameter, antigen-specific assay, detailing some of its complexities and advantages. We provide examples of our clinical trial results showing tumor-specific CD8(+) and CD4(+) precursor frequency (PF) data in patients being treated on novel immunotherapy trials.

  5. Correction factors for ionization chamber dosimetry in CyberKnife: Machine-specific, plan-class, and clinical fields

    SciTech Connect

    Gago-Arias, Araceli; Antolin, Elena; Fayos-Ferrer, Francisco; Simon, Rocio; Gonzalez-Castano, Diego M.; Palmans, Hugo; Sharpe, Peter; Gomez, Faustino; Pardo-Montero, Juan

    2013-01-15

    Purpose: The aim of this work is the application of the formalism for ionization chamber reference dosimetry of small and nonstandard fields [R. Alfonso, P. Andreo, R. Capote, M. S. Huq, W. Kilby, P. Kjaell, T. R. Mackie, H. Palmans, K. Rosser, J. Seuntjens, W. Ullrich, and S. Vatnitsky, 'A new formalism for reference dosimetry of small and nonstandard fields,' Med. Phys. 35, 5179-5186 (2008)] to the CyberKnife robotic radiosurgery system. Correction factors for intermediate calibration fields, a machine-specific reference field (msr) and two plan-class specific reference fields (pcsr), have been studied. Furthermore, the applicability of the new formalism to clinical dosimetry has been analyzed through the investigation of two clinical treatments. Methods: PTW31014 and Scanditronix-Wellhofer CC13 ionization chamber measurements were performed for the fields under investigation. Absorbed dose to water was determined using alanine reference dosimetry, and experimental correction factors were calculated from alanine to ionization chamber readings ratios. In addition, correction factors were calculated for the intermediate calibration fields and one of the clinical treatment fields using the Monte Carlo method and these were compared with the experimental values. Results: Overall correction factors deviating from unity by approximately 2% were obtained from both measurements and simulations, with values below and above unity for the studied intermediate calibration fields and clinical fields for the ionization chambers under consideration. Monte Carlo simulations yielded correction factors comparable with those obtained from measurements for the machine-specific reference field, although differences from 1% to 3.3% were observed between measured and calculated correction factors for the composite intermediate calibration fields. Dose distribution inhomogeneities are thought to be responsible for such discrepancies. Conclusions: The differences found between overall

  6. Scleroderma: the role of serum autoantibodies in defining specific clinical phenotypes and organ system involvement

    PubMed Central

    Domsic, Robyn T.

    2014-01-01

    Purpose of review To discuss recent advances in serologic testing for SSc-associated antibodies with respect to the diagnosis and prognosis of the disease. Recent findings The importance of SSc antibodies for diagnosis has become increasingly recognized, as evidence by incorporation into the 2013 ACR/EULAR clinical classification criteria for SSc. Two new SSc-associated antibodies and their clinical associations have been described. Multiple cohort studies have reported variable antibody frequency distribution based on geography, but the clinical associations remain much the same. New associations include anti-RNA polymerase III antibodies with gastric antral vascular ectasia, and a temporal association between SSc onset and RNA polymerase III antibodies. Summary The role and associations of SSc-associated antibodies for diagnosis and internal organ involvement is becoming increasingly accepted. PMID:25203118

  7. Multisite artery disease: a common and challenging clinical condition calling for specific management.

    PubMed

    Di Noi, Paola; Brancati, Marta Francesca; Burzotta, Francesco; Trani, Carlo

    2014-05-01

    'Multisite' artery disease is defined as the simultaneous presence of clinically significant atherosclerotic lesions in at least two major vascular territories. The management of patients with multisite artery disease represents a common challenge in clinical practice, since they are at increased risk for both vascular and coronary surgery. Preliminary experiences suggest that percutaneous treatment may represent a promising strategy for patients with multisite artery disease. In this review, the prevalence and management of multisite artery disease are discussed with particular attention to coronary and peripheral revascularization related issues.

  8. [Selected clinical and laboratory tests during specific immunotherapy of patients hypersensitive to insect bites].

    PubMed

    Szymański, W; Kazberuk, M; Michalska, I; Chyrek-Borowska, S

    The study aimed at determining selected immunologic parameters of the cellular histamine secretion and skin reactivity in the group of 9 patients hypersensitive to insect poison with effective immunotherapy following 2 years of maintenance treatment. It has been shown that the continuation of the specific immunotherapy for 2 years maintains and even increases favourable changes in humoral and cellular immunity induced already in the early phase of desensitization. An assay of the specific IgE and IgG4, cellular histamine secretion, and skin reactivity is of value in monitoring specific allergy to insect poison immunotherapy.

  9. Addressing Ozone Layer Depletion

    EPA Pesticide Factsheets

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  10. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  11. Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain

    PubMed Central

    Apkarian, A.V.; Hashmi, J.A.; Baliki, M.N.

    2010-01-01

    We review recent advances in brain imaging in humans, concentrating on advances in our understanding of the human brain in clinical chronic pain. Understanding regarding anatomical and functional reorganization of the brain in chronic pain is emphasized. We conclude by proposing a brain model for the transition of the human from acute to chronic pain. PMID:21146929

  12. The Development of English as a Second Language with and without Specific Language Impairment: Clinical Implications

    ERIC Educational Resources Information Center

    Paradis, Johanne

    2016-01-01

    Purpose: The purpose of this research forum article is to provide an overview of typical and atypical development of English as a second language (L2) and to present strategies for clinical assessment with English language learners (ELLs). Method: A review of studies examining the lexical, morphological, narrative, and verbal memory abilities of…

  13. Verb Morphology as Clinical Marker of Specific Language Impairment: Evidence from First and Second Language Learners

    ERIC Educational Resources Information Center

    Verhoeven, Ludo; Steenge, Judit; van Balkom, Hans

    2011-01-01

    The goal of this study was to search for verb morphology characteristics as possible clinical markers of SLI in Dutch as a first and second language. We also wanted to find out to what extent bilingual children with SLI are additionally disadvantaged in comparison to monolingual children with SLI, on the one hand, and to typically developing…

  14. Specific bronchial reactivity to toluene diisocyanate: relationship with baseline clinical findings.

    PubMed Central

    Paggiaro, P L; Innocenti, A; Bacci, E; Rossi, O; Talini, D

    1986-01-01

    One hundred and fourteen subjects with asthma induced by toluene diisocyanate were identified and the pattern of their bronchial responses to challenge with toluene diisocyanate was studied. An occupational type specific bronchial provocation test with toluene diisocyanate (10-25 parts per thousand million for 10-15 minutes) elicited an immediate response in 24, a late response in 50, and a dual response in 40 patients. Subjects with a dual response showed at diagnosis a longer duration of symptoms and a greater prevalence of airway obstruction; in these subjects FEV1 (percentage of predicted value) was lower than in subjects with immediate or late reactions to toluene diisocyanate. The percentage of current smokers and ex-smokers was significantly lower in subjects with a late response (26%) than in subjects with immediate or dual responses (56% and 57% respectively). In 27 of the 114 subjects a non-specific challenge test with methacholine was performed and subjects with dual responses showed greater non-specific bronchial hyperresponsiveness than the other groups. These results suggest that a dual response to specific challenge in bronchial asthma related to toluene diisocyanate may be associated with more severe disease than other types of response, as assessed by duration of symptoms, baseline airway obstruction, and non-specific bronchial hyperresponsiveness. The high prevalence of non-smokers and low prevalence of smokers in the group with a late response to specific challenge is so far unexplained. PMID:3016938

  15. Detection of Clostridium tetani in human clinical samples using tetX specific primers targeting the neurotoxin.

    PubMed

    Ganesh, Madhu; Sheikh, Nasira K; Shah, Pooja; Mehetre, Gajanan; Dharne, Mahesh S; Nagoba, Basavraj S

    2016-01-01

    Tetanus resulting from ear injury remains an important health problem, particularly in the developing world. We report the successful detection of Clostridium tetani using tetX specific primers targeting the Cl. tetani neurotoxin. The sample was obtained from an ear discharge of a case of otogenic tetanus in a 2-year-old male child. Based on the culture results of the ear discharge, Gram staining and virulence testing by genotyping, a diagnosis of tetanus was confirmed. This is the first report from India on the successful detection of Cl. tetani in a human clinical sample using tetX specific primers targeting the Cl. tetani neurotoxin.

  16. Identification of Mycobacterium bovis in bovine clinical samples by PCR species-specific primers.

    PubMed Central

    Romero, R E; Garzón, D L; Mejía, G A; Monroy, W; Patarroyo, M E; Murillo, L A

    1999-01-01

    Tuberculosis, caused by Mycobacterium bovis is emerging as the most important disease affecting cattle. Furthermore, it results in a major public health problem when transmitted to humans. Due to its difficult and non-specific diagnosis, M. bovis has been declared to be one of the etiologic agents causing significant economic loss in the cattle industry. Our group evaluated a more rapid and specific method, based on a new polymerase chain reaction species-specific primers, which amplifies a 470-base pair fragment of the M. bovis genome. A total of 275 milk-producing cows were studied by intradermal tuberculin test (ITT) which gave 184 positive and 91 negative cases. From them, 50 animals were taken from a cattle ranch free of tuberculosis. Three different samples were collected from each animal (blood, nasal mucus, and milk). Positive results were obtained from 26 animals by PCR (11.4%), 1 by bacteriological culturing (0.4%) and 1 by bacilloscopy (0.4%). This finding suggests, as in previous reports, that ITT, normally used for bovine tuberculosis detection, has the inconvenience of having a broad range of specificity and sensitivity, and the PCR technique is a more specific and sensitive test to detect infection associated with M. bovis. Therefore, we propose this PCR assay as a useful tool in the epidemiological characterization of infected animals in areas considered to be at high risk of transmission. Images Figure 1. PMID:10369566

  17. Identification of uterine leiomyoma-specific marker genes based on DNA methylation and their clinical application

    PubMed Central

    Sato, Shun; Maekawa, Ryo; Yamagata, Yoshiaki; Tamura, Isao; Lee, Lifa; Okada, Maki; Jozaki, Kosuke; Asada, Hiromi; Tamura, Hiroshi; Sugino, Norihiro

    2016-01-01

    Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to determine whether the uterus can be retained. Therefore, biomarkers for uterine leiomyomas, and reliable and objective diagnostic methods have been desired besides the pathological diagnosis. In the present study, we identified 12 genes specific to uterine leiomyomas based on DNA methylation. Using these marker genes specific to uterine leiomyomas, we established a hierarchical clustering system based on the DNA methylation level of the marker genes, which could completely differentiate between uterine leiomyomas and normal myometrium. Furthermore, our hierarchical clustering system completely discriminated uterine cancers and differentiated between uterine leiomyosarcomas and leiomyomas with more than 70% accuracy. In conclusion, this study identified DNA methylation-based marker genes specific to uterine leiomyomas, and our hierarchical clustering system using these marker genes was useful for differential diagnosis of uterine leiomyomas and leiomyosarcomas. PMID:27498619

  18. Development and Validation of Burkholderia pseudomallei-Specific Real-Time PCR Assays for Clinical, Environmental or Forensic Detection Applications

    PubMed Central

    Price, Erin P.; Dale, Julia L.; Cook, James M.; Sarovich, Derek S.; Seymour, Meagan L.; Ginther, Jennifer L.; Kaufman, Emily L.; Beckstrom-Sternberg, Stephen M.; Mayo, Mark; Kaestli, Mirjam; Glass, Mindy B.; Gee, Jay E.; Wuthiekanun, Vanaporn; Warner, Jeffrey M.; Baker, Anthony; Foster, Jeffrey T.; Tan, Patrick; Tuanyok, Apichai; Limmathurotsakul, Direk; Peacock, Sharon J.; Currie, Bart J.; Wagner, David M.; Keim, Paul; Pearson, Talima

    2012-01-01

    The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. Species-specific PCR assays provide a technically simple method for differentiating B. pseudomallei from near-neighbor species. However, substantial genetic diversity and high levels of recombination within this species reduce the likelihood that molecular signatures will differentiate all B. pseudomallei from other Burkholderiaceae. Currently available molecular assays for B. pseudomallei detection lack rigorous validation across large in silico datasets and isolate collections to test for specificity, and none have been subjected to stringent quality control criteria (accuracy, precision, selectivity, limit of quantitation (LoQ), limit of detection (LoD), linearity, ruggedness and robustness) to determine their suitability for environmental, clinical or forensic investigations. In this study, we developed two novel B. pseudomallei specific assays, 122018 and 266152, using a dual-probe approach to differentiate B. pseudomallei from B. thailandensis, B. oklahomensis and B. thailandensis-like species; other species failed to amplify. Species specificity was validated across a large DNA panel (>2,300 samples) comprising Burkholderia spp. and non-Burkholderia bacterial and fungal species of clinical and environmental relevance. Comparison of assay specificity to two previously published B. pseudomallei-specific assays, BurkDiff and TTS1, demonstrated comparable performance of all assays, providing between 99.7 and 100% specificity against our isolate panel. Last, we subjected 122018 and 266152 to rigorous quality control analyses, thus providing quantitative limits of assay performance. Using B. pseudomallei as a model, our study provides a framework for comprehensive quantitative validation of molecular assays and provides additional, highly validated B. pseudomallei assays for the scientific research community. PMID:22624061

  19. Development and validation of Burkholderia pseudomallei-specific real-time PCR assays for clinical, environmental or forensic detection applications.

    PubMed

    Price, Erin P; Dale, Julia L; Cook, James M; Sarovich, Derek S; Seymour, Meagan L; Ginther, Jennifer L; Kaufman, Emily L; Beckstrom-Sternberg, Stephen M; Mayo, Mark; Kaestli, Mirjam; Glass, Mindy B; Gee, Jay E; Wuthiekanun, Vanaporn; Warner, Jeffrey M; Baker, Anthony; Foster, Jeffrey T; Tan, Patrick; Tuanyok, Apichai; Limmathurotsakul, Direk; Peacock, Sharon J; Currie, Bart J; Wagner, David M; Keim, Paul; Pearson, Talima

    2012-01-01

    The bacterium Burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. Species-specific PCR assays provide a technically simple method for differentiating B. pseudomallei from near-neighbor species. However, substantial genetic diversity and high levels of recombination within this species reduce the likelihood that molecular signatures will differentiate all B. pseudomallei from other Burkholderiaceae. Currently available molecular assays for B. pseudomallei detection lack rigorous validation across large in silico datasets and isolate collections to test for specificity, and none have been subjected to stringent quality control criteria (accuracy, precision, selectivity, limit of quantitation (LoQ), limit of detection (LoD), linearity, ruggedness and robustness) to determine their suitability for environmental, clinical or forensic investigations. In this study, we developed two novel B. pseudomallei specific assays, 122018 and 266152, using a dual-probe approach to differentiate B. pseudomallei from B. thailandensis, B. oklahomensis and B. thailandensis-like species; other species failed to amplify. Species specificity was validated across a large DNA panel (>2,300 samples) comprising Burkholderia spp. and non-Burkholderia bacterial and fungal species of clinical and environmental relevance. Comparison of assay specificity to two previously published B. pseudomallei-specific assays, BurkDiff and TTS1, demonstrated comparable performance of all assays, providing between 99.7 and 100% specificity against our isolate panel. Last, we subjected 122018 and 266152 to rigorous quality control analyses, thus providing quantitative limits of assay performance. Using B. pseudomallei as a model, our study provides a framework for comprehensive quantitative validation of molecular assays and provides additional, highly validated B. pseudomallei assays for the scientific research community.

  20. Predicting Early Spelling Difficulties in Children with Specific Language Impairment: A Clinical Perspective

    ERIC Educational Resources Information Center

    Cordewener, Kim A. H.; Bosman, Anna M. T.; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in the Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered…

  1. An audit of prostate-specific antigen and clinical symptoms in general practice.

    PubMed Central

    Ramachandran, S.; Foster, M. C.; Thomas, D. R.; Roalfe, A. K.; Hall, R. A.

    1998-01-01

    The objective was to devise local guidelines for the referral of patients with suspected prostatic carcinoma following evaluation by a retrospective audit of the value of the prostate-specific antigen concentration, together with age, urological symptoms, and digital rectal examination in the diagnosis of carcinoma of the prostate. Relevant details were collected from the notes of 582 patients from general practice and hospital. The significant diagnostic factors were ascertained by stepwise logistic regression. Prostate-specific antigen concentration, digital rectal examination and significant terminal dribbling were the most powerful factors in the diagnosis of carcinoma of the prostate. When prostate-specific antigen concentration was considered in isolation, a value of 6.5 ng/ml appeared appropriate for referral. Age was not significant, perhaps due to the narrow patient age range. The significant diagnostic factors were built into an algorithm calculating the probability of carcinoma of the prostate. This algorithm, together with prostate-specific antigen concentration results and digital rectal examination findings, forms the basis of the referral guidelines and a subsequent prospective study. PMID:9538483

  2. Adiposity in children and adolescents: Correlates and clinical consequences of fat stored in specific body depots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on...

  3. Dynamics of Leishmania-specific immunoglobulin isotypes in dogs with clinical leishmaniasis before and after treatment.

    PubMed

    Rodríguez, Alhelí; Solano-Gallego, Laia; Ojeda, Ana; Quintana, Josefina; Riera, Cristina; Gállego, Montserrat; Portús, Montserrat; Alberola, Jordi

    2006-01-01

    Concentrations of Leishmania-specific immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) isotypes were analyzed by enzyme-linked immunosorbent assay (ELISA) in 23 dogs naturally infected with Leishmania infantum before and 1 year after initiating drug therapy. Results showed a high expression and prevalence of Leishmania-specific IgG (176.4 +/- 89 ELISA units [EU]), IgM (105.3 +/- 95.5 EU), and IgA (153.6 +/- 98 EU) in dogs before treatment (median +/- interquartile range EU). One year after treatment was started, dogs were classified as responsive dogs (RDs; n = 13) or unresponsive dogs (UDs; n = 10) based on clinicopathologic findings. Both groups of dogs experienced a statistically significant decrease (P < .05) in Leishmania-specific IgG (RDs = 27%, UDs = 41%), IgM (RDs = 42%, UDs = 29%), and IgA (RDs = 56%, UDs = 46%). Concentrations of specific IgG and IgM were not different at diagnosis or after treatment between the 2 groups. However, the median value for Leishmania-specific IgA 1 year after treatment was significantly lower (P < .05) in RDs (60.8 +/- 67 EU) than in UDs (117 +/- 54 EU). Examination of our data indicates that both the IgA isotype, which is mostly produced by mucosal plasma cells, and the IgM isotype are increased in infected symptomatic dogs, as previously reported for IgG. These 3 isotypes decreased significantly 1 year after initiation of medical treatment.

  4. Mutant allele specific imbalance in oncogenes with copy number alterations: Occurrence, mechanisms, and potential clinical implications.

    PubMed

    Yu, Chih-Chieh; Qiu, Wanglong; Juang, Caroline S; Mansukhani, Mahesh M; Halmos, Balazs; Su, Gloria H

    2017-01-01

    Mutant allele specific imbalance (MASI) was initially coined to describe copy number alterations associated with the mutant allele of an oncogene. The copy number gain (CNG) specific to the mutant allele can be readily observed in electropherograms. With the development of genome-wide analyses at base-pair resolution with copy number counts, we can now further differentiate MASI into those with CNG, with copy neutral alteration (also termed acquired uniparental disomy; UPD), or with loss of heterozygosity (LOH) due to the loss of the wild-type (WT) allele. Here we summarize the occurrence of MASI with CNG, aUPD, or MASI with LOH in some major oncogenes (such as EGFR, KRAS, PIK3CA, and BRAF). We also discuss how these various classifications of MASI have been demonstrated to impact tumorigenesis, progression, metastasis, prognosis, and potentially therapeutic responses in cancer, notably in lung, colorectal, and pancreatic cancers.

  5. Limitations of sensitivity, specificity, likelihood ratio, and bayes' theorem in assessing diagnostic probabilities: a clinical example.

    PubMed

    Moons, K G; van Es, G A; Deckers, J W; Habbema, J D; Grobbee, D E

    1997-01-01

    We evaluated the extent to which the sensitivity, specificity, and likelihood ratio of the exercise test to diagnose coronary artery disease vary across subgroups of a certain patient population. Among 295 patients suspected of coronary artery disease, as independently determined by coronary angiography, we assessed variation in sensitivity and specificity according to patient history, physical examination, exercise test results, and disease severity in 207 patients with and 88 patients without coronary artery disease, respectively. The sensitivity varied substantially according to sex (women 30% and men 64%), systolic blood pressure at baseline (53% to 65%), expected workload (50% to 64%), systolic blood pressure at peak exercise (50% to 67%), relative workload (33% to 68%), and number of diseased vessels (39% to 77%). The specificity varied across subgroups of sex (men 89% and women 97%) and relative workload (85% to 98%). The likelihood ratio varied (3.8 to 17.0) across the same patient subgroups, as did the sensitivity. As each population tends to be heterogeneous with respect to patient characteristics, no single level of these parameters can be given that is adequate for all subgroups. Use of these parameters as a basis for calculating diagnostic probabilities in individual patients using Bayes' theorem has serious limitations.

  6. Addressing Social Issues.

    ERIC Educational Resources Information Center

    Schoebel, Susan

    1991-01-01

    Maintains that advertising can help people become more aware of social responsibilities. Describes a successful nationwide newspaper advertising competition for college students in which ads address social issues such as literacy, drugs, teen suicide, and teen pregnancy. Notes how the ads have helped grassroots programs throughout the United…

  7. Invitational Addresses, 1965.

    ERIC Educational Resources Information Center

    Gates, Arthur I.; And Others

    The full texts of invitational addresses given at the 1965 International Reading Association (IRA) Convention in Detroit, Michigan, by six recipients of IRA citation awards are presented. Gates suggests steps IRA should take to revive and redirect reading research. McCallister discusses the implications of the changing and expanding vocabulary of…

  8. Addressing Sexual Harassment

    ERIC Educational Resources Information Center

    Young, Ellie L.; Ashbaker, Betty Y.

    2008-01-01

    This article discusses ways on how to address the problem of sexual harassment in schools. Sexual harassment--simply defined as any unwanted and unwelcome sexual behavior--is a sensitive topic. Merely providing students, parents, and staff members with information about the school's sexual harassment policy is insufficient; schools must take…

  9. Site-specific chemokine expression regulates CNS inflammation and determines clinical phenotype in autoimmune encephalomyelitis1

    PubMed Central

    Stoolman, Joshua S.; Duncker, Patrick C.; Huber, Amanda K.; Segal, Benjamin M.

    2014-01-01

    The adoptive transfer of myelin-reactive T cells into wildtype (WT)2 hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoutoimmune encephalitis (EAE)3, as opposed to brainstem inflammation and ataxia, which characterize disease in IFNγRKO hosts (atypical EAE). Here we show that atypical EAE correlates with preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2 dependent recruitment of neutrophils. In contrast, conventional EAE is associated with upregulation of CCL2 in the spinal cord, and is driven by recruitment of monocytes via a partially CCR2-dependent pathway. This study illustrates how regional differences in chemokine expression within a target organ shape the spatial pattern and composition of autoimmune infiltrates, leading to disparate clinical outcomes. PMID:24928987

  10. Ezetimibe: an update on its clinical usefulness in specific patient groups

    PubMed Central

    Hammersley, Daniel; Signy, Mark

    2016-01-01

    The aim of pharmacological lipid modification is to reduce low-density lipoprotein cholesterol (LDL-C) as a means of either secondary or primary prevention of cardiovascular disease. Statins are the first-line therapy for pharmacological lipid modification. Ezetimibe is a drug which reduces LDL-C by selectively inhibiting intestinal cholesterol absorption. This provides an alternative pharmacological approach to that of statin therapy to reduce LDL-C. Ezetimibe has been shown to significantly reduce levels of LDL-C and recently, as demonstrated in the IMPROVE-IT trial, to reduce the rate of cardiovascular events in high-risk patients. Ezetimibe therefore has an important role in pharmacological lipid modification. In this paper, we examine the body of research behind ezetimibe and assess its current clinical applications in different patient subgroups. PMID:28203346

  11. [Clinical importance of organ-specific antibodies in ulcerative colitis and Crohn disease].

    PubMed

    Goischke, E M; Zilly, W

    1992-05-01

    In 479 patients with chronic inflammatory intestinal diseases and other abdominal diseases autoantibodies against intestinal goblet cells and exocrine pancreas were determined by indirect immunofluorescence. In ulcerative colitis 17% had serum antibodies against intestinal goblet cells, in Crohn's disease 26% against exocrine pancreas. Autoantibody prevalence and level of the titre were dependent on the inflammatory activity of both diseases but independent on the therapy. In Crohn's disease high level of titres of antibodies against exocrine pancreas we found in cases with multiple complications. Antibodies titres against intestinal goblet cells in ulcerative colitis and against exocrine pancreas in Crohn's disease exceeding 1:100 improved the diagnostic decision. Besides clinical states, endoscopic and histological findings a positive result of the antibody investigations had to be considered for final diagnosis.

  12. Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development

    PubMed Central

    Niki, Mamiko; Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Ohta, Ken; Inoue, Manabu; Niki, Makoto; Kaneko, Yukihiro; Morimoto, Kozo; Kurashima, Atsuyuki; Kitada, Seigo; Matsumoto, Sohkichi; Suzuki, Koichi; Hoshino, Yoshihiko

    2015-01-01

    Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies. PMID:26568961

  13. Performance-based quality specifications: the relationship between process critical control parameters, critical quality attributes, and clinical performance.

    PubMed

    Short, Steven M; Cogdill, Robert P; Drennen, James K; Anderson, Carl A

    2011-04-01

    The quality of pharmaceutical products is currently evaluated through a series of tests that do not explicitly communicate the clinical consequences of product variability. A previously published risk simulation platform was used to generate quantitative estimates of inefficacy and toxicity for 288 uniform lots of extended-release theophylline tablets displaying various levels of content uniformity and dissolution variability. These data were used to evaluate the univariate specifications utilized in the United States Pharmacopeia (USP) <711> and <905>. Simulation revealed that the specifications are too lenient for content uniformity, both in terms of inefficacy and toxicity, whereas the criteria for dissolution testing are too strict for inefficacy and inaccurate for toxicity. The USP tests also failed to pinpoint the clinical interaction between content uniformity and dissolution variability. Additionally, the simulation platform was used to define the underlying relationship between product quality attributes and clinical performance. Here, content uniformity and Weibull dissolution time constants were used as inputs to the design spaces, which were conditioned on quantitative estimates of inefficacy and toxicity. This methodology enhances the information content of the design space by omitting quality surrogates (e.g., dissolution, moisture content) that are utilized in current design space practices.

  14. Body checking in non-clinical women: experimental evidence of a specific impact on fear of uncontrollable weight gain.

    PubMed

    Bailey, Natalie; Waller, Glenn

    2017-01-20

    Body checking is used widely among clinical and non-clinical individuals. It is suggested to be a safety behavior, reducing anxiety initially but potentially enhancing eating and shape concerns in the longer term. However, there is little causal evidence of those negative effects. This experimental study tests the potential negative impact of body checking. Fifty non-clinical women took part in a study of the effects of body checking in naturalistic settings. Each checked their wrist size every 15 minutes for eight hours on one day, then did not check the next day (order randomized). The impact on eating cognitions and body dissatisfaction was measured at the end of each day, and levels of change in those characteristics were also associated with eating pathology levels. Body checking did not result in more negative general eating attitudes or body dissatisfaction, but did result in a significant increase in a specific cognition that is hypothesised to be relevant to eating pathology - the fear of uncontrollable weight gain following eating. This impact was greater among those women with more negative existing eating attitudes. These findings add to the small experimental evidence base, demonstrating negative causal links between body checking and eating pathology. The findings need to be extended to clinical groups, but support the use of existing cognitive-behavioral methods to reduce body checking behavior.

  15. A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

    PubMed Central

    Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

    2015-01-01

    Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

  16. Patient-specific assessment of left ventricular thrombogenesis risk after acute myocardial infarction: a pilot clinical study

    NASA Astrophysics Data System (ADS)

    Rossini, L.; Khan, A.; Del Alamo, J. C.; Martinez-Legazpi, P.; Pérez Del Villar, C.; Benito, Y.; Yotti, R.; Barrio, A.; Delgado-Montero, A.; Gonzalez-Mansilla, A.; Fernandez-Avilés, F.; Bermejo, J.

    2016-11-01

    Left ventricular thrombosis (LVT) is a major complication of acute myocardial infarction (AMI). In these patients, the benefits of chronic anticoagulation therapy need to be balanced with its pro-hemorrhagic effects. Blood stasis in the cardiac chambers, a risk factor for LVT, is not addressed in current clinical practice. We recently developed a method to quantitatively assess the blood residence time (RT) inside the left ventricle (LV) based on 2D color-Doppler velocimetry (echo-CDV). Using time-resolved blood velocity fields acquired non-invasively, we integrate a modified advection equation to map intraventricular stasis regions. Here, we present how this tool can be used to estimate the risk of LVT in patients with AMI. 73 patients with a first anterior-AMI were studied by echo-CDV and RT analysis within 72h from admission and at a 5-month follow-up. Patients who eventually develop LVT showed early abnormalities of intraventricular RT: the apical region with RT>2s was significantly larger, had a higher RT and a longer wall contact length. Thus, quantitative analysis of intraventricular flow based on echocardiography may provide subclinical markers of LV thrombosis risk to guide clinical decision making.

  17. An "alternating instructions" version of the Autobiographical Memory Test for assessing autobiographical memory specificity in non-clinical populations.

    PubMed

    Dritschel, Barbara; Beltsos, Stamatis; McClintock, Shawn M; Beltosis, Stamatis

    2014-01-01

    There is limited research regarding how executive processes contribute to key cognitive deficits in depression, particularly impoverished retrieval of autobiographical memory. This study tested a novel version of the Autobiographical Memory Test (AMT), the "Alternating Instructions" AMT (AMT-AI), to determine how participants could flexibly retrieve specific and categoric autobiographical memories. The AMT-AI consisted of a standard AMT (AMT-S), a categoric version of the AMT (AMT-R), and a section of alternating instructions (AI) in which the rules required the participant to alternate between retrieval of categoric and specific memories. A total of 49 university students completed the AMT-AI, and self-report measures of depressive symptomatology and ruminative thinking. Results showed that the mean proportion of specific memories recalled on the AMT-AI was significantly lower than on the AMT-S. Also, reduced memory specificity on the AMT-AI, but not the AMT-S, was significantly negatively correlated with increased scores on measures of depressive symptomatology and ruminative thinking. Collectively the data suggested that the AMT-AI, relative to the traditional AMT, may be more sensitive to memory specificity in non-clinical populations. Future research is warranted to further determine the psychometric properties and utility of the AMT-AI.

  18. Frequency-specific electric response audiometry (ERA) and its clinical application in the diagnosis of hearing defects in the dog.

    PubMed

    Schacks, S; Rohn, K; Hauschild, G

    2006-03-01

    Reference values were established for frequency-specific electric response audiometry (ERA) in dogs on the basis of the results of ERA examinations of 200 animals with normal hearing. Air-conducting acoustic tubes with foam stoppers were used in the determination of the following: the latencies of waves I, III and V; interpeak latencies (IPL) I-III, III-V and I-V; amplitudes I and V; and the amplitude difference I-V. A frequency-specific stimulus (tone pip) was used for frequency-specific examination (1 to 4 kHz) over the entire frequency range indicated. These reference values were then used for the clinical examination of 50 dogs with hearing defects. A frequency-specific ERA was conducted and the results evaluated. These findings made it possible to draw objective conclusions about the degree, type and site of the hearing defects. Frequency-specific electric response audiometry was shown to be an important diagnostic tool for the detection of partial high- and low-frequency hearing loss and for the characterisation of hearing defects of otological, otoneurological and neurological origin.

  19. Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes

    PubMed Central

    Murakoshi, Hayato; Akahoshi, Tomohiro; Koyanagi, Madoka; Chikata, Takayuki; Naruto, Takuya; Maruyama, Rie; Tamura, Yoshiko; Ishizuka, Naoki; Gatanaga, Hiroyuki; Oka, Shinichi

    2015-01-01

    ABSTRACT Identification and characterization of CD8+ T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8+ T cells have been only partially identified. In this study, we sought to identify CD8+ T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8+ T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10−11) and positively associated with CD4 count (P = 1.2 × 10−11), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8+ T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes. IMPORTANCE HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52

  20. Content Addressable Memory Project

    DTIC Science & Technology

    1990-11-01

    The Content Addressable M1-emory Project consists of the development of several experimental software systems on an AMT Distributed Array Processor...searching (database) compiler algorithms memory management other systems software) Linear C is an unlovely hybrid language which imports the CAM...memory from AMT’s operating system for the DAP; how- ever, other than this limitation, the memory management routines work exactly as their C counterparts

  1. Predicting early spelling difficulties in children with specific language impairment: a clinical perspective.

    PubMed

    Cordewener, Kim A H; Bosman, Anna M T; Verhoeven, Ludo

    2012-01-01

    This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in The Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered as precursors, as was spelling level at an earlier point in time. Spelling difficulties at the end of first grade were most accurately identified by letter knowledge at the beginning of first grade and word spelling at the middle of first grade. It is concluded that spelling development in children with SLI can be seen as an autocatalytic process in which, without intervention, poor spellers generally remain poor spellers, and good spellers remain good spellers. A focus on early spelling intervention is thus emphasized.

  2. Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains

    PubMed Central

    Kurushima, Jun; Ike, Yasuyoshi

    2016-01-01

    ABSTRACT Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis. Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis. Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA. Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. IMPORTANCE Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the

  3. Specificity of lectin-immobilized fluorescent nanospheres for colorectal tumors in a mouse model which more resembles the clinical disease

    PubMed Central

    Kitamura, Tokio; Sakuma, Shinji; Shimosato, Moe; Higashino, Haruki; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Hiwatari, Ken-ichiro; Kumagai, Hironori; Morimoto, Naoki; Koike, Seiji; Tobita, Etsuo; Hoffman, Robert M.; Gore, John C.; Pham, Wellington

    2014-01-01

    We are investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of this study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to more resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real-time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration of them from the anus. When the luminal side of the colon was washed with PBS, most of the nanospheres drained away. However, fluorescence persisted in areas where the cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor specific and bound to tumors even after vigorously washing. The nanospheres non-specifically bound to normal mucosa were easily removed through mild washing. Results indicate that the nanospheres accompanied by colonoscopy will be a clinically-valuable diagnostic tool for the early stage primary colon carcinoma. PMID:24976331

  4. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

    PubMed

    Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

    2016-06-01

    Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers.

  5. Two Years Follow up of Domain Specific Cognitive Training in Relapsing Remitting Multiple Sclerosis: A Randomized Clinical Trial

    PubMed Central

    Mattioli, Flavia; Bellomi, Fabio; Stampatori, Chiara; Provinciali, Leandro; Compagnucci, Laura; Uccelli, Antonio; Pardini, Matteo; Santuccio, Giuseppe; Fregonese, Giuditta; Pattini, Marianna; Allegri, Beatrice; Clerici, Raffaella; Lattuada, Annalisa; Montomoli, Cristina; Corso, Barbara; Gallo, Paolo; Riccardi, Alice; Ghezzi, Angelo; Roscio, Marco; Tola, Maria Rosaria; Calanca, Chiara; Baldini, Daria; Trafficante, Debora; Capra, Ruggero

    2016-01-01

    Cognitive rehabilitation in multiple sclerosis (MS) has been reported to induce neuropsychological improvements, but the persistence of these effects has been scarcely investigated over long follow ups. Here, the results of a multicenter randomized clinical trial are reported, in which the efficacy of 15 week domain specific cognitive training was evaluated at 2 years follow up in 41 patients. Included patients were randomly assigned either to domain specific cognitive rehabilitation, or to aspecific psychological intervention. Patients who still resulted to be cognitively impaired at 1 year follow up were resubmitted to the same treatment, whereas the recovered ones were not. Neuropsychological tests and functional scales were administered at 2 years follow up to all the patients. Results revealed that both at 1 and at 2 years follow up more patients in the aspecific group (18/19, 94% and 13/17, 76% respectively) than in the specific group (11/22, 50% and 5/15, 33% respectively) resulted to be cognitively impaired. Furthermore patients belonging to the specific group showed significantly less impaired tests compared with the aspecific group ones (p = 0.02) and a significant amelioration in the majority of the tests. On the contrary patients in the aspecific group did not change. The specific group subjects also perceived a subjective improvement in their cognitive performance, while the aspecific group patients did not. These results showed that short time domain specific cognitive rehabilitation is a useful treatment for patients with MS, shows very long lasting effects, compared to aspecific psychological interventions. Also subjective cognitive amelioration was found in patients submitted to domain specific treatment after 2 years. PMID:26941630

  6. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2... 20580, unless otherwise specifically directed. The Commission's Web site address is www.ftc.gov....

  7. [Specific clinical and functional features in the patients presenting with neurologic manifestations of deforming dorsopathies and concomitant osteoarthrosis].

    PubMed

    Miriutova, N F; Zaĭtsev, A A; Popova, A V

    2012-01-01

    The present study has revealed some specific clinical and functional features in the patients presenting with neurologic manifestations of deforming dorsopathies and concomitant osteoarthrosis. The negative influence of the latter condition on the pain intensity, microcirculation, and duration of the exacerbation of neurologic syndrome has been demonstrated based on the analysis of correlational relationships between the severity of referred projectional nerve root pain and articular pain syndrome. Special emphasis is laid on the interrelation between the duration of pain syndrome and characteristics of microcirculation.

  8. Antibodies specific for nucleic acids and applications in genomic detection and clinical diagnostics.

    PubMed

    Hu, Zonglin; Leppla, Stephen H; Li, Baoguang; Elkins, Christopher A

    2014-09-01

    Detection of nucleic acids using antibodies is uncommon. This is in part because nucleic acids are poor immunogens and it is difficult to elicit antibodies having high affinity to each type of nucleic acid while lacking cross-reactivity to others. We describe the origins and applications of a variety of anti-nucleic acid antibodies, including ones reacting with modified nucleosides and nucleotides, single-stranded DNA, double-stranded DNA, RNA, DNA:RNA hybrids, locked-nucleic acids or peptide nucleic acid:nucleic acid hybrids. Carefully selected antibodies can be excellent reagents for detecting bacteria, viruses, small RNAs, microRNAs, R-loops, cancer cells, stem cells, apoptotic cells and so on. The detection may be sensitive, simple, rapid, specific, reproducible, quantitative and cost-effective. Current microarray and diagnostic methods that depend on cDNA or cRNA can be replaced by using antibody detection of nucleic acids. Therefore, development should be encouraged to explore new utilities and create a robust arsenal of new anti-nucleic acid antibodies.

  9. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    PubMed

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-09-07

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages.

  10. Female-specific pruritus from childhood to postmenopause: clinical features, hormonal factors, and treatment considerations.

    PubMed

    Rimoin, Lauren P; Kwatra, Shawn G; Yosipovitch, Gil

    2013-01-01

    There have been considerable advances in our understanding of the pathophysiology of pruritus in recent years. The purpose of this review was to highlight itch entities in women, and in particular pruritic vulvar dermatoses that women experience among different age groups. Unique temporal shifts may contribute to the etiology of many of these conditions. These changes lead to cyclical changes in the skin's basic composition. Specifically, estrogen receptors have been detected on keratinocytes that respond to rising and falling levels of estrogen. These receptors lead to changes in skin hydration, collagen content, and in the concentration of glycosaminoglycans that form the skin barrier. In addition, hormonal pH changes associated with the menstrual cycle may be an important factor in the aggravation of itch as increasing pH is known to activate the proteinase-activated receptor-2, a well-known itch mediator. Common pruritic conditions in women that will be discussed include atopic and irritant dermatitis, psoriasis, lichen sclerosus, infectious vulvovaginitis, vulvovaginal candidiasis, atrophic vulvovaginitis, squamous cell carcinoma, lichen simplex chronicus, and neuropathic itch. We also examine pruritic conditions associated with pregnancy including pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy and atopic eruption of pregnancy. Finally, acceptable and contraindicated antipruritic agents in pregnancy are examined.

  11. Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician.

    PubMed

    Levy, H B

    1976-05-01

    Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the "soft signs" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life.

  12. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport

    PubMed Central

    Fernández-Suárez, María E.; Escolà-Gil, Joan C.; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A.; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [3H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [3H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  13. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

    PubMed Central

    Furman, David; Chang, Junlei; Lartigue, Lydia; Bolen, Christopher R; Haddad, François; Gaudilliere, Brice; Ganio, Edward A; Fragiadakis, Gabriela K; Spitzer, Matthew H; Douchet, Isabelle; Daburon, Sophie; Moreau, Jean-François; Nolan, Garry P; Blanco, Patrick; Déchanet-Merville, Julie; Dekker, Cornelia L; Jojic, Vladimir; Kuo, Calvin J; Davis, Mark M; Faustin, Benjamin

    2017-01-01

    Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N4-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions. PMID:28092664

  14. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    PubMed

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  15. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states.

    PubMed

    Furman, David; Chang, Junlei; Lartigue, Lydia; Bolen, Christopher R; Haddad, François; Gaudilliere, Brice; Ganio, Edward A; Fragiadakis, Gabriela K; Spitzer, Matthew H; Douchet, Isabelle; Daburon, Sophie; Moreau, Jean-François; Nolan, Garry P; Blanco, Patrick; Déchanet-Merville, Julie; Dekker, Cornelia L; Jojic, Vladimir; Kuo, Calvin J; Davis, Mark M; Faustin, Benjamin

    2017-02-01

    Low-grade, chronic inflammation has been associated with many diseases of aging, but the mechanisms responsible for producing this inflammation remain unclear. Inflammasomes can drive chronic inflammation in the context of an infectious disease or cellular stress, and they trigger the maturation of interleukin-1β (IL-1β). Here we find that the expression of specific inflammasome gene modules stratifies older individuals into two extremes: those with constitutive expression of IL-1β, nucleotide metabolism dysfunction, elevated oxidative stress, high rates of hypertension and arterial stiffness; and those without constitutive expression of IL-1β, who lack these characteristics. Adenine and N(4)-acetylcytidine, nucleotide-derived metabolites that are detectable in the blood of the former group, prime and activate the NLRC4 inflammasome, induce the production of IL-1β, activate platelets and neutrophils and elevate blood pressure in mice. In individuals over 85 years of age, the elevated expression of inflammasome gene modules was associated with all-cause mortality. Thus, targeting inflammasome components may ameliorate chronic inflammation and various other age-associated conditions.

  16. Patient specific modeling of the HPA axis related to clinical diagnosis of depression.

    PubMed

    Bangsgaard, Elisabeth O; Ottesen, Johnny T

    2016-11-02

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment.

  17. Development of Specific Sequence-Characterized Amplified Region Markers for Detecting Histoplasma capsulatum in Clinical and Environmental Samples

    PubMed Central

    Frías De León, María Guadalupe; Arenas López, Gabina; Taylor, Maria Lucia; Acosta Altamirano, Gustavo

    2012-01-01

    Sequence-characterized amplified region (SCAR) markers, generated by randomly amplified polymorphic DNA (RAPD)-PCR, were developed to detect Histoplasma capsulatum selectively in clinical and environmental samples. A 1,200-bp RAPD-PCR-specific band produced with the 1281-1283 primers was cloned, sequenced, and used to design two SCAR markers, 1281-1283220 and 1281-1283230. The specificity of these markers was confirmed by Southern hybridization. To evaluate the relevance of the SCAR markers for the diagnosis of histoplasmosis, another molecular marker (M antigen probe) was used for comparison. To validate 1281-1283220 and 1281-1283230 as new tools for the identification of H. capsulatum, the specificity and sensitivity of these markers were assessed for the detection of the pathogen in 36 clinical (17 humans, as well as 9 experimentally and 10 naturally infected nonhuman mammals) and 20 environmental (10 contaminated soil and 10 guano) samples. Although the two SCAR markers and the M antigen probe identified H. capsulatum isolates from different geographic origins in America, the 1281-1283220 SCAR marker was the most specific and detected the pathogen in all samples tested. In contrast, the 1281-1283230 SCAR marker and the M antigen probe also amplified DNA from Aspergillus niger and Cryptococcus neoformans, respectively. Both SCAR markers detected as little as 0.001 ng of H. capsulatum DNA, while the M antigen probe detected 0.5 ng of fungal DNA. The SCAR markers revealed the fungal presence better than the M antigen probe in contaminated soil and guano samples. Based on our results, the 1281-1283220 marker can be used to detect and identify H. capsulatum in samples from different sources. PMID:22189121

  18. [Clinical significance of ID4 methylation detection by quantitative methylation-specific PCR in acute leukemia].

    PubMed

    Liu, Yang; Zhong, Wen-Wen; Kang, Hui-Yuan; Wang, Li-Li; Lu, Xue-Chun; Yu, Li; Zhu, Hong-Li

    2014-06-01

    The advances of treatment improved the prognosis of the patients with acute leukemia (AL) in the last decade, but the lack of general biomarker for predicting relapse in AL, which is one of the most important factors influencing the survival and prognosis. DNA methylation of ID4 gene promoter occurred frequently in patients with AL and was found to be highly related to the tumor progression. Based on the previous work of the setup of methylation-specific quantitative PCR system for ID4 gene, this study was designed to investigate the relation between the quantitative indicator of methylation density, percentage of methylation reference(PMR) value, and different disease status of AL. PMR of ID4 was detected by MS-PCR in bone marrow (BM) samples of 17 healthy persons and 54 AL patients in the status of newly diagnosis, complete remission and disease relapse. The results showed that at different disease status, PMR value in newly diagnosed group was significantly lower than that in complete remission group (P = 0.031). Among serial samples, PMR value remained very low at the status of patients with continuous complete remission (<1.5‰), and increased along with the accumulation of tumor cells at relapse. In 1 relapse case, the abnormal rise of PMR value occurred prior to morphological relapse. PMR value seemed to be related to body tumor cell load. It is concluded that the quantitative indicator of methylation density and PMR value may reflect the change of tumor cell load in acute leukemia patients. Dynamic monitoring of PMR maybe predict leukemia relapse.

  19. Molecular and clinical dissection of CD24 antibody specificity by a comprehensive comparative analysis.

    PubMed

    Kristiansen, Glen; Machado, Eda; Bretz, Niko; Rupp, Christian; Winzer, Klaus-Jürgen; König, Anne-Kathleen; Moldenhauer, Gerhard; Marmé, Frederik; Costa, Julia; Altevogt, Peter

    2010-07-01

    CD24 is a small, highly glycosylated cell surface protein that is linked to the membrane through a glycosyl-phosphatidylinositol anchor. It is overexpressed in many human carcinomas and its expression is linked to bad prognosis. Lately, lack or low expression of CD24 was used to identify tumor stem cells resulting in conflicting data on the usefulness of this marker. In many immunohistochemical studies, the mAb SN3b was used but the epitope and specificity of this antibody have never been thoroughly investigated. In other studies based mainly on cytofluorographic analysis, the mAb ML-5 was applied. In this study, we compared the epitope of mAb SN3b to the CD24 mAbs SWA-11 and ML-5 that both bind to the core protein of CD24. Using tissue microarrays and affinity-purified CD24 glycoforms, we observed only a partial overlap of SN3b and SWA11 reactivity. The mAb SN3b recognizes sialic acid most likely on O-linked glycans that can occur independently of the CD24 protein backbone. The SN3b epitope was not related to common sialylated cancer-associated glycan structures. Both SN3b epitope positive or negative CD24 glycoforms supported the binding of P-selectin and Siglec-5. In breast cancer, the SN3b reactivity was associated with bad prognosis, whereas SWA11 was not. In renal cell cancer, the SN3b epitope was completely absent but SWA11 reactivity was a prognostic factor. Our results shed new light on the tumorbiological role of CD24 and resolve discrepancies in the literature related to the use of different CD24 mAbs.

  20. Gender-Specific Molecular and Clinical Features underlie Malignant Pleural Mesothelioma

    PubMed Central

    Rienzo, Assunta De; Archer, Michael A.; Yeap, Beow Y.; Dao, Nhien; Sciaranghella, Daniele; Sideris, Antonios C.; Zheng, Yifan; Holman, Alexander G.; Wang, Yaoyu E.; Dal Cin, Paola S.; Fletcher, Jonathan A.; Rubio, Renee; Croft, Larry; Quackenbush, John; Sugarbaker, Peter E.; Munir, Kiara J.; Battilana, Jesse R.; Gustafson, Corinne E.; Chirieac, Lucian R.; Ching, Soo Meng; Wong, James; Tay, Liang Chung; Rudd, Stephen; Hercus, Robert; Sugarbaker, David J.; Richards, William G.; Bueno, Raphael

    2015-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (p<0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that non-epitheliod histology (p=0.037), whereas CDKN2A deletions occurred more frequently in non-epithelioid subtypes among men (p=0.021) and were correlated with shorter overall survival for the entire cohort (p=0.002) and for men (p=0.012). Furthermore, women were more likely to harbor TP53 mutations (p=0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in non-epithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. PMID:26554828

  1. Bioreactors Addressing Diabetes Mellitus

    PubMed Central

    Minteer, Danielle M.; Gerlach, Jorg C.

    2014-01-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies. PMID:25160666

  2. Bioreactors addressing diabetes mellitus.

    PubMed

    Minteer, Danielle M; Gerlach, Jorg C; Marra, Kacey G

    2014-11-01

    The concept of bioreactors in biochemical engineering is a well-established process; however, the idea of applying bioreactor technology to biomedical and tissue engineering issues is relatively novel and has been rapidly accepted as a culture model. Tissue engineers have developed and adapted various types of bioreactors in which to culture many different cell types and therapies addressing several diseases, including diabetes mellitus types 1 and 2. With a rising world of bioreactor development and an ever increasing diagnosis rate of diabetes, this review aims to highlight bioreactor history and emerging bioreactor technologies used for diabetes-related cell culture and therapies.

  3. Content addressable memory project

    NASA Technical Reports Server (NTRS)

    Hall, J. Storrs; Levy, Saul; Smith, Donald E.; Miyake, Keith M.

    1992-01-01

    A parameterized version of the tree processor was designed and tested (by simulation). The leaf processor design is 90 percent complete. We expect to complete and test a combination of tree and leaf cell designs in the next period. Work is proceeding on algorithms for the computer aided manufacturing (CAM), and once the design is complete we will begin simulating algorithms for large problems. The following topics are covered: (1) the practical implementation of content addressable memory; (2) design of a LEAF cell for the Rutgers CAM architecture; (3) a circuit design tool user's manual; and (4) design and analysis of efficient hierarchical interconnection networks.

  4. Prevalence and predictors of infertility-specific stress in women diagnosed with primary infertility: A clinic-based study

    PubMed Central

    Patel, Ansha; Sharma, P. S. V. N.; Narayan, Pratapkumar; Binu, V. S.; Dinesh, N.; Pai, Praveena Joglekar

    2016-01-01

    BACKGROUND: According to the existing literature on infertility, stress appears to be inevitably associated with infertility diagnosis and treatment in sub-fertile individuals. The epidemiological data on the prevalence and predictors of infertility-specific stress in cultural specific scenario are scarce. The objective of the present study was to estimate the prevalence of infertility-specific stress and identify predictors of infertility-specific stress in women diagnosed with primary infertility. MATERIALS AND METHODS: This cross-sectional study was conducted on 300 infertile married women, diagnosed with primary infertility. The tools used for the assessment were “semi-structured questionnaire” compiled by the authors, “ICD-10 Classification of Mental and Behavioral Disorders (Clinical Descriptions and Diagnostic Guidelines),” and “Psychological Evaluation Test for infertility.” STATISTICAL ANALYSIS: Data were analyzed using SPSS (version 15). Chi-square test was used for univariate analysis followed by multiple logistic regressions between stress and the predictor variables. RESULTS AND DISCUSSION: The prevalence of stress among women was 80%. Univariate analysis revealed that predictors of stress were years of marital life, duration of infertility, infertility type, history of gynecological surgery, cycles of ovulation induction with timed intercourse and intra-uterine inseminations, present and past psychiatric morbidity, coping difficulties, gynecological diagnosis, and severity of premenstrual dysphoria. Multivariate analysis showed leading associations of stress with infertility type and coping difficulties. PMID:27110075

  5. Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

    PubMed

    Kumaresan, Pappanaicken; Figliola, Mathew; Moyes, Judy S; Huls, M Helen; Tewari, Priti; Shpall, Elizabeth J; Champlin, Richard; Cooper, Laurence J N

    2015-10-05

    The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced

  6. Addressing Environmental Health Inequalities

    PubMed Central

    Gouveia, Nelson

    2016-01-01

    Environmental health inequalities refer to health hazards disproportionately or unfairly distributed among the most vulnerable social groups, which are generally the most discriminated, poor populations and minorities affected by environmental risks. Although it has been known for a long time that health and disease are socially determined, only recently has this idea been incorporated into the conceptual and practical framework for the formulation of policies and strategies regarding health. In this Special Issue of the International Journal of Environmental Research and Public Health (IJERPH), “Addressing Environmental Health Inequalities—Proceedings from the ISEE Conference 2015”, we incorporate nine papers that were presented at the 27th Conference of the International Society for Environmental Epidemiology (ISEE), held in Sao Paulo, Brazil, in 2015. This small collection of articles provides a brief overview of the different aspects of this topic. Addressing environmental health inequalities is important for the transformation of our reality and for changing the actual development model towards more just, democratic, and sustainable societies driven by another form of relationship between nature, economy, science, and politics. PMID:27618906

  7. Identification of ssDNA aptamers specific to clinical isolates of Streptococcus mutans strains with different cariogenicity.

    PubMed

    Cui, Wei; Liu, Jiaojiao; Su, Donghua; Hu, Danyang; Hou, Shuai; Hu, Tongnan; Yang, Jiyong; Luo, Yanping; Xi, Qing; Chu, Bingfeng; Wang, Chenglong

    2016-06-01

    Streptococcus mutans, a Gram-positive facultative anaerobic bacterium, is considered to be a major etiological factor for dental caries. In this study, plaques from dental enamel surfaces of caries-active and caries-free individuals were obtained and cultivated for S. mutans isolation. Morphology examination, biochemical characterization, and polymerase chain reaction were performed to identify S. mutans The cariogenicity of S. mutans strains isolated from clinical specimens was evaluated by testing the acidogenicity, aciduricity, extracellular polysaccharide production, and adhesion ability of the bacteria. Finally, subtractive SELEX (systematic evolution of ligands by exponential enrichment) technology targeting whole intact cells was used to screen for ssDNA aptamers specific to the strains with high cariogenicity. After nine rounds of subtractive SELEX, sufficient pool enrichment was achieved as shown by radioactive isotope analysis. The enriched pool was cloned and sequenced randomly, followed by MEME online and RNA structure software analysis of the sequences. Results from the flow cytometry indicated that aptamers H1, H16, H4, L1, L10, and H19 could discriminate highly cariogenic S. mutans strains from poorly cariogenic strains. Among these, Aptamer H19 had the strongest binding capacity with cariogenic S. mutans strains with a dissociation constant of 69.45 ± 38.53 nM. In conclusion, ssDNA aptamers specific to highly cariogenic clinical S. mutans strains were successfully obtained. These ssDNA aptamers might be used for the early diagnosis and treatment of dental caries.

  8. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS

    PubMed Central

    Kong, Byung Soo; Lee, Jung-Eun; Kim, Kyoung Heon; Lee, Do Yup; Kim, Ho Jin

    2016-01-01

    Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs. PMID:27855220

  9. Towards personalised management of atherosclerosis via computational models in vascular clinics: technology based on patient-specific simulation approach.

    PubMed

    Díaz-Zuccarini, Vanessa; Di Tomaso, Giulia; Agu, Obiekezie; Pichardo-Almarza, Cesar

    2014-01-01

    The development of a new technology based on patient-specific modelling for personalised healthcare in the case of atherosclerosis is presented. Atherosclerosis is the main cause of death in the world and it has become a burden on clinical services as it manifests itself in many diverse forms, such as coronary artery disease, cerebrovascular disease/stroke and peripheral arterial disease. It is also a multifactorial, chronic and systemic process that lasts for a lifetime, putting enormous financial and clinical pressure on national health systems. In this Letter, the postulate is that the development of new technologies for healthcare using computer simulations can, in the future, be developed as in-silico management and support systems. These new technologies will be based on predictive models (including the integration of observations, theories and predictions across a range of temporal and spatial scales, scientific disciplines, key risk factors and anatomical sub-systems) combined with digital patient data and visualisation tools. Although the problem is extremely complex, a simulation workflow and an exemplar application of this type of technology for clinical use is presented, which is currently being developed by a multidisciplinary team following the requirements and constraints of the Vascular Service Unit at the University College Hospital, London.

  10. Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria.

    PubMed

    Pfaller, Michael A; Andes, David; Arendrup, Maiken C; Diekema, Daniel J; Espinel-Ingroff, Ana; Alexander, Barbara D; Brown, Steven D; Chaturvedi, Vishnu; Fowler, Cynthia L; Ghannoum, Mahmoud A; Johnson, Elizabeth M; Knapp, Cynthia C; Motyl, Mary R; Ostrosky-Zeichner, Luis; Walsh, Thomas J

    2011-07-01

    We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs. Adjusted 24-h CBPs for voriconazole and C. albicans, C. tropicalis, and C. parapsilosis (susceptible, ≤ 0.125 μg/mL; intermediate, 0.25-0.5 μg/mL; resistant, ≥ 1 μg/mL) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs. In the absence of CBPs for voriconazole and C. glabrata (and less common species), we recommend that their respective ECVs be used to detect the emergence of non-WT strains.

  11. [Bioethics in clinical practice].

    PubMed

    Sánchez-Gonzaléz, Miguel; Herreros, Benjamín

    2015-01-01

    Bioethics has grown exponentially in recent decades. Its most important schools include principlism, casuistry, virtue ethics and the ethics of care. These schools are not exclusive. Within bioethics, clinical ethics addresses the inherent clinical practice ethical problems, problems which are many and very varied. Bioethics training is essential for clinicians to address these bioethics' problems. But even the professionals are trained, there are problems that cannot be solved individually and require advisory groups in clinical ethics: clinical ethics committees. These committees are also responsible for education in bioethics in health institutions. Clinical bioethics is a practical discipline, oriented to address specific problems, so its development is necessary to improve the decision making in such complex problems, inevitable problems in healthcare.

  12. Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model

    PubMed Central

    Faggiano, Elena; Boffano, Carlo; Acerbi, Francesco; Ciarletta, Pasquale

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient’s prognosis. PMID:26186462

  13. [Keynote address: Climate change

    SciTech Connect

    Forrister, D.

    1994-12-31

    Broadly speaking, the climate issue is moving from talk to action both in the United States and internationally. While few nations have adopted strict controls or stiff new taxes, a number of them are developing action plans that are making clear their intention to ramp up activity between now and the year 2000... and beyond. There are sensible, economically efficient strategies to be undertaken in the near term that offer the possibility, in many countries, to avoid more draconian measures. These strategies are by-and-large the same measures that the National Academy of Sciences recommended in a 1991 report called, Policy Implications of Greenhouse Warming. The author thinks the Academy`s most important policy contribution was how it recommended the nations act in the face of uncertain science and high risks--that cost effective measures are adopted as cheap insurance... just as nations insure against other high risk, low certainty possibilities, like catastrophic health insurance, auto insurance, and fire insurance. This insurance theme is still right. First, the author addresses how the international climate change negotiations are beginning to produce insurance measures. Next, the author will discuss some of the key issues to watch in those negotiations that relate to longer-term insurance. And finally, the author will report on progress in the United States on the climate insurance plan--The President`s Climate Action Plan.

  14. Development of Peptide-Based Lineage-Specific Serology for Chronic Chagas Disease: Geographical and Clinical Distribution of Epitope Recognition

    PubMed Central

    Bhattacharyya, Tapan; Falconar, Andrew K.; Luquetti, Alejandro O.; Costales, Jaime A.; Grijalva, Mario J.; Lewis, Michael D.; Messenger, Louisa A.; Tran, Trang T.; Ramirez, Juan-David; Guhl, Felipe; Carrasco, Hernan J.; Diosque, Patricio; Garcia, Lineth; Litvinov, Sergey V.; Miles, Michael A.

    2014-01-01

    Background Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI–TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues. Methodology/Principal Findings We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology. Conclusions

  15. Naming speed as a clinical marker in predicting basic calculation skills in children with specific language impairment.

    PubMed

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2012-01-01

    The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on cognitive, linguistic and basic calculation skills. The results showed that phonological awareness, grammatical ability, general intelligence and working memory accounted for the variation in the basic calculation skills of both groups. However, an additional effect of naming speed on both addition and subtraction was found for the group of children with SLI, suggesting that naming speed may act as a clinical marker in identifying those children who are likely to develop problems in basic calculation skills.

  16. Interactive cervical motion kinematics: sensitivity, specificity and clinically significant values for identifying kinematic impairments in patients with chronic neck pain.

    PubMed

    Sarig Bahat, Hilla; Chen, Xiaoqi; Reznik, David; Kodesh, Einat; Treleaven, Julia

    2015-04-01

    Chronic neck pain has been consistently shown to be associated with impaired kinematic control including reduced range, velocity and smoothness of cervical motion, that seem relevant to daily function as in quick neck motion in response to surrounding stimuli. The objectives of this study were: to compare interactive cervical kinematics in patients with neck pain and controls; to explore the new measures of cervical motion accuracy; and to find the sensitivity, specificity, and optimal cutoff values for defining impaired kinematics in those with neck pain. In this cross-section study, 33 patients with chronic neck pain and 22 asymptomatic controls were assessed for their cervical kinematic control using interactive virtual reality hardware and customized software utilizing a head mounted display with built-in head tracking. Outcome measures included peak and mean velocity, smoothness (represented by number of velocity peaks (NVP)), symmetry (represented by time to peak velocity percentage (TTPP)), and accuracy of cervical motion. Results demonstrated significant and strong effect-size differences in peak and mean velocities, NVP and TTPP in all directions excluding TTPP in left rotation, and good effect-size group differences in 5/8 accuracy measures. Regression results emphasized the high clinical value of neck motion velocity, with very high sensitivity and specificity (85%-100%), followed by motion smoothness, symmetry and accuracy. These finding suggest cervical kinematics should be evaluated clinically, and screened by the provided cut off values for identification of relevant impairments in those with neck pain. Such identification of presence or absence of kinematic impairments may direct treatment strategies and additional evaluation when needed.

  17. Anti-Malassezia-Specific IgE Antibodies Production in Japanese Patients with Head and Neck Atopic Dermatitis: Relationship between the Level of Specific IgE Antibody and the Colonization Frequency of Cutaneous Malassezia Species and Clinical Severity

    PubMed Central

    Zhang, Enshi; Tanaka, Takafumi; Tajima, Mami; Tsuboi, Ryoji; Kato, Hiroshi; Nishikawa, Akemi; Sugita, Takashi

    2011-01-01

    Atopic dermatitis of the head and neck (HNAD) is recognized as a separate condition. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate atopic dermatitis (AD), especially HNAD. In the present study, we investigated the relationships between the levels of specific IgE antibodies, colonization frequency of eight predominant Malassezia species, and clinical severity in 61 patients with HNAD (26 mild, 24 moderate, and 11 severe cases). As clinical severity increased, the levels of specific IgE antibodies against eight Malassezia species also increased. Species diversity of the Malassezia microbiota in scale samples from patients was analyzed by nested PCR using species-specific primers. The clinical severity of HNAD was correlated with the total level of specific IgE antibodies against Malassezia species and the number of Malassezia species detected. PMID:22253636

  18. Pneumocystis jiroveci in Portuguese immunocompromised patients: association of specific ITS genotypes with treatment failure, bad clinical outcome and childhood.

    PubMed

    Matos, Olga; Lee, Chao-Hung; Jin, Shaoling; Li, Baozheng; Costa, Marina C; Gonçalves, Luzia; Antunes, Francisco

    2003-11-01

    We analyzed the genetic variation among isolates of Pneumocystis jiroveci from Portuguese immunocompromised patients with PCP at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon and at the dihydropteroate synthase (DHPS) gene. Pulmonary secretions from 42 patients with PCP corresponding to 43 episodes were studied. Demographic, immunological, and clinical data were obtained from all patients. By combining the two regions ITS1 and ITS2, we found 17 different ITS types of P. jiroveci, two of them were new types (Pb and Pe). The four most prevalent ITS types were Eg (23.3%), Eb and Ne (11.6% each), and Bi (9.3%). A single type was detected in 95.3% of the samples and 4.7% had mixed infections with three different ITS types. DHPS mutants were present in 17 (46%), and the wildtype was present in 20 (54%) of 37 isolates. No association was found between ITS and DHPS types and between DHPS types and therapy or response to anti-PCP treatment. Type Ne presented an association with negative response to anti-PCP treatment (P<0.001) and with death before 120 days after PCP diagnosis (P=0.025). Type Eb was significantly more common in children than in adults (P=0.001). Our data suggest an association of specific ITS genotypes with treatment failure, bad clinical outcome and childhood.

  19. Evaluation of 3 analyte-specific reagents for detection of Bordetella pertussis and Bordetella parapertussis in clinical specimens.

    PubMed

    Hassan, Ferdaus; Hays, Lindsay; Bell, Jeremiah; Selvarangan, Rangaraj

    2014-11-01

    The performance of 3 analyte-specific reagents (ASRs), Elitech Biosciences, EraGen Biosciences, and Focus Diagnostic, was evaluated for detection of Bordetella pertussis (BP) and Bordetella parapertussis (BPP) in nasopharyngeal swab specimens. A total of 104 frozen, leftover clinical specimens obtained from pediatric patients during 2011-2012 were included in this study. Performance was compared to the Bordetella real-time polymerase chain reaction (PCR) laboratory-developed test (LDT). The positive percent agreement for detection of BP by Elitech was 96% (95% confidence interval [CI]: 85.14-99.30); EraGen and Focus was 98% (95% CI: 87.99-99.89) in comparison to LDT PCR assay. The negative percent agreement of Elitech, EraGen, and Focus in comparison to LDT was 96% (95% CI: 85.14-99.30), 92% (95% CI: 79.89-97.41), and 96% (95% CI: 85.14-99.30), respectively. Limit of detection (LOD) for BP was 0.1 CFU/reaction by both Focus and EraGen and 1.0 CFU/reaction by Elitech. However, LOD for BPP was lower by EraGen (0.1 CFU/reaction) compared to Focus (1.0 CFU/reaction) and Elitech (1.0 CFU/reaction). These results demonstrate that all 3 ASRs tested are comparable and reliable for routine clinical diagnosis of pertussis and parapertussis.

  20. Microwave & Magnetic (M2) Proteomics Reveals CNS-Specific Protein Expression Waves that Precede Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Raphael, Itay; Mahesula, Swetha; Purkar, Anjali; Black, David; Catala, Alexis; Gelfond, Jonathon A. L.; Forsthuber, Thomas G.; Haskins, William E.

    2014-09-01

    Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave & magnetic (M2) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M2 proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M2 proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M2 proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.

  1. "Not Just Right Experiences" are specific to obsessive-compulsive disorder: further evidence from Italian clinical samples.

    PubMed

    Sica, Claudio; Bottesi, Gioia; Orsucci, Antonella; Pieraccioli, Caterina; Sighinolfi, Cecilia; Ghisi, Marta

    2015-04-01

    Not Just Right Experiences (NJREs) are considered to be a perceptually tinged phenomenon mainly related to obsessive-compulsive disorder (OCD). The evidence of an association between NJREs and OCD or OC symptoms have been accumulating in the last few years, whereas there is a paucity of studies about the role of this construct in other clinical conditions considered part of the "OCD spectrum". In the current study, the NJRE-Q-R Severity scale (a well-validated measure of NJREs) was administered to 41 patients with OCD, 53 with hair-pulling disorder (HPD), 38 with gambling disorder (GD) and 43 with eating disorders (ED) along with measures of OC symptoms and general distress. In each group, NJREs were consistently associated with OC symptoms; moreover, the pattern of associations appeared coherent with the main clinical features of each disorder. The OCD group reported higher levels of NJREs severity than GD and ED, whereas there were no differences between the OCD and HPD groups. However, HPD patients did not have higher scores of NJREs severity than GD and ED counterparts. NJREs appear to be specific to OCD, but further study is needed to establish the role of this construct in OCD-related disorders.

  2. Development of a Pediatric-Specific Clinical Probability Tool for Diagnosis of Venous Thromboembolism: A Feasibility Study

    PubMed Central

    Kerlin, Bryce A.; Stephens, Julie A.; Hogan, Mark J.; Smoyer, William E.; O'Brien, Sarah H.

    2014-01-01

    Background Pediatric venous thromboembolism (VTE) is an increasingly common, difficult to diagnose problem. Clinical probability tools (CPT) for adults estimate VTE likelihood, but are not available for children. We hypothesized that a pediatric-specific CPT is feasible. Methods Radiology reports were utilized to identify children imaged for suspected VTE. Relevant signs, symptoms, and co-morbidity variables, identified from published literature, were extracted from corresponding medical records. Variables associated with pediatric VTE were incorporated into a multivariate logistic regression to create a pilot CPT which was confirmed on a separate cohort. Results 389 subjects meeting inclusion criteria were identified: 91 with VTE and 298 without. Univariate analysis revealed male gender (OR 2.96; p<0.001), asymmetric extremity (OR 1.76; p=0.033), central venous catheter utilization and/or dysfunction (OR 2.51; p<0.001), and cancer (OR 2.35; p=0.014) as VTE predictive variables. Documentation of an alternate diagnosis was inversely related to VTE (OR 0.42; p=0.004). Receiver operating characteristic analysis of the derived CPT demonstrated reasonable ability to discriminate VTE probability in the training cohort (AUC 0.73; p<0.001) and moderate discrimination in a separate validation cohort of 149 children (AUC 0.64; p=0.011). Conclusion A pediatric-specific VTE CPT is feasible, would facilitate early diagnosis, and could lead to improved outcomes. PMID:25518012

  3. An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

    PubMed Central

    Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

    2014-01-01

    Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

  4. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players

    PubMed Central

    Moura, Rita C.; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician’s dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals. PMID:28321203

  5. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players.

    PubMed

    Moura, Rita C; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician's dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals.

  6. New frontiers in prostate cancer imaging: clinical utility of prostate-specific membrane antigen positron emission tomography.

    PubMed

    Afaq, Asim; Batura, Deepak; Bomanji, Jamshed

    2017-02-14

    Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a relatively new method of imaging prostate cancer that increases diagnostic accuracy in detecting and guiding management in various stages of the disease pathway. Gallium-68-labelled PSMA PET has increased the sensitivity of detection of disease recurrence at low PSA levels, thus allowing an optimal window for salvage treatment. Apart from its use in disease recurrence, PSMA PET has the potential for increasing sensitivity and specificity for primary tumour localisation and in detecting lymph node disease, leading to a more accurate initial staging of the condition. In advanced disease, the use of PSMA PET may be able to assess response to treatment and also guide treatment with radionuclide therapy. Newer ligands under development might provide avenues for theranostic or personalised therapy applications with early data showing high PSA response rates. The rate of translation of PSMA PET into clinical practice has been remarkable. The use of this modality is likely to increase with future efforts to modify the radiotracer including (18)F labelling to improve availability.

  7. Clinical Evaluation of Specific Oral Manifestations in Pediatric Patients with Ascertained versus Potential Coeliac Disease: A Cross-Sectional Study

    PubMed Central

    Matacena, Giada; Costa, Stefano; Magazzù, Giuseppe

    2014-01-01

    Patients involved on coeliac disease (CD) have atypical symptoms and often remain undiagnosed. Specific oral manifestations are effective risk indicators of CD and for this reason an early diagnosis with a consequent better prognosis can be performed by the dentist. There are not researches analysing the frequency of these oral manifestations in potential coeliac patients. The aim of this study is to investigate the oral hard and soft tissue lesions in potential and ascertained coeliac children in comparison with healthy controls. 50 ascertained children, 21 potential coeliac patients, and 54 controls were recruited and the oral examination was performed. The overall oral lesions were more frequently present in CD patients than in controls. The prevalence of oral soft tissue lesions was 62% in ascertained coeliac, 76.2% in potential coeliac patients, and 12.96% in controls (P < 0.05). Clinical dental delayed eruption was observed in 38% of the ascertained coeliac and 42.5% of the potential coeliac versus 11.11% of the controls (P < 0.05). The prevalence of specific enamel defects (SED) was 48% in ascertained coeliac and 19% in potential coeliac versus 0% in controls (P < 0.05; OR = 3.923). The SED seem to be genetically related to the histological damage and villous atrophy. PMID:25197270

  8. Addressing viral resistance through vaccines

    PubMed Central

    Laughlin, Catherine; Schleif, Amanda; Heilman, Carole A

    2015-01-01

    Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider approaches to address this growing issue. While vaccination is a logical strategy, and has been shown to be successful many times over, next generation viral vaccines with a specific goal of curbing antiviral resistance will need to clear several hurdles including vaccine design, evaluation and implementation. This article suggests that a new model of vaccination may need to be considered: rather than focusing on public health, this model would primarily target sectors of the population who are at high risk for complications from certain infections. PMID:26604979

  9. Increasing hope by addressing clients' outcome expectations.

    PubMed

    Swift, Joshua K; Derthick, Annie O

    2013-09-01

    Addressing clients' outcome expectations is an important clinical process that can lead to a strong therapeutic alliance, more positive treatment outcomes, and decreased rates of premature termination from psychotherapy. Five interventions designed to foster appropriate outcome expectations are discussed, including presenting a convincing treatment rationale, increasing clients' faith in their therapists, expressing faith in clients, providing outcome education, and comparing progress with expectations. Clinical examples and research support are provided for each.

  10. Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases

    PubMed Central

    Elnady, Basant M.; Kamal, Naglaa M.; Shaker, Raneyah H.M.; Soliman, Amal F.; Hasan, Waleed A.; Alghamdi, Hamed A.; Algethami, Mohammed M.; Jajah, Mohamed Bilal

    2016-01-01

    Abstract Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown. We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future. This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis. Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001). ATD is more associated with rheumatic

  11. CT-guided Bipolar and Multipolar Radiofrequency Ablation (RF Ablation) of Renal Cell Carcinoma: Specific Technical Aspects and Clinical Results

    SciTech Connect

    Sommer, C. M.; Lemm, G.; Hohenstein, E.; Bellemann, N.; Stampfl, U.; Goezen, A. S.; Rassweiler, J.; Kauczor, H. U.; Radeleff, B. A.; Pereira, P. L.

    2013-06-15

    Purpose. This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. Methods. We included 22 consecutive patients (3 women; age 74.2 {+-} 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 {+-} 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Results. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 {+-} 13.6 min and 43.7 {+-} 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 {+-} 8.8 months, local recurrence-free survival was 14.4 {+-} 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 {+-} 16.6 ml/min/1.73 m{sup 2} before RF ablation vs. 47.2 {+-} 11.9 ml/min/1.73 m{sup 2} after RF ablation; not significant). Conclusions. CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  12. Validation of a Cochlear Implant Patient-Specific Model of the Voltage Distribution in a Clinical Setting

    PubMed Central

    Nogueira, Waldo; Schurzig, Daniel; Büchner, Andreas; Penninger, Richard T.; Würfel, Waldemar

    2016-01-01

    Cochlear Implants (CIs) are medical implantable devices that can restore the sense of hearing in people with profound hearing loss. Clinical trials assessing speech intelligibility in CI users have found large intersubject variability. One possibility to explain the variability is the individual differences in the interface created between electrodes of the CI and the auditory nerve. In order to understand the variability, models of the voltage distribution of the electrically stimulated cochlea may be useful. With this purpose in mind, we developed a parametric model that can be adapted to each CI user based on landmarks from individual cone beam computed tomography (CBCT) scans of the cochlea before and after implantation. The conductivity values of each cochlea compartment as well as the weighting factors of different grounding modes have also been parameterized. Simulations were performed modeling the cochlea and electrode positions of 12 CI users. Three models were compared with different levels of detail: a homogeneous model (HM), a non-patient-specific model (NPSM), and a patient-specific model (PSM). The model simulations were compared with voltage distribution measurements obtained from the backward telemetry of the 12 CI users. Results show that the PSM produces the lowest error when predicting individual voltage distributions. Given a patient-specific geometry and electrode positions, we show an example on how to optimize the parameters of the model and how to couple it to an auditory nerve model. The model here presented may help to understand speech performance variability and support the development of new sound coding strategies for CIs. PMID:27933290

  13. Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

    PubMed

    Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

    2017-02-01

    This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity.

  14. Native Women at Risk: Addressing Cancer Prevention.

    ERIC Educational Resources Information Center

    Thiemann, Kay M. B.

    1994-01-01

    Discusses outcomes of a conference that brought together representatives from Indian tribes, state health departments, the Indian Health Service, the Mayo Clinic, and the American Cancer Society, to address the high rate of cervical cancer among American Indian women. Describes barriers to health care and plans to promote cancer screening among…

  15. Patient-specific finite-element simulation of the human cornea: a clinical validation study on cataract surgery.

    PubMed

    Studer, Harald P; Riedwyl, Hansjörg; Amstutz, Christoph A; Hanson, James V M; Büchler, Philippe

    2013-02-22

    The planning of refractive surgical interventions is a challenging task. Numerical modeling has been proposed as a solution to support surgical intervention and predict the visual acuity, but validation on patient specific intervention is missing. The purpose of this study was to validate the numerical predictions of the post-operative corneal topography induced by the incisions required for cataract surgery. The corneal topography of 13 patients was assessed preoperatively and postoperatively (1-day and 30-day follow-up) with a Pentacam tomography device. The preoperatively acquired geometric corneal topography - anterior, posterior and pachymetry data - was used to build patient-specific finite element models. For each patient, the effects of the cataract incisions were simulated numerically and the resulting corneal surfaces were compared to the clinical postoperative measurements at one day and at 30-days follow up. Results showed that the model was able to reproduce experimental measurements with an error on the surgically induced sphere of 0.38D one day postoperatively and 0.19D 30 days postoperatively. The standard deviation of the surgically induced cylinder was 0.54D at the first postoperative day and 0.38D 30 days postoperatively. The prediction errors in surface elevation and curvature were below the topography measurement device accuracy of ±5μm and ±0.25D after the 30-day follow-up. The results showed that finite element simulations of corneal biomechanics are able to predict post cataract surgery within topography measurement device accuracy. We can conclude that the numerical simulation can become a valuable tool to plan corneal incisions in cataract surgery and other ophthalmosurgical procedures in order to optimize patients' refractive outcome and visual function.

  16. Clinical evaluation of new automatic coronary-specific best cardiac phase selection algorithm for single-beat coronary CT angiography

    PubMed Central

    Xu, Lei; Fan, Zhanming; Liang, Junfu; Yan, Zixu; Sun, Zhonghua

    2017-01-01

    The aim of this study was to evaluate the workflow efficiency of a new automatic coronary-specific reconstruction technique (Smart Phase, GE Healthcare—SP) for selection of the best cardiac phase with least coronary motion when compared with expert manual selection (MS) of best phase in patients with high heart rate. A total of 46 patients with heart rates above 75 bpm who underwent single beat coronary computed tomography angiography (CCTA) were enrolled in this study. CCTA of all subjects were performed on a 256-detector row CT scanner (Revolution CT, GE Healthcare, Waukesha, Wisconsin, US). With the SP technique, the acquired phase range was automatically searched in 2% phase intervals during the reconstruction process to determine the optimal phase for coronary assessment, while for routine expert MS, reconstructions were performed at 5% intervals and a best phase was manually determined. The reconstruction and review times were recorded to measure the workflow efficiency for each method. Two reviewers subjectively assessed image quality for each coronary artery in the MS and SP reconstruction volumes using a 4-point grading scale. The average HR of the enrolled patients was 91.1±19.0bpm. A total of 204 vessels were assessed. The subjective image quality using SP was comparable to that of the MS, 1.45±0.85 vs 1.43±0.81 respectively (p = 0.88). The average time was 246 seconds for the manual best phase selection, and 98 seconds for the SP selection, resulting in average time saving of 148 seconds (60%) with use of the SP algorithm. The coronary specific automatic cardiac best phase selection technique (Smart Phase) improves clinical workflow in high heart rate patients and provides image quality comparable with manual cardiac best phase selection. Reconstruction of single-beat CCTA exams with SP can benefit the users with less experienced in CCTA image interpretation. PMID:28231322

  17. Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria.

    PubMed

    Pfaller, M A; Diekema, D J; Andes, D; Arendrup, M C; Brown, S D; Lockhart, S R; Motyl, M; Perlin, D S

    2011-06-01

    The CLSI established clinical breakpoints (CBPs) for caspofungin (CSF), micafungin (MCF) and anidulafungin (ANF) versus Candida. The same CBP (susceptible (S): MIC ≤ 2 mcg/ml; non-S: MIC > 2 mcg/ml) was applied to all echinocandins and species. More data now allow reassessment of these CBPs. We examined cases of echinocandin failure where both MICs and fks mutations were assessed; wild type (WT) MICs and epidemiological cutoff values (ECVs) for a large Candida collection; molecular analysis of fks hotspots for Candida with known MICs; and pharmacokinetic and pharmacodynamic (PK/PD) data. We applied these findings to propose new species-specific CBPs for echinocandins and Candida. Of 18 candidiasis cases refractory to echinocandins and with fks mutations, 28% (CSF), 58% (ANF) and 66% (MCF) had MICs in the S category using CBP of ≤ 2 mcg/ml, while 0-8% would be S using CBP of ≤ 0.25 mcg/ml. WT MIC distributions revealed ECV ranges of 0.03-0.25 mcg/ml for all major species except C. parapsilosis (1-4 mcg/ml) and C. guilliermondii (4-16 mcg/ml). Among Candida tested for fks mutations, only 15.7-45.1% of 51 mutants were detected using the CBP for NS of >2 mcg/ml. In contrast, a cutoff of >0.25 mcg/ml for C. albicans, C. tropicalis, C. krusei, and C. dubliniensis detected 85.6% (MCF) to 95.2% (CSF) of 21 mutant strains. Likewise, a cutoff of >0.12 mcg/ml for ANF and CSF and of >0.06 mcg/ml for MCF detected 93% (ANF) to 97% (CSF, MCF) of 30 mutant strains of C. glabrata. These data, combined with PK/PD considerations, support CBPs of ≤ 0.25 mcg/ml (S), 0.5 mcg/ml (I), ≥ 1 (R) for CSF/MCF/ANF and C. albicans, C. tropicalis and C. krusei and ≤ 2 mcg/ml (S), 4 mcg/ml (I), and ≥ 8 mcg/ml (R) for these agents and C. parapsilosis. The CBPs for ANF and CSF and C. glabrata are ≤ 0.12 mcg/ml (S), 0.25 mcg/ml (I), and ≥ 0.5 mcg/ml (R), whereas those for MCF are ≤ 0.06 mcg/ml (S), 0.12 mcg/ml (I), and ≥ 0.25 mcg/ml (R). New, species-specific CBPs for Candida

  18. The Reach Address Database (RAD)

    EPA Pesticide Factsheets

    The Reach Address Database (RAD) stores reach address information for each Water Program feature that has been linked to the underlying surface water features (streams, lakes, etc) in the National Hydrology Database (NHD) Plus dataset.

  19. Shortness of filum terminale represents an anatomical specific feature in fibromyalgia: a nuclear magnetic resonance and clinical study

    PubMed Central

    Mantia, Roberto; Di Gesù, Marco; Vetro, Angelo; Mantia, Fabrizio; Palma, Sebastiano; Iovane, Angelo

    2015-01-01

    Summary Background: we aimed to assess whether shortness of filum terminale (FT) can represent a specific feature of fibromyalgia. Therefore we investigated benefits coming from FT section with a mini-invasive technique in patients with fibromyalgia. Filum terminale disease (FD), described firstly in 1996, is consequence of an abnormal traction exerted on spinal cord since FT is shorter than usual. Fibromyalgia syndrome (FS) is featured by chronic widespread musculoskeletal pain associated with stiffness and extra-skeletal symptoms affecting many organs and systems. Filum terminale disease and fibromyalgia syndrome share common clinical features in at least one subset of patients. Methods: we evaluated 42 patients firstly diagnosed for FS and then re-evaluated by nuclear magnetic resonance. 38 out of 42 had also FD and 20 of them underwent surgical treatment, i.e., FT section according to Royo-Salvador technique. Results: after physical therapy, surgically treated patients showed significant improvement of symptoms in terms of reduction of pain and increment of quality of life, compared to group, which refused surgery and performed physical therapy only. Conclusion: we suggest that FT shortness can be considered one of predisposing causes for developing FS and that FD surgical treatment in patients with FS can improve overall treatment outcome. PMID:25878985

  20. Nonword repetition--a clinical marker for specific language impairment in Swedish associated with parents' language-related problems.

    PubMed

    Kalnak, Nelli; Peyrard-Janvid, Myriam; Forssberg, Hans; Sahlén, Birgitta

    2014-01-01

    First, we explore the performance of nonword repetition (NWR) in children with specific language impairment (SLI) and typically developing children (TD) in order to investigate the accuracy of NWR as a clinical marker for SLI in Swedish-speaking school-age children. Second, we examine the relationship between NWR, family aggregation, and parental level of education in children with SLI. A sample of 61 children with SLI, and 86 children with TD, aged 8-12 years, were administered an NWR test. Family aggregation, measured as the prevalence of language and/or literacy problems (LLP) in parents of the children with SLI, was based on family history interviews. The sensitivity and specificity of nonword repetition was analyzed in a binary logistic regression, cut-off values were established with ROC curves, and positive and negative likelihood ratios reported. Results from the present study show that NWR distinguishes well between Swedish-speaking school-children with and without SLI. We found 90.2% sensitivity and 97.7% specificity at a cut-off level of -2 standard deviations for binary scoring of nonwords. Differences between the SLI and TD groups showed large effect sizes for the two scoring measures binary (d = 2.11) and percent correct consonants (PCC) (d = 1.79). The children with SLI were split into two subgroups: those with no parents affected with LLP (n = 12), and those with one or both parents affected (n = 49). The subgroup consisting of affected parents had a significantly lower score on NWR binary (p = .037), and there was a great difference between the subgroups (d = 0.7). When compared to the TD group, the difference from the subgroup with affected parents was almost one standard deviation larger (d = 2.47) than the difference from the TD to the subgroup consisting of non-affected parents (d = 1.57). Our study calls for further exploration of the complex interaction between family aggregation, language input, and phenotypes

  1. A region addresses patient safety.

    PubMed

    Feinstein, Karen Wolk; Grunden, Naida; Harrison, Edward I

    2002-06-01

    The Pittsburgh Regional Healthcare Initiative (PRHI) is a coalition of 35 hospitals, 4 major insurers, more than 30 major and small-business health care purchasers, dozens of corporate and civic leaders, organized labor, and partnerships with state and federal government all working together to deliver perfect patient care throughout Southwestern Pennsylvania. PRHI believes that in pursuing perfection, many of the challenges facing today's health care delivery system (eg, waste and error in the delivery of care, rising costs, frustration and shortage among clinicians and workers, financial distress, overcapacity, and lack of access to care) will be addressed. PRHI has identified patient safety (nosocomial infections and medication errors) and 5 clinical areas (obstetrics, orthopedic surgery, cardiac surgery, depression, and diabetes) as ideal starting points. In each of these areas of work, PRHI partners have assembled multifacility/multidisciplinary groups charged with defining perfection, establishing region-wide reporting systems, and devising and implementing recommended improvement strategies and interventions. Many design and conceptual elements of the PRHI strategy are adapted from the Toyota Production System and its Pittsburgh derivative, the Alcoa Business System. PRHI is in the proof-of-concept phase of development.

  2. Automated measurement of printer effective addressability

    NASA Astrophysics Data System (ADS)

    Cooper, Brian E.; Eid, Ahmed H.; Rippetoe, Edward E.

    2014-01-01

    When evaluating printer resolution, addressability is a key consideration. Addressability defines the maximum number of spots or samples within a given distance, independent of the size of the spots when printed. Effective addressability is the addressability demonstrated by the final, printed output. It is the minimum displacement possible between the centers of printed objects. In this paper, we present a measurement procedure for effective addressability that offers an automated way to experimentally determine the addressability of the printed output. It requires printing, scanning, and measuring a test target. The effective addressability test target contains two types of elements, repeated to fill the page: fiducial lines and line segments. The fiducial lines serve as a relative reference for the incremental displacements of the individual line segments, providing a way to tolerate larger-scale physical distortions in the printer. An ordinary reflection scanner captures the printed test target. By rotating the page on the scanner, it is possible to measure effective addressability well beyond the scanner's sampling resolution. The measurement algorithm computes the distribution of incremental displacements, forming either a unimodal or bimodal histogram. In the latter case, the mean of the second (non-zero) peak indicates the effective addressability. In the former case, the printer successfully rendered the target's resolution, requiring another iteration of the procedure after increasing the resolution of the test target. The algorithm automatically estimates whether the histogram is unimodal or bimodal and computes parameters describing the quality of the measured histogram. Several experiments have refined the test target and measurement procedure, including two round-robin evaluations by the ISO WG4 committee. Results include an analysis of approximately 150 printed samples. The effective addressability attribute and measurement procedure are included in

  3. Direct estimation of cause-specific mortality fractions from verbal autopsies: multisite validation study using clinical diagnostic gold standards

    PubMed Central

    2011-01-01

    Background Verbal autopsy (VA) is used to estimate the causes of death in areas with incomplete vital registration systems. The King and Lu method (KL) for direct estimation of cause-specific mortality fractions (CSMFs) from VA studies is an analysis technique that estimates CSMFs in a population without predicting individual-level cause of death as an intermediate step. In previous studies, KL has shown promise as an alternative to physician-certified verbal autopsy (PCVA). However, it has previously been impossible to validate KL with a large dataset of VAs for which the underlying cause of death is known to meet rigorous clinical diagnostic criteria. Methods We applied the KL method to adult, child, and neonatal VA datasets from the Population Health Metrics Research Consortium gold standard verbal autopsy validation study, a multisite sample of 12,542 VAs where gold standard cause of death was established using strict clinical diagnostic criteria. To emulate real-world populations with varying CSMFs, we evaluated the KL estimations for 500 different test datasets of varying cause distribution. We assessed the quality of these estimates in terms of CSMF accuracy as well as linear regression and compared this with the results of PCVA. Results KL performance is similar to PCVA in terms of CSMF accuracy, attaining values of 0.669, 0.698, and 0.795 for adult, child, and neonatal age groups, respectively, when health care experience (HCE) items were included. We found that the length of the cause list has a dramatic effect on KL estimation quality, with CSMF accuracy decreasing substantially as the length of the cause list increases. We found that KL is not reliant on HCE the way PCVA is, and without HCE, KL outperforms PCVA for all age groups. Conclusions Like all computer methods for VA analysis, KL is faster and cheaper than PCVA. Since it is a direct estimation technique, though, it does not produce individual-level predictions. KL estimates are of similar

  4. Optimal insemination and replacement decisions to minimize the cost of pathogen-specific clinical mastitis in dairy cows.

    PubMed

    Cha, E; Kristensen, A R; Hertl, J A; Schukken, Y H; Tauer, L W; Welcome, F L; Gröhn, Y T

    2014-01-01

    Mastitis is a serious production-limiting disease, with effects on milk yield, milk quality, and conception rate, and an increase in the risk of mortality and culling. The objective of this study was 2-fold: (1) to develop an economic optimization model that incorporates all the different types of pathogens that cause clinical mastitis (CM) categorized into 8 classes of culture results, and account for whether the CM was a first, second, or third case in the current lactation and whether the cow had a previous case or cases of CM in the preceding lactation; and (2) to develop this decision model to be versatile enough to add additional pathogens, diseases, or other cow characteristics as more information becomes available without significant alterations to the basic structure of the model. The model provides economically optimal decisions depending on the individual characteristics of the cow and the specific pathogen causing CM. The net returns for the basic herd scenario (with all CM included) were $507/cow per year, where the incidence of CM (cases per 100 cow-years) was 35.6, of which 91.8% of cases were recommended for treatment under an optimal replacement policy. The cost per case of CM was $216.11. The CM cases comprised (incidences, %) Staphylococcus spp. (1.6), Staphylococcus aureus (1.8), Streptococcus spp. (6.9), Escherichia coli (8.1), Klebsiella spp. (2.2), other treated cases (e.g., Pseudomonas; 1.1), other not treated cases (e.g., Trueperella pyogenes; 1.2), and negative culture cases (12.7). The average cost per case, even under optimal decisions, was greatest for Klebsiella spp. ($477), followed by E. coli ($361), other treated cases ($297), and other not treated cases ($280). This was followed by the gram-positive pathogens; among these, the greatest cost per case was due to Staph. aureus ($266), followed by Streptococcus spp. ($174) and Staphylococcus spp. ($135); negative culture had the lowest cost ($115). The model recommended treatment for

  5. Specifics of the renal abscess in nephrology: observations of a clinic from a county hospital in Western Romania.

    PubMed

    Velciov, Silvia; Gluhovschi, Gh; Trandafirescu, V; Petrica, Ligia; Bozdog, Gh; Gluhovschi, Cristina; Bob, F; Gădălean, F; Bobu, M

    2011-01-01

    During the last years renal abscesses are being diagnosed with increasing frequency in Nephrology departments. Progresses achieved in imaging procedures permit a timely diagnosis of renal abscesses. At the same time modern antibiotic therapies permit the treatment of this disease in Nephrology departments. In the current paper we present some specifics of renal abscess management encountered in a Nephrology department in western Romania. We performed a retrospective analysis of 2793 patients with upper urinary tract infection hospitalised during 2002-2009 in our Nephrology Department, of whom 44 showed renal abscesses. Uropathic factors were identified less frequently, in 28% of the renal abscess cases, compared to cases in the literature where these have been reported in over 50% of the patients. General predisposing conditions were pregnancy in 7%, postviral cirrhosis in 4%, diabetes mellitus in 4%, surgically single kidney in 2%, polycystic kidney disease in 4% of the patients. We diagnosed renal abscesses in relatively young patients (mean age 38.73 +/- 19.64), fact that could be due to a decreased immune resistance of these patients. Renal function impairment was present in 17% of the patients. Urine cultures were positive in 25% with a predominance of E. coli and rarely of other germs (e.g. Citrobacter and Candida albicans). Therapy consisted of broad spectrum antibiotics applied to all patients. Two patients required the insertion of double J catheter. Five patients (11%) were referred to the Urology Department, where one patient underwent nephrectomy. Renal abscess was diagnosed and treated in the majority of cases in the Nephrology Department, and only in special cases is a referral to the Urology clinic required.

  6. Analog specificity of the thyrotropin-releasing hormone receptor in the central nervous system: possible clinical implications

    SciTech Connect

    Hawkins, E.F.; Engel, W.K.

    1985-02-11

    TRH has rapid-onset (30 sec), slow-offset (1-12 days) clinical benefit in patients with amyotrophic lateral sclerosis and other motor neuron disorders. This benefit is probably receptor-mediated and may have at least 2 components. To obtain a better understanding of the various responses to TRH of the spinal lower motor neurons (LMNs) in patients, and possibly to help guide selection of additional therapeutic agents, the authors utilized rat CNS (spinal-cord and brain membranes) to analyze the ability of certain molecules to inhibit specific binding of (/sup 3/H)methyl TRH ((/sup 3/H)MeTRH) to the TRH receptor. They found: a) lack of high-affinity binding of the TRH-analog DN-1417 by spinal-cord and brain TRH receptor, despite its known strong TRH-like action physiologically on LMNs; b) lack of high-affinity binding of the TRH-product cyclo(His-Pro) by spinal cord and brain TRH receptor despite its having some strong TRH-like physiologic actions on the CNS; and c) lack of any identifiable high-affinity receptor for cyclo(His-Pro) in spinal cord and brain. From these data the authors hypothesize that the acute transmitter-like action of DN-1417, TRH, and possibly other TRH-analogs and products on LMNs is via a non-TRH receptor, such as an amine or amino acid neurotransmitter receptor, e.g. a 5-hydroxytryptamine receptor. They further postulate that the CNS TRH-receptor may modulate a trophic-like influence of TRH on LMNs.

  7. Pharmacological Levels of Withaferin A (Withania somnifera) Trigger Clinically Relevant Anticancer Effects Specific to Triple Negative Breast Cancer Cells

    PubMed Central

    Szarc vel Szic, Katarzyna; Op de Beeck, Ken; Ratman, Dariusz; Wouters, An; Beck, Ilse M.; Declerck, Ken; Heyninck, Karen; Fransen, Erik; Bracke, Marc; De Bosscher, Karolien; Lardon, Filip; Van Camp, Guy; Berghe, Wim Vanden

    2014-01-01

    Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy

  8. Age- and sex-specific estimation of dose to a normal thyroid from clinical administration of iodine-131

    SciTech Connect

    Killough, G.G.; Eckerman, K.F.

    1986-09-01

    This report describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to /sup 131/I in diagnostic and therapeutic procedures. In most cases, the data available consisted of the patient's age at the time of administration, the patient's sex, the quantity of activity administered, the clinically determined uptake of radioiodine by the thyroid, and the time after administration at which the uptake was determined. The model was made to conform to these data requirements by the use of age-specific estimates of the biological half-time of iodine in the thyroid and an age- and sex-dependent representation of the mass of the thyroid. Also, it was assumed that the thyroid burden was maximum at 24 hours after administration (the /sup 131/I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K x (exp(-..mu../sub 1/t) - exp(-..mu../sub 2/t)) ..mu..Ci where ..mu../sub i/ = lambda/sub r/ + lambda/sub i//sup b/ (i = 1, 2), lambda/sub r/ is the radiological decay-rate coefficient, and the lambda/sub i//sup b/ are biological removal-rate coefficients. The values of lambda/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time of maximum uptake and the eventual biological loss rate (through which age dependence enters). An addendum (Appendix C) extends the method to other radioiodines and gives age- and sex-dependent dose conversion factors for most isotopes.

  9. Addressing Psychosocial Factors with Library Mentoring

    ERIC Educational Resources Information Center

    Farrell, Bridget; Alabi, Jaena; Whaley, Pambanisha; Jenda, Claudine

    2017-01-01

    The majority of articles on mentoring in the library and information science field address career development by emphasizing the orientation process for new librarians and building the requisite skills for a specific job. Few articles deal with the psychological and social challenges that many early-career and minority librarians face, which can…

  10. Rational Rhymes for Addressing Common Childhood Issues

    ERIC Educational Resources Information Center

    Warren, Jeffrey M.

    2011-01-01

    Music-based interventions are valuable tools counselors can use when working with children. Specific types of music-based interventions, such as songs or rhymes, can be especially pertinent in addressing the thoughts, feelings, and behaviors of children. Rational-emotive behavior therapy (REBT) provides a therapeutic framework that encourages…

  11. Hematology and Clinical Chemistry Measures During and After Pregnancy and Age- and Sex-Specific Reference Intervals in African Green Monkeys (Chlorocebus aethiops sabaeus).

    PubMed

    Chichester, Lee; Gee, Melaney K; Jorgensen, Matthew J; Kaplan, Jay R

    2015-07-01

    Clinical decisions and experimental analyses often involve the assessment of hematology and clinical chemistry. Using clinical pathology to assess the health status of NHP in breeding colonies or data from studies than involve pregnancy can often be complicated by pregnancy status. This study had 2 objectives regarding the hematology and clinical chemistry of African green monkeys (AGM, Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum animals with nonpregnant, nonlactating animals and 2) to create age- and sex-specific reference intervals. Subjects in this study were 491 AGM from the Vervet Research Colony of the Wake Forest University Primate Center. Results indicated that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus, sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC, neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and the postpartum period. Age- and sex-specific reference intervals consistent with guidelines from the American Society for Veterinary Clinical Pathology were established and further expand the understanding of how to define health in AGM on the basis of clinical pathology. The combination of understanding the changes that occur in pregnancy and postpartum and expansive reference intervals will help guide clinical and experimental decisions.

  12. Hematology and Clinical Chemistry Measures During and After Pregnancy and Age- and Sex-Specific Reference Intervals in African Green Monkeys (Chlorocebus aethiops sabaeus)

    PubMed Central

    Chichester, Lee; Gee, Melaney K; Jorgensen, Matthew J; Kaplan, Jay R

    2015-01-01

    Clinical decisions and experimental analyses often involve the assessment of hematology and clinical chemistry. Using clinical pathology to assess the health status of NHP in breeding colonies or data from studies than involve pregnancy can often be complicated by pregnancy status. This study had 2 objectives regarding the hematology and clinical chemistry of African green monkeys (AGM, Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum animals with nonpregnant, nonlactating animals and 2) to create age- and sex-specific reference intervals. Subjects in this study were 491 AGM from the Vervet Research Colony of the Wake Forest University Primate Center. Results indicated that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus, sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC, neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and the postpartum period. Age- and sex-specific reference intervals consistent with guidelines from the American Society for Veterinary Clinical Pathology were established and further expand the understanding of how to define health in AGM on the basis of clinical pathology. The combination of understanding the changes that occur in pregnancy and postpartum and expansive reference intervals will help guide clinical and experimental decisions. PMID:26224434

  13. Clinical and anti-HLA antibody profile of nine renal transplant recipients with failed grafts: donor-specific and non-donor-specific antibody development.

    PubMed

    Rebellato, Lorita M; Ozawa, Miyuki; Verbanac, Kathryn M; Catrou, Paul; Haisch, Carl E; Terasaki, Paul I

    2006-01-01

    This study applied the single antigen microsphere technology to the retrospective analysis of sequential post-transplant serum samples in the context of the patient's clinical course. Detailed information on nine of the study patients was presented as representative of the larger cohort and illustrative of different patterns of anti-HLA antibody development and different clinical scenarios that culminated in graft failure. Our major observations are summarized as follows: 1. These data confirm the high sensitivity of the single antigen bead method: In some patients, DSA and NDSA that were undetected by standard methods were found pre-transplant and in sequential post-transplant samples. 2. The precise role that anti-HLA antibody plays in a particular rejection are complicated in cases in which humoral rejection is not diagnosed in the biopsy: The possible involvement of ADCC and mechanisms involving an indirect role for antibody in the rejection process should be carefully investigated. 3. Although anti-HLA antibodies are associated with graft rejection, the time interval between detection and rejection can vary dramatically between patients. Both DSA and NDSA can be adsorbed by the graft and erratically detected in the circulation, in some cases remaining undetected until nephrectomy. 4. Anti-HLA antibody strengths often fluctuate widely over a patient's clinical course, with de novo DSA generally of greater strength than de novo NDSA. 5. In addition to DSA, we have observed the consistent induction of diverse, cross-reactive NDSA. This occurs not only during the post-transplant course but also after graft failure, when immunosuppression is tapered prior to nephrectomy. Our data support further studies to evaluate the value of prospective monitoring of anti-HLA antibodies to better understand the place of anti-HLA antibodies in acute rejection. This may improve our ability to reverse some acute rejection episodes. Since acute rejection has been considered a

  14. CONTENT-ADDRESSABLE MEMORY SYSTEMS,

    DTIC Science & Technology

    The utility of content -addressable memories (CAM’s) within a general purpose computing system is investigated. Word cells within CAM may be...addressed by the character of all or a part of cell contents . Multimembered sets of word cells may be addressed simultaneously. The distributed logical...package is developed which allows simulation of CAM commands within job programs run on the IBM 7090 and derives tallies of execution times corresponding to a particular realization of a CAM system . (Author)

  15. Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study

    PubMed Central

    Markar, Sheraz R; Mavroveli, Stella; Petrides, Konstantinos V; Scarpa, Marco; Christophe, Veronique; Castoro, Carlo; Mariette, Christophe; Lagergren, Pernilla; Hanna, George B

    2016-01-01

    Introduction Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. Objectives To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. Methods and analysis This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. Ethics and dissemination NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal. PMID:27798009

  16. What Specific Areas Must a Hazardous Waste Permit Address?

    EPA Pesticide Factsheets

    Hazardous waste permits provide treatment, storage, and disposal facilities (TSDFs) with the legal authority to treat, store, or dispose of hazardous waste and detail how the facility must comply with the regulations

  17. Addressing the Moral Agency of Culturally Specific Care Perspectives

    ERIC Educational Resources Information Center

    Johnson, Chrystal S.

    2011-01-01

    Cultural Historical Activity Theory (CHAT), as a culturally sensitive framework, realises the totality of caring in context. Few, if any, investigations into caring have articulated CHAT as a feasible mode of inquiry for inserting the cultural perspectives of both the researcher and the researched. This article elucidates CHAT as an intelligible…

  18. Addressing Asthma Health Disparities: A Multilevel Challenge

    PubMed Central

    Canino, Glorisa; McQuaid, Elizabeth L.; Rand, Cynthia S.

    2009-01-01

    Substantial research has documented pervasive disparities in the prevalence, severity, and morbidity of asthma among minority populations compared to non-Latino whites. The underlying causes of these disparities are not well understood, and as a result, the leverage points to address them remain unclear. A multilevel framework for integrating research in asthma health disparities is proposed in order to advance both future research and clinical practice. The components of the proposed model include health care policies and regulations, operation of the health care system, provider/clinician-level factors, social/environmental factors, and individual/family attitudes and behaviors. The body of research suggests that asthma disparities have multiple, complex and inter-related sources. Disparities occur when individual, environmental, health system, and provider factors interact with one another over time. Given that the causes of asthma disparities are complex and multilevel, clinical strategies to address these disparities must therefore be comparably multilevel and target many aspects of asthma care. Clinical Implications: Several strategies that could be applied in clinical settings to reduce asthma disparities are described including the need for routine assessment of the patient’s beliefs, financial barriers to disease management, and health literacy, and the provision of cultural competence training and communication skills to health care provider groups. PMID:19447484

  19. Using clinically acquired MRI to construct age-specific ADC atlases: Quantifying spatiotemporal ADC changes from birth to 6-year old.

    PubMed

    Ou, Yangming; Zöllei, Lilla; Retzepi, Kallirroi; Castro, Victor; Bates, Sara V; Pieper, Steve; Andriole, Katherine P; Murphy, Shawn N; Gollub, Randy L; Grant, Patricia Ellen

    2017-03-31

    Diffusion imaging is critical for detecting acute brain injury. However, normal apparent diffusion coefficient (ADC) maps change rapidly in early childhood, making abnormality detection difficult. In this article, we explored clinical PACS and electronic healthcare records (EHR) to create age-specific ADC atlases for clinical radiology reference. Using the EHR and three rounds of multiexpert reviews, we found ADC maps from 201 children 0-6 years of age scanned between 2006 and 2013 who had brain MRIs with no reported abnormalities and normal clinical evaluations 2+ years later. These images were grouped in 10 age bins, densely sampling the first 1 year of life (5 bins, including neonates and 4 quarters) and representing the 1-6 year age range (an age bin per year). Unbiased group-wise registration was used to construct ADC atlases for 10 age bins. We used the atlases to quantify (a) cross-sectional normative ADC variations; (b) spatiotemporal heterogeneous ADC changes; and (c) spatiotemporal heterogeneous volumetric changes. The quantified age-specific whole-brain and region-wise ADC values were compared to those from age-matched individual subjects in our study and in multiple existing independent studies. The significance of this study is that we have shown that clinically acquired images can be used to construct normative age-specific atlases. These first of their kind age-specific normative ADC atlases quantitatively characterize changes of myelination-related water diffusion in the first 6 years of life. The quantified voxel-wise spatiotemporal ADC variations provide standard references to assist radiologists toward more objective interpretation of abnormalities in clinical images. Our atlases are available at https://www.nitrc.org/projects/mgh_adcatlases. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  20. [Specific clinical and immunological features of chronic diseases of the nasal-associated lymphoid tissue in the children].

    PubMed

    Beniova, S N; Taranova, S V; Babko, S V

    2014-01-01

    The objective of the present work was to study the structure, clinical, and immunological features of various etiological variants of chronic diseases of the nasal-associated lymphoid tissue in the children. A total of 142 children at the age from 3 to 7 years presenting with this pathological condition were available for the observation. The study revealed differences in the clinical course of the disease and the cytokine response (IL-6, Ril-6, TNF, sYNFR55, sTNFR75) at the local and systemic levels for different pathogens (S. aureus, S. pneumoniae, S. pyrogenes).

  1. Addressing language barriers to healthcare in India.

    PubMed

    Narayan, Lalit

    2013-01-01

    In spite of a growing recognition of the importance of doctor-patient communication, the issue of language barriers to healthcare has received very little attention in India. The Indian population speaks over 22 major languages with English used as the lingua franca for biomedicine. Large-scale internal migration has meant that health workers are encountering increasing instances of language discordance within clinical settings. Research done predominantly in the West has shown language discordance to significantly affect access to care, cause problems of comprehension and adherence, and decrease the satisfaction and quality of care. Addressing language barriers to healthcare in India requires a stronger political commitment to providing non-discriminatory health services, especially to vulnerable groups such as illiterate migrant workers. Research will have to address three broad areas: the ways in which language barriers affect health and healthcare, the efficacy of interventions to overcome language barriers, and the costs of language barriers and efforts to overcome them. There is a need to address such barriers in health worker education and clinical practice. Proven strategies such as hiring multilingual healthcare workers, providing language training to health providers, employing in situ translators or using telephone interpretation services will have to be evaluated for their appropriateness to the Indian context. Internet-based initiatives, the proliferation of mobile phones and recent advances in machine translation promise to contribute to the solution.

  2. An Automated System for Generating Situation-Specific Decision Support in Clinical Order Entry from Local Empirical Data

    ERIC Educational Resources Information Center

    Klann, Jeffrey G.

    2011-01-01

    Clinical Decision Support is one of the only aspects of health information technology that has demonstrated decreased costs and increased quality in healthcare delivery, yet it is extremely expensive and time-consuming to create, maintain, and localize. Consequently, a majority of health care systems do not utilize it, and even when it is…

  3. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure.

    PubMed

    Nguyen, Tanya T; Glass, Leila; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-08-01

    Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8-16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE-, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure.

  4. Presence of specific MHC Class II expressed alleles associates with clinical disease in ovine progressive pneumonia virus (OPPV) infected sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genetic tool hypothesized to predict which OPPV infected sheep will progress to debilitating clinical disease is MHC Class II Ovis aries (Ovar)-DRB1. Previously, fifteen Ovar-DRB1 beta 1 expressed alleles were identified in a ewe-lamb flock of 32 originating from an Idaho flock using RT-PCR, clon...

  5. Addressing Family Smoking in Child Health Care Settings.

    PubMed

    Hall, Nicole; Hipple, Bethany; Friebely, Joan; Ossip, Deborah J; Winickoff, Jonathan P

    2009-08-01

    OBJECTIVE: To discuss strategies for integrating evidence-based tobacco use screening, cessation assistance, and referral to outside services into visits with families in outpatient child health care settings. METHODS: Presentation of counseling scenarios used in the Clinical Effort Against Secondhand Smoke Exposure (CEASE) training video and commentary. RESULTS: Demonstrated strategies include: eliciting information about interest and readiness to quit smoking, respectfully setting an agenda to discuss smoking, tailoring advice and education to the specific circumstances, keeping the dialogue open, prescribing cessation medication, helping the smoker set an action plan for cessation, enrolling the smoker in free telephone counseling through the state quitline, and working with family members to establish a completely smoke-free home and car. Video demonstrations of these techniques are available at www.ceasetobacco.org. CONCLUSION: Child health care clinicians have a unique opportunity to address family smoking and can be most effective by adapting evidence-based tobacco cessation counseling strategies for visits in the pediatric setting.

  6. Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia

    PubMed Central

    Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

    2014-01-01

    Background Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Key Results According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions & Inferences Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. PMID:24909661

  7. Use of a new tandem cation/anion exchange system with clinical-scale generators provides high specific volume solutions of technetium-99m and rhenium-188

    SciTech Connect

    Knapp, F.R. Jr.; Beets, A.L.; Mirzadeh, S.; Guhlke, S. |

    1998-03-01

    In this paper the authors describe the first application of a simple and inexpensive post elution tandem cation-anion exchange column system which is based on generator elution with salts of weak acids such as ammonium acetate instead of saline solution to provide very high specific volume solutions of technetium-99m and rhenium-188 from clinical scale molybdenum-99/technetium-99m generator prepared from low specific activity (n,y) molybdenum-99, and tungsten-188/rhenium-188 generators, respectively. Initial passage of the bolus through a strong cation exchange cartridge converts the ammonium acetate to acetic acid which is essentially not ionized at the acidic pH, allowing specific subsequent amine type (QMA SepPak{trademark}) anion exchange cartridge column trapping of the microscopic levels of the pertechnetate or perrhenate. Subsequent elution of the anion cartridge with a small volume (< 1 mL) of saline then provides high specific volume solutions of technetium-99m by concentration of the high eluant volumes obtained by elution of clinical-scale (1 Ci) generators. This new approach also works very effectively to obtain high specific volume solutions of rhenium-188 (> 500 mCi/mL) from the alumina-based tungsten-188/rhenium-188 generator.

  8. High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome.

    PubMed

    Kasprowicz, Victoria; Schulze Zur Wiesch, Julian; Kuntzen, Thomas; Nolan, Brian E; Longworth, Steven; Berical, Andrew; Blum, Jenna; McMahon, Cory; Reyor, Laura L; Elias, Nahel; Kwok, William W; McGovern, Barbara G; Freeman, Gordon; Chung, Raymond T; Klenerman, Paul; Lewis-Ximenez, Lia; Walker, Bruce D; Allen, Todd M; Kim, Arthur Y; Lauer, Georg M

    2008-03-01

    We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8(+) and CD4(+) T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection.

  9. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases.

    PubMed

    Harris, Philip A; Berger, Scott B; Jeong, Jae U; Nagilla, Rakesh; Bandyopadhyay, Deepak; Campobasso, Nino; Capriotti, Carol A; Cox, Julie A; Dare, Lauren; Dong, Xiaoyang; Eidam, Patrick M; Finger, Joshua N; Hoffman, Sandra J; Kang, James; Kasparcova, Viera; King, Bryan W; Lehr, Ruth; Lan, Yunfeng; Leister, Lara K; Lich, John D; MacDonald, Thomas T; Miller, Nathan A; Ouellette, Michael T; Pao, Christina S; Rahman, Attiq; Reilly, Michael A; Rendina, Alan R; Rivera, Elizabeth J; Schaeffer, Michelle C; Sehon, Clark A; Singhaus, Robert R; Sun, Helen H; Swift, Barbara A; Totoritis, Rachel D; Vossenkämper, Anna; Ward, Paris; Wisnoski, David D; Zhang, Daohua; Marquis, Robert W; Gough, Peter J; Bertin, John

    2017-02-23

    RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.

  10. Comparison of clinical categories for Escherichia coli harboring specific qnr and chromosomal-mediated fluoroquinolone resistance determinants according to CLSI and EUCAST.

    PubMed

    Machuca, Jesús; Briales, Alejandra; Díaz-de-Alba, Paula; Martínez-Martínez, Luis; Rodríguez-Martínez, José-Manuel; Pascual, Álvaro

    2016-03-01

    EUCAST breakpoints are more restrictive than those defined by CLSI. This study highlights the discrepancies between CLSI and EUCAST in a well characterized isogenic Escherichia coli collection and their correlations with specific quinolone resistance mechanisms. The greatest number of discrepancies was observed in strains containing 2-4 resistance mechanisms (MIC values on the borderline of clinical resistance). Bearing in mind that quinolones are concentration dependent antimicrobial agents, small changes in MIC may have relevant consequences for treatment outcomes.

  11. Genomic Diversity of Burkholderia pseudomallei Clinical Isolates: Subtractive Hybridization Reveals a Burkholderia mallei-Specific Prophage in B. pseudomallei 1026b

    DTIC Science & Technology

    2004-06-01

    Burkholderia strains used in this study included Burkholderia cepacia LMG 1222 (44), Burkholderia multivorans C5568, B. multivorans LMG 18823 (44...and experimentally useful panel of strains from the Burkholderia cepacia complex. J. Clin. Microbiol. 38:910–913. 45. Manzeniuk, O. I., N. V... Burkholderia pseudomallei Clinical Isolates: Subtractive Hybridization Reveals a Burkholderia mallei-Specific Prophage in B. pseudomallei 1026b David

  12. Genomic Diversity of Burkholderia pseudomallei Clinical Isolates: Subtractive Hybridization Reveals a Burkholderia mallei-Specific Propage in B. pseudomallei 1026b

    DTIC Science & Technology

    2004-06-01

    in this study included Burkholderia cepacia LMG 1222 (44), Burkholderia multivorans C5568, B. multivorans LMG 18823 (44), Burkholderia cenocepacia... Burkholderia cepacia complex. J. Clin. Microbiol. 38:910–913. 45. Manzeniuk, O. I., N. V. Volozhantsev, and E. A. Svetoch. 1994. Identification of Pseudomonas...diversity of Burkholderia pseudomallei clinical isolates: subtractive hybridization reveals a Burkholderia mallei-specific prophage in B. pseudomallei 1026b

  13. Task specific evaluation of clinical full field digital mammography systems using the Fourier definition of the Hotelling observer SNR

    NASA Astrophysics Data System (ADS)

    Liu, Haimo; Badano, Aldo; Benevides, Luis; Chakrabarti, Kish; Kaczmarek, Richard V.; Kyprianou, Iacovos S.

    2010-04-01

    Pixel Signal to Noise Ratio (SNR) is a commonly used clinical metric for evaluating mammography. However, we showed in this paper, the pixel SNR can produce misleading system detectability when image processing is utilized. We developed a simple, reliable and clinically applicable methodology to evaluate mammographic imaging systems using a task SNR that accounts for the imaging system performance in the presence of the patient. We used the Hotelling observer method in spatial frequency domain to calculate the task SNR of small disk test objects embedded in the breast tissue-equivalent series (BRTES) phantom for GE Senographe DS Full Field Digital Mammography (FFDM) system. The results were compared to the calculation of pixel SNR. We calculated the Hotelling observer SNR by estimating the generalized modulation transfer function (GMTF), generalized normalized noise power spectrum (GNNPS) and generalized noise equivalent quanta (GNEQ) in the presence of the breast phantom. The task SNR we calculated increased with the square root of the exposure as expected. Furthermore, we showed that the method is stable under image processing. The task SNR is a more reliable method for evaluating the performance of imaging systems especially under realistic clinical conditions where patient equivalent phantoms or image processing is used.

  14. Addressing Risks to Advance Mental Health Research

    PubMed Central

    Iltis, Ana S.; Misra, Sahana; Dunn, Laura B.; Brown, Gregory K.; Campbell, Amy; Earll, Sarah A.; Glowinski, Anne; Hadley, Whitney B.; Pies, Ronald; DuBois, James M.

    2015-01-01

    Objective Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards (IRBs) may reject study designs that appear too risky. This can discourage needed research, particularly in higher risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research. This article provides mental health researchers with practical approaches to: 1) identify and define various intrinsic research risks; 2) communicate these risks to others (e.g., potential participants, regulatory bodies, society); 3) manage these risks during the course of a study; and 4) justify the risks. Methods As part of a National Institute of Mental Health (NIMH)-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. IRB review was not required because there were no human subjects. The NIMH played no role in developing or reviewing the manuscript. Results Challenges, current data, practical strategies, and topics for future research are addressed for each of four key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks. Conclusions Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain IRB approval. PMID:24173618

  15. The Non-Word Repetition Task as a Clinical Marker of Specific Language Impairment in Spanish-Speaking Children

    ERIC Educational Resources Information Center

    Girbau, Dolors

    2016-01-01

    Forty native Spanish-speaking children (age 8;0-10;3), 20 with Specific Language Impairment (SLI) and 20 with Typical Language Development (TLD), received a battery of psycholinguistic tests, IQ, hearing screenings, and the Spanish Non-word Repetition Task (NRT). The children's repetition of 20 non-words was scored. The percentage of correct…

  16. One-Session Treatment of Specific Phobias in Youth: A Randomized Clinical Trial in the United States and Sweden

    ERIC Educational Resources Information Center

    Ollendick, Thomas H.; Ost, Lars-Goran; Reuterskiold, Lena; Costa, Natalie; Cederlund, Rio; Sirbu, Cristian; Davis, Thompson E., III; Jarrett, Matthew A.

    2009-01-01

    One hundred and ninety-six youth, ages 7-16, who fulfilled "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.) criteria for various specific phobias were randomized to a one-session exposure treatment, education support treatment, or a wait list control group. After the waiting period, the wait list participants were…

  17. Developmental Course of Deprivation-Specific Psychological Patterns: Early Manifestations, Persistence to Age 15, and Clinical Features

    ERIC Educational Resources Information Center

    Kreppner, Jana; Kumsta, Robert; Rutter, Michael; Beckett, Celia; Castle, Jennifer; Stevens, Suzanne; Sonuga-Barke, Edmund J.

    2010-01-01

    In chapter IV, the authors focused on their findings on the developmental course of deprivation-specific psychological patterns (DSPs). The authors rediscussed the syndrome concept in the light of two main considerations. First, the findings indicated substantial overlap among the four postulated DSPs at 15 years including CI and I/O before…

  18. Naming Speed as a Clinical Marker in Predicting Basic Calculation Skills in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Kleemans, Tijs; Segers, Eliane; Verhoeven, Ludo

    2012-01-01

    The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on…

  19. Every Other Day. Keynote Address.

    ERIC Educational Resources Information Center

    Tiller, Tom

    Schools need to be reoriented and restructured so that what is taught and learned, and the way in which it is taught and learned, are better integrated with young people's real-world experiences. Many indicators suggest that the meaningful aspects of school have been lost in the encounter with modern times. The title of this address--"Every…

  20. Agenda to address climate change

    SciTech Connect

    1998-10-01

    This document looks at addressing climate change in the 21st century. Topics covered are: Responding to climate change; exploring new avenues in energy efficiency; energy efficiency and alternative energy; residential sector; commercial sector; industrial sector; transportation sector; communities; renewable energy; understanding forests to mitigate and adapt to climate change; the Forest Carbon budget; mitigation and adaptation.

  1. Addressing Phonological Questions with Ultrasound

    ERIC Educational Resources Information Center

    Davidson, Lisa

    2005-01-01

    Ultrasound can be used to address unresolved questions in phonological theory. To date, some studies have shown that results from ultrasound imaging can shed light on how differences in phonological elements are implemented. Phenomena that have been investigated include transitional schwa, vowel coalescence, and transparent vowels. A study of…

  2. Keynote Address: Rev. Mark Massa

    ERIC Educational Resources Information Center

    Massa, Mark S.

    2011-01-01

    Rev. Mark S. Massa, S.J., is the dean and professor of Church history at the School of Theology and Ministry at Boston College. He was invited to give a keynote to begin the third Catholic Higher Education Collaborative Conference (CHEC), cosponsored by Boston College and Fordham University. Fr. Massa's address posed critical questions about…

  3. State of the Lab Address

    ScienceCinema

    King, Alex

    2016-07-12

    In his third-annual State of the Lab address, Ames Laboratory Director Alex King called the past year one of "quiet but strong progress" and called for Ames Laboratory to continue to build on its strengths while responding to changing expectations for energy research.

  4. Research strategies for addressing uncertainties

    USGS Publications Warehouse

    Busch, David E.; Brekke, Levi D.; Averyt, Kristen; Jardine, Angela; Welling, Leigh; Garfin, Gregg; Jardine, Angela; Merideth, Robert; Black, Mary; LeRoy, Sarah

    2013-01-01

    Research Strategies for Addressing Uncertainties builds on descriptions of research needs presented elsewhere in the book; describes current research efforts and the challenges and opportunities to reduce the uncertainties of climate change; explores ways to improve the understanding of changes in climate and hydrology; and emphasizes the use of research to inform decision making.

  5. Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies.

    PubMed

    Sabatino, Marianna; Hu, Jinhui; Sommariva, Michele; Gautam, Sanjivan; Fellowes, Vicki; Hocker, James D; Dougherty, Sean; Qin, Haiying; Klebanoff, Christopher A; Fry, Terry J; Gress, Ronald E; Kochenderfer, James N; Stroncek, David F; Ji, Yun; Gattinoni, Luca

    2016-07-28

    Long-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T-cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical-grade tumor-redirected TSCM starting from naive precursors. CD8(+)CD62L(+)CD45RA(+) naive T cells enriched by streptamer-based serial-positive selection were activated by CD3/CD28 engagement in the presence of interleukin-7 (IL-7), IL-21, and the glycogen synthase-3β inhibitor TWS119, and genetically engineered to express a CD19-specific chimeric antigen receptor (CD19-CAR). These conditions enabled the generation of CD19-CAR-modified CD8(+) TSCM that were phenotypically, functionally, and transcriptomically equivalent to their naturally occurring counterpart. Compared with CD8(+) T cells generated with clinical protocols currently under investigation, CD19-CAR-modified CD8(+) TSCM exhibited enhanced metabolic fitness and mediated robust, long-lasting antitumor responses against systemic acute lymphoblastic leukemia xenografts. This clinical-grade platform provides the basis for a phase 1 trial evaluating the activity of CD19-CAR-modified CD8(+) TSCM in patients with B-cell malignancies refractory to prior allogeneic hematopoietic stem cell transplantation.

  6. Production, characterization, and application of monoclonal antibodies specific to recombinant (E2) structural protein in antigen-capture ELISA for clinical diagnosis of Chikungunya virus.

    PubMed

    Kumar, Jyoti S; Khan, Mohsin; Gupta, Garima; Bhoopati, Manna; Lakshmana Rao, P V; Parida, Manmohan

    2012-04-01

    The resurgence of Chikungunya (CHIK) virus in the form of an explosive, unprecedented epidemic with high virulence and unusual numbers of fatalities has created an immense public health concern in recent years. In the absence of an effective vaccine and specific antiviral therapy, early accurate diagnosis is essential for the best patient management. The present study describes the production and characterization of high-affinity and selective monoclonal antibodies (Mabs) against recombinant E2 protein (rE2) of the CHIK virus. The reactivity of Mabs for rE2 protein was demonstrated using ELISA. The specificity of the generated Mabs for rE2 was demonstrated by Western blot and indirect immunofluorescence. The application of this CHIK virus E2-specific monoclonal antibody in early clinical diagnosis was demonstrated by various analytical methods, such as immunoblotting, indirect immunofluorescence assay (IFA), and antigen-capture ELISA (AC-ELISA), for the detection as well as the identification of the novel ECSA genotypes of CHIK virus. These findings suggest that the high-affinity E2-specific monoclonal antibodies reported in this study will be useful for early clinical diagnosis and epidemiological studies of CHIK virus in developing countries.

  7. Matching Alternative Addresses: a Semantic Web Approach

    NASA Astrophysics Data System (ADS)

    Ariannamazi, S.; Karimipour, F.; Hakimpour, F.

    2015-12-01

    Rapid development of crowd-sourcing or volunteered geographic information (VGI) provides opportunities for authoritatives that deal with geospatial information. Heterogeneity of multiple data sources and inconsistency of data types is a key characteristics of VGI datasets. The expansion of cities resulted in the growing number of POIs in the OpenStreetMap, a well-known VGI source, which causes the datasets to outdate in short periods of time. These changes made to spatial and aspatial attributes of features such as names and addresses might cause confusion or ambiguity in the processes that require feature's literal information like addressing and geocoding. VGI sources neither will conform specific vocabularies nor will remain in a specific schema for a long period of time. As a result, the integration of VGI sources is crucial and inevitable in order to avoid duplication and the waste of resources. Information integration can be used to match features and qualify different annotation alternatives for disambiguation. This study enhances the search capabilities of geospatial tools with applications able to understand user terminology to pursuit an efficient way for finding desired results. Semantic web is a capable tool for developing technologies that deal with lexical and numerical calculations and estimations. There are a vast amount of literal-spatial data representing the capability of linguistic information in knowledge modeling, but these resources need to be harmonized based on Semantic Web standards. The process of making addresses homogenous generates a helpful tool based on spatial data integration and lexical annotation matching and disambiguating.

  8. Predictive value of specific IgE for clinical peanut allergy in children: relationship with eczema, asthma, and setting (primary or secondary care).

    PubMed

    van Veen, Wilma J; Dikkeschei, Lambert D; Roberts, Graham; Brand, Paul Lp

    2013-10-10

    The usefulness of peanut specific IgE levels for diagnosing peanut allergy has not been studied in primary and secondary care where most cases of suspected peanut allergy are being evaluated. We aimed to determine the relationship between peanut-specific IgE levels and clinical peanut allergy in peanut-sensitized children and how this was influenced by eczema, asthma and clinical setting (primary or secondary care). We enrolled 280 children (0-18 years) who tested positive for peanut-specific IgE (> 0.35 kU/L) requested by primary and secondary physicians. We used predefined criteria to classify participants into three groups: peanut allergy, no peanut allergy, or possible peanut allergy, based on responses to a validated questionnaire, a detailed food history, and results of oral food challenges.Fifty-two participants (18.6%) were classified as peanut allergy, 190 (67.9%) as no peanut allergy, and 38 (13.6%) as possible peanut allergy. The association between peanut-specific IgE levels and peanut allergy was significant but weak (OR 1.46 for a 10.0 kU/L increase in peanut-specific IgE, 95% CI 1.28-1.67). Eczema was the strongest risk factor for peanut allergy (aOR 3.33, 95% CI 1.07-10.35), adjusted for demographic and clinical characteristics. Asthma was not significantly related to peanut allergy (aOR 1.93, 95% CI 0.90-4.13). Peanut allergy was less likely in primary than in secondary care participants (OR 0.46, 95% CI 0.25-0.86), at all levels of peanut-specific IgE.The relationship between peanut-specific IgE and peanut allergy in children is weak, is strongly dependent on eczema, and is weaker in primary compared to secondary care. This limits the usefulness of peanut-specific IgE levels in the diagnosis of peanut allergy in children.

  9. Portfolios: possibilities for addressing emergency medicine resident competencies.

    PubMed

    O'Sullivan, Patricia; Greene, Constance

    2002-11-01

    Portfolios are an innovative approach to evaluate the competency of emergency medicine residents. Three key characteristics add to their attractiveness. First, portfolios draw from the resident's actual work. Second, they require self-reflection on the part of the resident. Third, they are inherently practice-based learning since residents must review and consider their practice in order to begin the portfolio. This paper illustrates five different applications of portfolios. First, portfolios are applied to evaluating specific competencies as part of the training of emergency physicians. While evaluating specific competencies, the portfolio captures aspects of the general competencies. Second, the article illustrates using portfolios as a way to address a specific residency review committee (RRC) requirement such as follow-ups. Third is a description of how portfolios can be used to evaluate resident conferences capturing the competency of practice-based learning and possibly other competencies such as medical knowledge and patient care. Fourth, the authors of the article designed a portfolio as a way to demonstrate clinical competence. Fifth, they elaborate as to how a continuous quality improvement project could be cast within the portfolio framework. They provide some guidance concerning issues to address when designing the portfolios. Portfolios are carefully structured and not haphazard collections of materials. Following criteria is important in maintaining the validity of the portfolio as well as contributing to reliability. The portfolios can enhance the relationship between faculty and residents since faculty will suggest cases, discuss anomalies, and interact with the residents around the portfolio. The authors believe that in general portfolios can cover many of the general competencies specified by the ACGME while still focusing on issues important to emergency medicine. The authors believe that portfolios provide an approach to evaluation commensurate

  10. Clinical specificity of acute versus chronic self-injury: measurement and evaluation of repetitive non-suicidal self-injury.

    PubMed

    Manca, Maura; Presaghi, Fabio; Cerutti, Rita

    2014-01-30

    Overall, previous studies on the prevalence of non-suicidal self-injury (NSSI) behaviors in the general population have stressed the importance of differentiating between occasional and repetitive NSSI, examining different severity levels (e.g., frequency and variety of methods), as well as investigating the diverse psychopathological correlates of NSSI. However, existing NSSI measures have not been explicitly developed by to comply with the NSSI diagnostic criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The purpose of this study is to develop a measure of repetitive NSSI by considering its essential features, as described in the proposed DSM-5 as well as in other clinically relevant aspects emerging from case reports. Two independent samples of participants (N1=383 young adults and 251 adolescents; N2=953 adolescents) belonging to the general population were involved in the present study. The questionnaire showed satisfactory fit statistics and reliably discriminated between occasional and repetitive self-injurers (Area Under Curve, AUC=0.755). The pattern of correlations with psychopathological measures confirmed a more clinically-compromised profile for repetitive rather than occasional self-injurers.

  11. Clinical Subtypes of Depression Are Associated with Specific Metabolic Parameters and Circadian Endocrine Profiles in Women: The Power Study

    PubMed Central

    Cizza, Giovanni; Ronsaville, Donna S.; Kleitz, Hayley; Eskandari, Farideh; Mistry, Sejal; Torvik, Sara; Sonbolian, Nina; Reynolds, James C.; Blackman, Marc R.; Gold, Philip W.; Martinez, Pedro E.

    2012-01-01

    Background Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Methods Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Results Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Conclusions Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences. Trial Registration ClinicalTrials.gov NCT00006180 PMID:22235252

  12. Handling clinical comorbidity in randomized clinical trials in psychiatry.

    PubMed

    O'Hara, Ruth; Beaudreau, Sherry A; Gould, Christine E; Froehlich, Wendy; Kraemer, Helena C

    2017-03-01

    The purpose of this paper is to a) outline the importance of including patients with clinical comorbidities in Randomized Clinical Trials (RCTs) of psychiatric treatments; and b) to propose a specific approach for best handling, analyzing and interpreting the data on clinical comorbidities in terms of their impact on treatment outcomes. To do this we first define and describe clinical comorbidity and differentiate it from other forms of comorbidity. We then describe the methodological and analytical problems associated with excluding patients with clinically comorbid conditions from RCTs, including the impact on the outcomes of RCTs in psychiatry and the impact on evidence-based clinical decision-making. We then address the challenges inherent to including patients with clinical comorbidities in RCTs. Finally, we propose a methodological and analytic approach to deal with these issues in RCTs which aims to significantly improve the information yielded from RCTs in psychiatry, and thus improve clinical decision-making.

  13. An analytical approach to corneal mechanics for determining practical, clinically-meaningful patient-specific tissue mechanical properties in the rehabilitation of vision.

    PubMed

    Asher, Roy; Gefen, Amit; Moisseiev, Elad; Varssano, David

    2015-02-01

    Patient-specific biomechanical properties of the human cornea are rarely used with finite elements analysis. In order for that to be possible, a proper formulation for biomechanical properties that is based on patient-specific measurable values must be used. In this study, we propose a formula that simulates hyperelastic stress-strain curves based on non-invasive clinical measurements that can be acquired in vivo. These consist of, but are not limited to, center corneal thickness and center corneal curvature as well as corneal resistance factor and applanation diameter that are measured during non-contact tonometry. The presented formulation was demonstrated and validated through several computer simulations. First, mean values that were reported in literature were inputted into the formula to simulate a curve that represents a healthy case. This case was compared to two independent in vitro studies. Then, a sensitivity analysis was carried to identify inputs that have the most dominant effect. Finally, a finite element analysis simulating elevations in intraocular pressure was conducted; the corneal model comprised of patient-specific corneal geometry that was measured in vivo in our clinic as well as the current formulation for patient-specific corneal biomechanics. "Strong" and "weak" corneal tissue cases were simulated and deformations as well as instantaneous curvature optical maps were derived. Results for the simulated healthy curve showed good agreement with the in vitro studies. The sensitivity analysis found the corneal resistance factor and applanation diameter to have the most dominant influence. The finite element analysis of strong and weak biomechanical properties resulted in corneal deformations and instantaneous curvature optical maps that are common for healthy and pathological conditions respectively. In conclusion, the presented modeling technique can be used to assess corneal biomechanics in vivo and therefor may enhance follow-up on the

  14. Release of palladium from biomechanical prostheses in body fluids can induce or support PD-specific IFNgamma T cell responses and the clinical setting of a palladium hypersensitivity.

    PubMed

    Cristaudo, A; Bordignon, V; Petrucci, F; Caimi, S; De Rocco, M; Picardo, M; Cordiali Fei, P; Ensoli, F

    2009-01-01

    The increased use of Palladium (Pd) for biomedical applications, which has more than doubled in the last ten years, appears to be associated with an increased frequency of adverse reactions to Pd. The aim of this study is to investigate the relationship between the implant of a biomechanical apparatus containing Pd and the setting of a hypersensitivity to Pd by determining the levels of the metal released in biological fluids, assessing the effects of Pd on peripheral blood mononuclear cell (PBMC) cytokine production and exploring the clinical setting of skin sensitization. Of a total of 3,093 subjects examined in 2006, sensitization to Pd alone or in association with nickel (Ni) was observed in 1.6% and 13.03% of the individuals, respectively. Of these, a group of six subjects positive to Pd and negative to Ni at patch testing were selected on the basis of the oral clinical symptoms in order to measure both the levels of Pd in biological fluids and the degradation of the dental prostheses. Specific Pd measurements were carried out on salivary fluid, urine and serum samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry. In addition, the degradation of the dental prostheses was assessed by both a leaching test and an analysis of the micro morphology of orthodontic prostheses. The induction of IFN-gamma production by Pd was assessed in PBMC by the ELISpot assay. Skin sensitization to Pd was evaluated by patch testing and clinical examination. Ten healthy subjects were comparatively tested as controls. We found a specific induction of an IFN-gamma response by Pd in PBMC collected from all the subjects positive to Pd at patch testing. On the contrary, control subjects did not show any response to Pd as assessed by IFN-gamma ELISpot assay or by skin testing. Remarkably, the levels of Pd in all biological samples (saliva, sera, urine) were significantly higher in Pd-sensitized patients than in those collected from controls, reaching the highest

  15. Atomic clusters with addressable complexity

    NASA Astrophysics Data System (ADS)

    Wales, David J.

    2017-02-01

    A general formulation for constructing addressable atomic clusters is introduced, based on one or more reference structures. By modifying the well depths in a given interatomic potential in favour of nearest-neighbour interactions that are defined in the reference(s), the potential energy landscape can be biased to make a particular permutational isomer the global minimum. The magnitude of the bias changes the resulting potential energy landscape systematically, providing a framework to produce clusters that should self-organise efficiently into the target structure. These features are illustrated for small systems, where all the relevant local minima and transition states can be identified, and for the low-energy regions of the landscape for larger clusters. For a 55-particle cluster, it is possible to design a target structure from a transition state of the original potential and to retain this structure in a doubly addressable landscape. Disconnectivity graphs based on local minima that have no direct connections to a lower minimum provide a helpful way to visualise the larger databases. These minima correspond to the termini of monotonic sequences, which always proceed downhill in terms of potential energy, and we identify them as a class of biminimum. Multiple copies of the target cluster are treated by adding a repulsive term between particles with the same address to maintain distinguishable targets upon aggregation. By tuning the magnitude of this term, it is possible to create assemblies of the target cluster corresponding to a variety of structures, including rings and chains.

  16. Long-acting stimulants for treatment of attention-deficit/hyperactivity disorder: a focus on extended-release formulations and the prodrug lisdexamfetamine dimesylate to address continuing clinical challenges.

    PubMed

    López, Frank A; Leroux, Jacques R

    2013-09-01

    Individuals with attention-deficit/hyperactivity disorder (ADHD) show pervasive impairments across family, peer, and school or work functioning that may extend throughout the day. Psychostimulants are highly effective medications for the treatment of ADHD, and the development of long-acting stimulant formulations has greatly expanded the treatment options for individuals with ADHD. Strategies for the formulation of long-acting stimulants include the combination of immediate-release and delayed-release beads, and an osmotic-release oral system. A recent development is the availability of the first prodrug stimulant, lisdexamfetamine dimesylate (LDX). LDX itself is inactive but is cleaved enzymatically, primarily in the bloodstream, to release d-amphetamine (d-AMP). Several clinical trials have demonstrated that long-acting stimulants are effective in reducing ADHD symptoms compared with placebo. Analog classroom and simulated adult workplace environment studies have shown that long-acting stimulants produce symptom reduction for at least 12 h. Long-acting stimulants exhibit similar tolerability and safety profiles to short-acting equivalents. While variations in gastric pH and motility can alter the availability and absorption of stimulants released from long-acting formulations, the systemic exposure to d-AMP following LDX administration is unlikely to be affected by gastrointestinal conditions. Long-acting formulations may also improve adherence and lower abuse potential compared with their short-acting counterparts. The development of long-acting stimulants provides physicians with an increased range of medication options to help tailor treatment for individuals with ADHD.

  17. The (Im)possibility of the Project: Radford Address

    ERIC Educational Resources Information Center

    Green, Bill

    2010-01-01

    In this address, the author engages both with the possibility "and" the impossibility of the educational project--and suggests something of what it means to say this. His presentation is specifically addressed to the theme of the (im)possibility of the educational project. He draws from philosophy, literature, psychoanalysis and history,…

  18. Medical-Legal Partnerships: Addressing Competency Needs Through Lawyers

    PubMed Central

    Paul, Edward; Fullerton, Danya Fortess; Cohen, Ellen; Lawton, Ellen; Ryan, Anne; Sandel, Megan

    2009-01-01

    Background Many low- and moderate-income individuals and families have at least one unmet legal need (for example, unsafe housing conditions, lack of access to food and/or income support, lack of access to health care), which, if left unaddressed, can have harmful consequences on health. Eighty unique medical-legal partnership programs, serving over 180 clinics and hospitals nationwide, seek to combine the strengths of medical and legal professionals to address patients' legal needs before they become crises. Each partnership is adapted to serve the specific needs of its own patient base. Intervention This article describes innovative, residency-based medical-legal partnership educational experiences in pediatrics, internal medicine, and family medicine at 3 different sites (Boston, Massachusetts; Newark, New Jersey; and Tucson, Arizona). This article addresses how these 3 programs have been designed to meet the Accreditation Council for Graduate Medical Education's 6 competencies, along with suggested methods for evaluating the effectiveness of these programs. Training is a core component of medical-legal partnership, and most medical-legal partnerships have developed curricula for resident education in a variety of formats, including noon conferences, grand rounds, poverty simulations and day-long special sessions. Discussion Medical-legal partnerships combine the skill sets of medical professionals and lawyers to teach social determinants of health by training residents and attending physicians to identify and help address unmet legal needs. Medical-legal partnership doctors and lawyers treat health disparities and improve patient health and well-being by ensuring that public programs, regulations, and laws created to benefit health and improve access to health care are implemented and enforced. PMID:21975996

  19. Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience

    NASA Astrophysics Data System (ADS)

    Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Jörgen; Nyholm, Tufve; Ahnesjö, Anders; Karlsson, Mikael

    2007-08-01

    Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm3 ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 ± 1.2% and 0.5 ± 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 ± 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach

  20. The neurologic control of arousal and orgasm with specific attention to spinal cord lesions: Integrating preclinical and clinical sciences.

    PubMed

    Alexander, Marcalee Sipski; Marson, Lesley

    2017-01-25

    Preclinical research in animal models is important for understanding the neural pathways and pathophysiology underlying changes in sexual function after SCI. In vivo animal models, primarily rodents, have provided valuable information on the central pathways regulating sexual arousal and orgasm; however, further research is required in females and preclinical modeling of SCI that can be better translated to men and women. Translation of the autonomic and somatic regulation of sexual responses from preclinical models through clinical research correlates well with respect to the peripheral-spinal systems involved. However, due to the nature of sexual responses, parallel studies are necessary in animals and humans. Human studies of individuals with SCIs have provided information about the neurologic control of arousal and orgasm. Psychogenic arousal is related to the preservation of sensation at T11-L2 whereas orgasm requires the presence of an intact sacral reflex arc. Studies point to evidence of a spinal pattern generator at L3-5. Because of the exact nature of SCIs, further research using neuroimaging will be beneficial, not only to elucidate the neurological control of sexual responses after SCI, but also in able-bodied individuals. Understanding and ameliorating the effects of SCI on sexual function is important to the well-being and quality of life of individuals with SCIs and their partners, thus future research should focus more on this important topic.

  1. Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application

    PubMed Central

    Koppaka, Vindhya; Thompson, David C.; Chen, Ying; Ellermann, Manuel; Nicolaou, Kyriacos C.; Juvonen, Risto O.; Petersen, Dennis; Deitrich, Richard A.; Hurley, Thomas D.

    2012-01-01

    Aldehyde dehydrogenases (ALDHs) belong to a superfamily of enzymes that play a key role in the metabolism of aldehydes of both endogenous and exogenous derivation. The human ALDH superfamily comprises 19 isozymes that possess important physiological and toxicological functions. The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Many ALDH isozymes are important in oxidizing reactive aldehydes derived from lipid peroxidation and thereby help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes have been reported in various human cancers and are associated with cancer relapse. As a direct consequence of their significant physiological and toxicological roles, inhibitors of the ALDH enzymes have been developed to treat human diseases. This review summarizes known ALDH inhibitors, their mechanisms of action, isozyme selectivity, potency, and clinical uses. The purpose of this review is to 1) establish the current status of pharmacological inhibition of the ALDHs, 2) provide a rationale for the continued development of ALDH isozyme-selective inhibitors, and 3) identify the challenges and potential therapeutic rewards associated with the creation of such agents. PMID:22544865

  2. Origins of task-specific sensory-independent organization in the visual and auditory brain: neuroscience evidence, open questions and clinical implications.

    PubMed

    Heimler, Benedetta; Striem-Amit, Ella; Amedi, Amir

    2015-12-01

    Evidence of task-specific sensory-independent (TSSI) plasticity from blind and deaf populations has led to a better understanding of brain organization. However, the principles determining the origins of this plasticity remain unclear. We review recent data suggesting that a combination of the connectivity bias and sensitivity to task-distinctive features might account for TSSI plasticity in the sensory cortices as a whole, from the higher-order occipital/temporal cortices to the primary sensory cortices. We discuss current theories and evidence, open questions and related predictions. Finally, given the rapid progress in visual and auditory restoration techniques, we address the crucial need to develop effective rehabilitation approaches for sensory recovery.

  3. Current progress in patient-specific modeling

    PubMed Central

    2010-01-01

    We present a survey of recent advancements in the emerging field of patient-specific modeling (PSM). Researchers in this field are currently simulating a wide variety of tissue and organ dynamics to address challenges in various clinical domains. The majority of this research employs three-dimensional, image-based modeling techniques. Recent PSM publications mostly represent feasibility or preliminary validation studies on modeling technologies, and these systems will require further clinical validation and usability testing before they can become a standard of care. We anticipate that with further testing and research, PSM-derived technologies will eventually become valuable, versatile clinical tools. PMID:19955236

  4. Clinically defined non-specific symptoms in the vicinity of mobile phone base stations: A retrospective before-after study.

    PubMed

    Baliatsas, Christos; van Kamp, Irene; Bolte, John; Kelfkens, Gert; van Dijk, Christel; Spreeuwenberg, Peter; Hooiveld, Mariette; Lebret, Erik; Yzermans, Joris

    2016-09-15

    The number of mobile phone base station(s) (MPBS) has been increasing to meet the rapid technological changes and growing needs for mobile communication. The primary objective of the present study was to test possible changes in prevalence and number of NSS in relation to MPBS exposure before and after increase of installed MPBS antennas. A retrospective cohort study was conducted, comparing two time periods with high contrast in terms of number of installed MPBS. Symptom data were based on electronic health records from 1069 adult participants, registered in 9 general practices in different regions in the Netherlands. All participants were living within 500m from the nearest bases station. Among them, 55 participants reported to be sensitive to MPBS at T1. A propagation model combined with a questionnaire was used to assess indoor exposure to RF-EMF from MPBS at T1. Estimation of exposure at T0 was based on number of antennas at T0 relative to T1. At T1, there was a >30% increase in the total number of MPBS antennas. A higher prevalence for most NSS was observed in the MPBS-sensitive group at T1 compared to baseline. Exposure estimates were not associated with GP-registered NSS in the total sample. Some significant interactions were observed between MPBS-sensitivity and exposure estimates on risk of symptoms. Using clinically defined outcomes and a time difference of >6years it was demonstrated that RF-EMF exposure to MPBS was not associated with the development of NSS. Nonetheless, there was some indication for a higher risk of NSS for the MPBS-sensitive group, mainly in relation to exposure to UMTS, but this should be interpreted with caution. Results have to be verified by future longitudinal studies with a particular focus on potentially susceptible population subgroups of large sample size and integrated exposure assessment.

  5. Optimization of a Class of Tryptophan Dendrimers That Inhibit HIV Replication Leads to a Selective, Specific, and Low-Nanomolar Inhibitor of Clinical Isolates of Enterovirus A71

    PubMed Central

    Rivero-Buceta, Eva; Sun, Liang; Martínez-Gualda, Belén; Doyagüez, Elisa G.; Donckers, Kim; Quesada, Ernesto; Camarasa, María-José; Delang, Leen; Leyssen, Pieter

    2016-01-01

    Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range. PMID:27246775

  6. Identifying and Addressing Vaccine Hesitancy

    PubMed Central

    Kestenbaum, Lori A.; Feemster, Kristen A.

    2015-01-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as vaccine hesitant. This phenomenon has developed due to the confluence of multiple social, cultural, political and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance. PMID:25875982

  7. Identifying and addressing vaccine hesitancy.

    PubMed

    Kestenbaum, Lori A; Feemster, Kristen A

    2015-04-01

    In the 20th century, the introduction of multiple vaccines significantly reduced childhood morbidity, mortality, and disease outbreaks. Despite, and perhaps because of, their public health impact, an increasing number of parents and patients are choosing to delay or refuse vaccines. These individuals are described as "vaccine hesitant." This phenomenon has developed due to the confluence of multiple social, cultural, political, and personal factors. As immunization programs continue to expand, understanding and addressing vaccine hesitancy will be crucial to their successful implementation. This review explores the history of vaccine hesitancy, its causes, and suggested approaches for reducing hesitancy and strengthening vaccine acceptance.

  8. Nanoscale content-addressable memory

    NASA Technical Reports Server (NTRS)

    Davis, Bryan (Inventor); Principe, Jose C. (Inventor); Fortes, Jose (Inventor)

    2009-01-01

    A combined content addressable memory device and memory interface is provided. The combined device and interface includes one or more one molecular wire crossbar memories having spaced-apart key nanowires, spaced-apart value nanowires adjacent to the key nanowires, and configurable switches between the key nanowires and the value nanowires. The combination further includes a key microwire-nanowire grid (key MNG) electrically connected to the spaced-apart key nanowires, and a value microwire-nanowire grid (value MNG) electrically connected to the spaced-apart value nanowires. A key or value MNGs selects multiple nanowires for a given key or value.

  9. Addressing inequities in healthy eating.

    PubMed

    Friel, Sharon; Hattersley, Libby; Ford, Laura; O'Rourke, Kerryn

    2015-09-01

    What, when, where and how much people eat is influenced by a complex mix of factors at societal, community and individual levels. These influences operate both directly through the food system and indirectly through political, economic, social and cultural pathways that cause social stratification and influence the quality of conditions in which people live their lives. These factors are the social determinants of inequities in healthy eating. This paper provides an overview of the current evidence base for addressing these determinants and for the promotion of equity in healthy eating.

  10. Addressing the workforce pipeline challenge

    SciTech Connect

    Leonard Bond; Kevin Kostelnik; Richard Holman

    2006-11-01

    A secure and affordable energy supply is essential for achieving U.S. national security, in continuing U.S. prosperity and in laying the foundations to enable future economic growth. To meet this goal the next generation energy workforce in the U.S., in particular those needed to support instrumentation, controls and advanced operations and maintenance, is a critical element. The workforce is aging and a new workforce pipeline, to support both current generation and new build has yet to be established. The paper reviews the challenges and some actions being taken to address this need.

  11. Innovative Legal Approaches to Address Obesity

    PubMed Central

    Pomeranz, Jennifer L; Teret, Stephen P; Sugarman, Stephen D; Rutkow, Lainie; Brownell, Kelly D

    2009-01-01

    Context: The law is a powerful public health tool with considerable potential to address the obesity issue. Scientific advances, gaps in the current regulatory environment, and new ways of conceptualizing rights and responsibilities offer a foundation for legal innovation. Methods: This article connects developments in public health and nutrition with legal advances to define promising avenues for preventing obesity through the application of the law. Findings: Two sets of approaches are defined: (1) direct application of the law to factors known to contribute to obesity and (2) original and innovative legal solutions that address the weak regulatory stance of government and the ineffectiveness of existing policies used to control obesity. Specific legal strategies are discussed for limiting children's food marketing, confronting the potential addictive properties of food, compelling industry speech, increasing government speech, regulating conduct, using tort litigation, applying nuisance law as a litigation strategy, and considering performance-based regulation as an alternative to typical regulatory actions. Finally, preemption is an overriding issue and can play both a facilitative and a hindering role in obesity policy. Conclusions: Legal solutions are immediately available to the government to address obesity and should be considered at the federal, state, and local levels. New and innovative legal solutions represent opportunities to take the law in creative directions and to link legal, nutrition, and public health communities in constructive ways. PMID:19298420

  12. Global-Address Space Networking (GASNet) Library

    SciTech Connect

    Welcome, Michael L.; Bell, Christian S.

    2011-04-06

    GASNet (Global-Address Space Networking) is a language-independent, low-level networking layer that provides network-independent, high-performance communication primitives tailored for implementing parallel global address space SPMD languages such as UPC and Titanium. The interface is primarily intended as a compilation target and for use by runtime library writers (as opposed to end users), and the primary goals are high performance, interface portability, and expressiveness. GASNet is designed specifically to support high-performance, portable implementations of global address space languages on modern high-end communication networks. The interface provides the flexibility and extensibility required to express a wide variety of communication patterns without sacrificing performance by imposing large computational overheads in the interface. The design of the GASNet interface is partitioned into two layers to maximize porting ease without sacrificing performance: the lower level is a narrow but very general interface called the GASNet core API - the design is basedheavily on Active Messages, and is implemented directly on top of each individual network architecture. The upper level is a wider and more expressive interface called GASNet extended API, which provides high-level operations such as remote memory access and various collective operations. This release implements GASNet over MPI, the Quadrics "elan" API, the Myrinet "GM" API and the "LAPI" interface to the IBM SP switch. A template is provided for adding support for additional network interfaces.

  13. The effect of aneurismal-wall mechanical properties on patient-specific hemodynamic simulations: two clinical case reports

    NASA Astrophysics Data System (ADS)

    Chen, Jialiang; Wang, Shengzhang; Ding, Guanghong; Yang, Xinjian; Li, Haiyun

    2009-10-01

    Hemodynamic factors such as the wall shear stress play an important role in the pathogenesis and treatment of cerebral aneurysms. In present study, we apply computational fluid-structure interaction analyses on cerebral aneurysms with two different constitutive relations for aneurismal wall in order to investigate the effect of the aneurismal wall mechanical properties on the simulation results. We carry out these analyses by using two patient-specific models of cerebral aneurysms of different sizes located in different branches of the circle of Willis. The models are constructed from 3D rotational angiography image data and blood flow dynamics is studied under physiologically representative waveform of inflow. From the patient models analyzed in this investigation, we find that the deformations of cerebral aneurysms are very small. But due to the nonlinear character of the Navier-Stokes equations, these small deformations could have significant influences on the flow characteristics. In addition, we find that the aneurismal-wall mechanical properties have great effects on the deformation distribution of the aneurysm, which also affects the wall shear stress distribution and flow patterns. Therefore, how to define a proper constitutive relation for aneurismal wall should be considered carefully in the hemodynamic simulation.

  14. Desensitization for renal transplantation: depletion of donor-specific anti-HLA antibodies, preservation of memory antibodies, and clinical risks.

    PubMed

    Rogers, Natasha M; Eng, Hooi S; Yu, Raymond; Kireta, Svjetlana; Tsiopelas, Eleni; Bennett, Greg D; Brook, Nicholas R; Gillis, David; Russ, Graeme R; Coates, P Toby

    2011-01-01

    Desensitization protocols reduce donor-specific anti-HLA antibodies (DSA) and enable renal transplantation in patients with a positive complement-dependent cytotoxic cross-match (CDC-CXM). The effect of this treatment on protective antibody and immunoglobulin levels is unknown. Thirteen patients with end-stage renal disease, DSA and positive CDC-CXM underwent desensitization. Sera collected pre- and post-transplantation were analysed for anti-tetanus and anti-pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and were compared to healthy controls and contemporaneous renal transplant recipients treated with standard immunosuppression alone. Ten patients developed negative CDC-CXM and enzyme-linked immunosorbent assay (ELISA) and underwent successful transplantation. Eight recipients achieved good graft function without antibody-mediated or late rejection, BK virus or cytomegalovirus infection. One patient had primary non-function due to recurrent oxalosis, and one patient with immediate graft function died from septicaemia. Seven recipients required post-operative transfusion and three developed septicaemia. DSA remained negative by ELISA at 12 months, but were detectable by Luminex(®) . Anti-tetanus and anti-pneumococcal antibodies, total Ig and IgG subclasses were below the normal range but comparable to levels in renal transplant recipients who had not undergone desensitization. Desensitization protocols effectively reduce DSA and allow successful transplantation. Post-operative bleeding and short-term infectious risk is increased. Protective antibody and serum immunoglobulin levels are relatively preserved.

  15. Clinical Study of 3D Imaging and 3D Printing Technique for Patient-Specific Instrumentation in Total Knee Arthroplasty.

    PubMed

    Qiu, Bing; Liu, Fei; Tang, Bensen; Deng, Biyong; Liu, Fang; Zhu, Weimin; Zhen, Dong; Xue, Mingyuan; Zhang, Mingjiao

    2017-01-25

    Patient-specific instrumentation (PSI) was designed to improve the accuracy of preoperative planning and postoperative prosthesis positioning in total knee arthroplasty (TKA). However, better understanding needs to be achieved due to the subtle nature of the PSI systems. In this study, 3D printing technique based on the image data of computed tomography (CT) has been utilized for optimal controlling of the surgical parameters. Two groups of TKA cases have been randomly selected as PSI group and control group with no significant difference of age and sex (p > 0.05). The PSI group is treated with 3D printed cutting guides whereas the control group is treated with conventional instrumentation (CI). By evaluating the proximal osteotomy amount, distal osteotomy amount, valgus angle, external rotation angle, and tibial posterior slope angle of patients, it can be found that the preoperative quantitative assessment and intraoperative changes can be controlled with PSI whereas CI is relied on experience. In terms of postoperative parameters, such as hip-knee-ankle (HKA), frontal femoral component (FFC), frontal tibial component (FTC), and lateral tibial component (LTC) angles, there is a significant improvement in achieving the desired implant position (p < 0.05). Assigned from the morphology of patients' knees, the PSI represents the convergence of congruent designs with current personalized treatment tools. The PSI can achieve less extremity alignment and greater accuracy of prosthesis implantation compared against control method, which indicates potential for optimal HKA, FFC, and FTC angles.

  16. One-session treatment of specific phobias in youth: a randomized clinical trial in the United States and Sweden.

    PubMed

    Ollendick, Thomas H; Ost, Lars-Göran; Reuterskiöld, Lena; Costa, Natalie; Cederlund, Rio; Sirbu, Cristian; Davis, Thompson E; Jarrett, Matthew A

    2009-06-01

    One hundred and ninety-six youth, ages 7-16, who fulfilled Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for various specific phobias were randomized to a one-session exposure treatment, education support treatment, or a wait list control group. After the waiting period, the wait list participants were offered treatment and, if interested, rerandomized to 1 of the 2 active treatments. The phobias were assessed with semistructured diagnostic interviews, clinician severity ratings, and behavioral avoidance tests, whereas fears, general anxiety, depression, and behavior problems were assessed with self- and parent report measures. Assessments were completed pretreatment, posttreatment, and at 6 months following treatment. Results showed that both treatment conditions were superior to the wait list control condition and that 1-session exposure treatment was superior to education support treatment on clinician ratings of phobic severity, percentage of participants who were diagnosis free, child ratings of anxiety during the behavioral avoidance test, and treatment satisfaction as reported by the youth and their parents. There were no differences on self-report measures. Treatment effects were maintained at follow-up. Implications of these findings are discussed.

  17. Meta-analysis of clinical data using human meiotic genes identifies a novel cohort of highly restricted cancer-specific marker genes.

    PubMed

    Feichtinger, Julia; Aldeailej, Ibrahim; Anderson, Rebecca; Almutairi, Mikhlid; Almatrafi, Ahmed; Alsiwiehri, Naif; Griffiths, Keith; Stuart, Nicholas; Wakeman, Jane A; Larcombe, Lee; McFarlane, Ramsay J

    2012-08-01

    Identifying cancer-specific biomarkers represents an ongoing challenge to the development of novel cancer diagnostic, prognostic and therapeutic strategies. Cancer/testis (CT) genes are an important gene family with expression tightly restricted to the testis in normal individuals but which can also be activated in cancers. Here we develop a pipeline to identify new CT genes. We analysed and validated expression profiles of human meiotic genes in normal and cancerous tissue followed by meta-analyses of clinical data sets from a range of tumour types resulting in the identification of a large cohort of highly specific cancer biomarker genes, including the recombination hot spot activator PRDM9 and the meiotic cohesin genes SMC1beta and RAD21L. These genes not only provide excellent cancer biomarkers for diagnostics and prognostics, but may serve as oncogenes and have excellent drug targeting potential.

  18. A Clinical Trial of Translation of Evidence Based Interventions to Mobile Tablets and Illness Specific Internet Sites

    PubMed Central

    Smith, Carol E; Piamjariyakul, Ubolrat; Werkowitch, Marilyn; Yadrich, Donna Macan; Thompson, Noreen; Hooper, Dedrick; Nelson, Eve-Lynn

    2016-01-01

    This article describes a method to translate an evidence based health care intervention to the mobile environment. This translation assisted patient participants to: avoid life threatening infections; monitor emotions and fatigue; keep involved in healthy activities. The mobile technology also decreased costs by reducing for example travel to visit health care providers. Testing of this translation method and its use by comparison groups of patients adds to the knowledge base for assessing technology for its impact on health outcome measures. The challenges and workflow of designing materials for the mobile format are described. Transitioning clinical trial verified interventions, previously provided in person to patients, onto tablet and internet platforms is an important process that must be evaluated. In this study, our evidence based guide’s intravenous (IV) homeCare interventions (IVhomeCare) were delivered via Apple iPad mini™ tablet audiovisual instruction / discussion sessions and on a website. Each iPad audiovisual session (n = 41), included three to five families, a mental health specialist, and healthcare professionals. Patients and their family caregivers readily learned to use the wireless mobile tablets, and the IVhomeCare interventions, as described here, were successfully translated onto these mobile technology platforms. Using Likert scale responses on a questionnaire (1 = not helpful and 5 = very helpful) participants indicated that they gained problem solving skills for home care through iPad group discussion (M = 4.60, SD = 0.60). The firewall protected videoconferencing in real time with multiple healthcare professionals effectively allowed health history taking and visual inspection of the patient’s IV insertion site for signs of infection. Supportive interactions with peer families on videoconferencing were documented during discussions. Discussion topics included low moods, fatigue, infection worry, how to maintain independence, and

  19. A Clinical Trial of Translation of Evidence Based Interventions to Mobile Tablets and Illness Specific Internet Sites.

    PubMed

    Smith, Carol E; Piamjariyakul, Ubolrat; Werkowitch, Marilyn; Yadrich, Donna Macan; Thompson, Noreen; Hooper, Dedrick; Nelson, Eve-Lynn

    2016-03-01

    This article describes a method to translate an evidence based health care intervention to the mobile environment. This translation assisted patient participants to: avoid life threatening infections; monitor emotions and fatigue; keep involved in healthy activities. The mobile technology also decreased costs by reducing for example travel to visit health care providers. Testing of this translation method and its use by comparison groups of patients adds to the knowledge base for assessing technology for its impact on health outcome measures. The challenges and workflow of designing materials for the mobile format are described. Transitioning clinical trial verified interventions, previously provided in person to patients, onto tablet and internet platforms is an important process that must be evaluated. In this study, our evidence based guide's intravenous (IV) homeCare interventions (IVhomeCare) were delivered via Apple iPad mini™ tablet audiovisual instruction / discussion sessions and on a website. Each iPad audiovisual session (n = 41), included three to five families, a mental health specialist, and healthcare professionals. Patients and their family caregivers readily learned to use the wireless mobile tablets, and the IVhomeCare interventions, as described here, were successfully translated onto these mobile technology platforms. Using Likert scale responses on a questionnaire (1 = not helpful and 5 = very helpful) participants indicated that they gained problem solving skills for home care through iPad group discussion (M = 4.60, SD = 0.60). The firewall protected videoconferencing in real time with multiple healthcare professionals effectively allowed health history taking and visual inspection of the patient's IV insertion site for signs of infection. Supportive interactions with peer families on videoconferencing were documented during discussions. Discussion topics included low moods, fatigue, infection worry, how to maintain independence, and need

  20. Requisite analytic and diagnostic performance characteristics for the clinical detection of BRAF V600E in hairy cell leukemia: a comparison of 2 allele-specific PCR assays.

    PubMed

    Brown, Noah A; Weigelin, Helmut C; Bailey, Nathanael; Laliberte, Julie; Elenitoba-Johnson, Kojo S J; Lim, Megan S; Betz, Bryan L

    2015-09-01

    Detection of high-frequency BRAF V600E mutations in hairy cell leukemia (HCL) has important diagnostic utility. However, the requisite analytic performance for a clinical assay to routinely detect BRAF V600E mutations in HCL has not been clearly defined. In this study, we sought to determine the level of analytic sensitivity needed for formalin-fixed, paraffin-embedded (FFPE) and frozen samples and to compare the performance of 2 allele-specific polymerase chain reaction (PCR) assays. Twenty-nine cases of classic HCL, including 22 FFPE bone marrow aspirates and 7 frozen specimens from blood or bone marrow were evaluated using a laboratory-developed allele-specific PCR assay and a commercially available allele-specific quantitative PCR assay-myT BRAF Ultra. Also included were 6 HCL variant and 40 non-HCL B-cell lymphomas. Two cases of classic HCL, 1 showing CD5 expression, were truly BRAF V600E-negative based on negative results by PCR and sequencing despite high-level leukemic involvement. Among the remaining 27 specimens, V600E mutations were detected in 88.9% (17/20 FFPE; 7/7 frozen) and 81.5% (15/20 FFPE; 7/7 frozen), for the laboratory-developed and commercial assays, respectively. No mutations were detected among the 46 non-HCL lymphomas. Both assays showed an analytic sensitivity of 0.3% involvement in frozen specimens and 5% in FFPE tissue. On the basis of these results, an assay with high analytic sensitivity is required for the clinical detection of V600E mutations in HCL specimens. Two allele-specific PCR assays performed well in both frozen and FFPE bone marrow aspirates, although detection in FFPE tissue required 5% or more involvement.

  1. Evaluation of deformation accuracy of a virtual pneumoperitoneum method based on clinical trials for patient-specific laparoscopic surgery simulator

    NASA Astrophysics Data System (ADS)

    Oda, Masahiro; Qu, Jia Di; Nimura, Yukitaka; Kitasaka, Takayuki; Misawa, Kazunari; Mori, Kensaku

    2012-02-01

    This paper evaluates deformation accuracy of a virtual pneumoperitoneum method by utilizing measurement data of real deformations of patient bodies. Laparoscopic surgery is an option of surgical operations that is less invasive technique as compared with traditional surgical operations. In laparoscopic surgery, the pneumoperitoneum process is performed to create a viewing and working space. Although a virtual pneumoperitoneum method based on 3D CT image deformation has been proposed for patient-specific laparoscopy simulators, quantitative evaluation based on measurements obtained in real surgery has not been performed. In this paper, we evaluate deformation accuracy of the virtual pneumoperitoneum method based on real deformation data of the abdominal wall measured in operating rooms (ORs.) The evaluation results are used to find optimal deformation parameters of the virtual pneumoperitoneum method. We measure landmark positions on the abdominal wall on a 3D CT image taken before performing a pneumoperitoneum process. The landmark positions are defined based on anatomical structure of a patient body. We also measure the landmark positions on a 3D CT image deformed by the virtual pneumoperitoneum method. To measure real deformations of the abdominal wall, we measure the landmark positions on the abdominal wall of a patient before and after the pneumoperitoneum process in the OR. We transform the landmark positions measured in the OR from the tracker coordinate system to the CT coordinate system. A positional error of the virtual pneumoperitoneum method is calculated based on positional differences between the landmark positions on the 3D CT image and the transformed landmark positions. Experimental results based on eight cases of surgeries showed that the minimal positional error was 13.8 mm. The positional error can be decreased from the previous method by calculating optimal deformation parameters of the virtual pneumoperitoneum method from the experimental

  2. Sex Differences in Mechanisms and Outcome of Neonatal Hypoxia-Ischemia in Rodent Models: Implications for Sex-Specific Neuroprotection in Clinical Neonatal Practice

    PubMed Central

    Hill, Courtney A.; Fitch, R. Holly

    2012-01-01

    Clinical findings show that male infants with hypoxic-ischemic injury (HI) fare more poorly than matched females on cognitive outcomes. Rodent models of neonatal hypoxia-ischemia support this difference, with data showing that perinatal brain injury leads to long-term behavioral deficits primarily in male rodents and in female rodents treated with early androgens. Results support the idea that sex-specific gonadal hormones may modulate developmental response to injury and dovetail with overwhelming evidence of developmental androgen effects on typical brain morphology and behavior. However, mechanisms underlying sex differences in response to early brain injury may be more complicated. Specifically, activation of cell death pathways in response to HI may also differ by sex. In females, the preferential activation of the caspase-dependent apoptotic pathway may actually afford greater protection, potentially due to the actions of X-linked inhibitor of apoptosis (XIAP) within this pathway. This contrasts the pattern of preferential activation of the caspase-independent pathway in males. While an integrated model of sex-specific hormonal and genetic modulation of response to early injury remains to be fully elucidated, these findings suggest that infants might benefit from sex-specific neuroprotection following HI injury. PMID:22474588

  3. Effect of Seven Sessions of Posterior-to-Anterior Spinal Mobilisation versus Prone Press-ups in Non-Specific Low Back Pain – Randomized Clinical Trial

    PubMed Central

    Kage, Vijay

    2016-01-01

    Introduction Low back pain is non-specific in 85% of population. Posterior-to-anterior (PA) mobilization and press-up exercises are common physical therapy interventions used to treat low back pain. Aim The purpose of this study was to investigate the effect of posterior-to-anterior spinal mobilization and prone press-ups in non-specific low back pain. Materials and Methods The study design was double blind randomized clinical trial. Forty participants reporting to Physiotherapy Out-patient department in hospital who were 18-45 years of age and had diagnosis of non-specific low back pain were included. Primary outcome measures were lumbar extension range, pain and physical function. Results Both interventions resulted in significant reduction in the average pain scores for both groups. Similarly, gain in total lumbar extension was significant in both the PA mobilization group and the press-up group. Functional scores significantly improved for both the groups. Both the groups significantly differed in terms of pain, lumbar extension and functional scores. PA mobilization proved to be a superior intervention. Conclusion PA mobilization and press-ups can be used as an effective intervention in non-specific low back pain. PMID:27134987

  4. Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy

    SciTech Connect

    Lee, Andrew K. . E-mail: aklee@mdanderson.org; Levy, Larry B.; Cheung, Rex; Kuban, Deborah

    2005-10-01

    Purpose: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. Methods and Materials: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. 'Any' clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. 'True' clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. Results: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) {<=}8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p 0.008) and PSADT {<=}8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical

  5. SU-E-T-798: Verification of 3DVH Dose Distribution Before Clinical Implementation for Patient-Specific IMRT QA

    SciTech Connect

    McFadden, D

    2015-06-15

    Purpose: In recent years patient-specific IMRT QA has transitioned from film and chamber measurements to beam-by-beam 2D array measurements. 3DVH takes this transition a step further by estimating the 3D dose distribution delivered using 2D per beam diode array measurements. In this study, the 3D dose distribution generated by 3DVH is compared to film and chamber measurements. In addition, the accuracy ROI volume and error detection is investigated. Methods: Composite film and ion chamber measurements in a solid water phantom were performed for 9 IMRT PINNACLE patient plans for 4 treatment sites. The film and chamber measurements were compared to the dose distribution predicted by 3DVH using MAPCHECK2 per beam measurements. The absolute point dose measurement (CAX) was extracted from the predicted 3DVH and PINNACLE dose distribution and was compared by taking the ratio of measured to predicted doses. The dose distribution measured with film was compared to the distribution in the corresponding plane (AX, SAG, COR) extracted from predicted dose distribution by 3DVH and PINNACLE using a 2D gamma analysis. Gamma analysis was performed with 2% dose, 2 mm DTA, 20% threshold, and global normalization. In addition, the percent difference between 3DVH and PINNACLE ROI volumes was calculated. Results: The average ratio of the measured point dose vs the 3DVH predicted dose was 1.017 (σ=0.011). The average gamma passing rate for measured vs 3DVH dose distributions was 95.1% (σ=2.53%). The average percent difference of 3DVH vs PINNACLE ROI volume was 2.29% (σ=2.5%). Conclusion: The dose distributions predicted by 3DVH using MAPCHECK2 measurements are the same as the distributions that would have been obtained using film and chamber. The ROI volumes used in 3DVH are not an exact match to those in PINNACLE; the effect requires more investigation. The accuracy of error detection by 3DVH is currently being investigated.

  6. The impact of AAV capsid-specific T cell responses on design and outcome of clinical gene transfer trials with recombinant AAV vectors - an evolving controversy.

    PubMed

    Ertl, Hildegund Cj; High, Katherine A

    2017-01-02

    Recombinant adenovirus-associated (rAAV) vectors due to their ease of construction, wide tissue tropism and lack of pathogenicity remain at the forefront for long-term gene replacement therapy. In spite of very encouraging pre-clinical results, clinical trials were initially unsuccessful; expression of the rAAV vector-delivered therapeutic protein was transient. Loss of expression was linked to an expansion of AAV capsid-specific T cell responses, leading to the hypothesis that rAAV vectors recall pre-existing memory T cells that had been induced by natural infections with AAV together with a helper virus. Although this was hotly debated at first, AAV capsid-specific T cell responses were observed in several gene transfer trials that used high doses of rAAV vectors. Subsequent trials designed to circumvent these T cell responses through the use of immunosuppressive drugs, rAAV vectors based on rare serotypes or modified to allow for therapeutic levels of the transgene product at low, non-immunogenic vector doses are now successful in correcting debilitating diseases.

  7. Clinical Relevance of Specific Cognitive Complaints in Determining Mild Cognitive Impairment from Cognitively Normal States in a Study of Healthy Elderly Controls.

    PubMed

    Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A

    2016-01-01

    Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.

  8. Clinical Relevance of Specific Cognitive Complaints in Determining Mild Cognitive Impairment from Cognitively Normal States in a Study of Healthy Elderly Controls

    PubMed Central

    Ávila-Villanueva, Marina; Rebollo-Vázquez, Ana; Ruiz-Sánchez de León, José M.; Valentí, Meritxell; Medina, Miguel; Fernández-Blázquez, Miguel A.

    2016-01-01

    Introduction: Subjective memory complaints (SMC) in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI) by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ). Materials and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI). The EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis (EFA) and Item Response Theory (IRT) were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI. Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely Forgetfulness of Immediate Information (FII), Executive Functions (EF) and Prospective Memory (PM) proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10). Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to use the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints. PMID:27757082

  9. Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications

    PubMed Central

    Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon

    2016-01-01

    The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors. PMID:27760181

  10. Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications.

    PubMed

    Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

    2016-01-01

    The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors.

  11. Content-addressable holographic databases

    NASA Astrophysics Data System (ADS)

    Grawert, Felix; Kobras, Sebastian; Burr, Geoffrey W.; Coufal, Hans J.; Hanssen, Holger; Riedel, Marc; Jefferson, C. Michael; Jurich, Mark C.

    2000-11-01

    Holographic data storage allows the simultaneous search of an entire database by performing multiple optical correlations between stored data pages and a search argument. We have recently developed fuzzy encoding techniques for this fast parallel search and demonstrated a holographic data storage system that searches digital data records with high fidelity. This content-addressable retrieval is based on the ability to take the two-dimensional inner product between the search page and each stored data page. We show that this ability is lost when the correlator is defocussed to avoid material oversaturation, but can be regained by the combination of a random phase mask and beam confinement through total internal reflection. Finally, we propose an architecture in which spatially multiplexed holograms are distributed along the path of the search beam, allowing parallel search of large databases.

  12. Addressing Failures in Exascale Computing

    SciTech Connect

    Snir, Marc; Wisniewski, Robert; Abraham, Jacob; Adve, Sarita; Bagchi, Saurabh; Balaji, Pavan; Belak, J.; Bose, Pradip; Cappello, Franck; Carlson, Bill; Chien, Andrew; Coteus, Paul; DeBardeleben, Nathan; Diniz, Pedro; Engelmann, Christian; Erez, Mattan; Fazzari, Saverio; Geist, Al; Gupta, Rinku; Johnson, Fred; Krishnamoorthy, Sriram; Leyffer, Sven; Liberty, Dean; Mitra, Subhasish; Munson, Todd; Schreiber, Rob; Stearley, Jon; Van Hensbergen, Eric

    2014-01-01

    We present here a report produced by a workshop on Addressing failures in exascale computing' held in Park City, Utah, 4-11 August 2012. The charter of this workshop was to establish a common taxonomy about resilience across all the levels in a computing system, discuss existing knowledge on resilience across the various hardware and software layers of an exascale system, and build on those results, examining potential solutions from both a hardware and software perspective and focusing on a combined approach. The workshop brought together participants with expertise in applications, system software, and hardware; they came from industry, government, and academia, and their interests ranged from theory to implementation. The combination allowed broad and comprehensive discussions and led to this document, which summarizes and builds on those discussions.

  13. Addressing failures in exascale computing

    SciTech Connect

    Snir, Marc; Wisniewski, Robert W.; Abraham, Jacob A.; Adve, Sarita; Bagchi, Saurabh; Balaji, Pavan; Belak, Jim; Bose, Pradip; Cappello, Franck; Carlson, William; Chien, Andrew A.; Coteus, Paul; Debardeleben, Nathan A.; Diniz, Pedro; Engelmann, Christian; Erez, Mattan; Saverio, Fazzari; Geist, Al; Gupta, Rinku; Johnson, Fred; Krishnamoorthy, Sriram; Leyffer, Sven; Liberty, Dean; Mitra, Subhasish; Munson, Todd; Schreiber, Robert; Stearly, Jon; Van Hensbergen, Eric

    2014-05-01

    We present here a report produced by a workshop on “Addressing Failures in Exascale Computing” held in Park City, Utah, August 4–11, 2012. The charter of this workshop was to establish a common taxonomy about resilience across all the levels in a computing system; discuss existing knowledge on resilience across the various hardware and software layers of an exascale system; and build on those results, examining potential solutions from both a hardware and software perspective and focusing on a combined approach. The workshop brought together participants with expertise in applications, system software, and hardware; they came from industry, government, and academia; and their interests ranged from theory to implementation. The combination allowed broad and comprehensive discussions and led to this document, which summarizes and builds on those discussions.

  14. Light addressable photoelectrochemical cyanide sensor

    SciTech Connect

    Licht, S.; Myung, N.; Sun, Y.

    1996-03-15

    A sensor is demonstrated that is capable of spatial discrimination of cyanide with use of only a single stationary sensing element. Different spatial regions of the sensing element are light activated to reveal the solution cyanide concentration only at the point of illumination. In this light addressable photoelectrochemical (LAP) sensor the sensing element consists of an n-CdSe electrode immersed in solution, with the open-circuit potential determined under illumination. In alkaline ferro-ferri-cyanide solution, the open-circuit photopotential is highly responsive to cyanide, with a linear response of (120 mV) log [KCN]. LAP detection with a spatial resolution of {+-}1 mm for cyanide detection is demonstrated. The response is almost linear for 0.001-0.100 m cyanide with a resolution of 5 mV. 38 refs., 7 figs., 1 tab.

  15. The emerging role of meditation in addressing psychiatric illness, with a focus on substance use disorders.

    PubMed

    Dakwar, Elias; Levin, Frances R

    2009-01-01

    Over the past 30 years the practice of meditation has become increasingly popular in clinical settings. In addition to evidence-based medical uses, meditation may have psychiatric benefits. In this review, the literature on the role of meditation in addressing psychiatric issues, and specifically substance use disorders, is discussed. Each of the three meditation modalities that have been most widely studied-transcendental meditation, Buddhist meditation, and mindfulness-based meditation-is critically examined in terms of its background, techniques, mechanisms of action, and evidence-based clinical applications, with special attention given to its emerging role in the treatment of substance use disorders. The unique methodological difficulties that beset the study of meditation are also considered. A brief discussion then integrates the research that has been completed thus far, elucidates the specific ways that meditation may be helpful for substance use disorders, and suggests new avenues for research.

  16. The Emerging Role of Meditation in Addressing Psychiatric Illness, with a Focus on Substance Use Disorders

    PubMed Central

    Dakwar, Elias; Levin, Frances R.

    2011-01-01

    Over the past 30 years the practice of meditation has become increasingly popular in clinical settings. In addition to evidence-based medical uses, meditation may have psychiatric benefits. In this review, the literature on the role of meditation in addressing psychiatric issues, and specifically substance use disorders, is discussed. Each of the three meditation modalities that have been most widely studied—transcendental meditation, Buddhist meditation, and mindfulness-based meditation—is critically examined in terms of its background, techniques, mechanisms of action, and evidence-based clinical applications, with special attention given to its emerging role in the treatment of substance use disorders. The unique methodological difficulties that beset the study of meditation are also considered. A brief discussion then integrates the research that has been completed thus far, elucidates the specific ways that meditation may be helpful for substance use disorders, and suggests new avenues for research. PMID:19637074

  17. Clinical validation of a type-specific real-time quantitative human papillomavirus PCR against the performance of hybrid capture 2 for the purpose of cervical cancer screening.

    PubMed

    Depuydt, C E; Benoy, I H; Beert, J F A; Criel, A M; Bogers, J J; Arbyn, M

    2012-12-01

    To be acceptable for use in cervical cancer screening, a new assay that detects DNA of high-risk human papillomavirus (hrHPV) types must demonstrate high reproducibility and performance not inferior to that of a clinically validated HPV test. In the present study, a real-time quantitative PCR (qPCR) assay targeting the E6 and E7 genes of hrHPV was compared with Hybrid Capture 2 (hc2) in a Belgian cervical cancer screening setting. In women >30 years old, the sensitivity and specificity for intraepithelial neoplasias of grade 2 or worse (93 cases of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) and 1,207 cases of no CIN or CIN1) were 93.6% and 95.6%, respectively, and those of hc2 were 83.9% and 94.5%, respectively {relative sensitivity of qPCR/hc2 = 1.12 [95% confidence interval (CI), 1.01 to 1.23]; relative specificity = 1.01 [95% CI, 0.99 to 1.03]}. A score test showed that the sensitivity (P < 0.0001) and specificity (P < 0.0001) of the qPCR assay were not inferior to those of hc2 at the required thresholds of 90% and 98%, respectively. The overall agreement of hrHPV positivity between the two runs of the qPCR tests was 98.7% (95% CI, 97.5 to 99.4%), with a kappa value of 0.96 (95% CI, 0.83 to 1.00). The qPCR assay used in this study can be considered a reliable HPV assay that fulfills the clinical validation criteria defined for use in cervical cancer screening.

  18. Clinical significance of the prostate-specific antigen doubling time prior to and following radical prostatectomy to predict the outcome of prostate cancer

    PubMed Central

    Takeuchi, Hisashi; Ohori, Makoto; Tachibana, Masaaki

    2017-01-01

    With the advent of serum prostate-specific antigen (PSA), a larger number of prostate cancers in the early phase have been successfully detected. Although decisions to perform prostate biopsies are routinely based on PSA levels, the PSA level is easily influenced by benign prostatic hyperplasia, with poor specificity. Therefore, the aim of the present study was to assess the clinical significance of prostate-specific antigen doubling time (PSADT) prior to and following radical prostatectomy. In total, 488 patients with T1c-3N0M0 prostate cancer who underwent radical prostatectomy were included. Preoperative and postoperative PSADT were retrospectively correlated with pathological and clinical outcomes. Preoperative PSADT was measured in 204 of the 488 patients. In total, 16 out of 20 patients with a preoperative PSADT of >24 months had a cancer confined to the prostate compared with 105 of 184 patients with a PSADT of <24 months. The PSA non-recurrence rate at 5 years for patients with a preoperative PSADT of >24 months was significantly better compared with those with a preoperative PSADT of <24 months (P=0.011). Patients with a PSADT of >24 months and stable PSADT were associated with PSA recurrence following surgery, based on multivariate analysis. Postoperative PSADT was measured in 51 of 111 patients with PSA failure following surgery. Pathologically, 7 of 8 patients with a post-PSADT of >24 months had a cancer confined to the prostate compared with 14 of 43 patients with a post-PSADT of <24 months. These results suggest that patients with longer preoperative PSADTs appeared to have a favorable pathological result and a higher PSA non-recurrence rate compared with those with shorter preoperative PSADTs. A longer postoperative PSADT may facilitate the observation of patients with PSA recurrence without immediate secondary treatments. PMID:28357104

  19. A task-specific interactive game-based virtual reality rehabilitation system for patients with stroke: a usability test and two clinical experiments

    PubMed Central

    2014-01-01

    Background Virtual reality (VR) is not commonly used in clinical rehabilitation, and commercial VR gaming systems may have mixed effects in patients with stroke. Therefore, we developed RehabMaster™, a task-specific interactive game-based VR system for post-stroke rehabilitation of the upper extremities, and assessed its usability and clinical efficacy. Methods A participatory design and usability tests were carried out for development of RehabMaster with representative user groups. Two clinical trials were then performed. The first was an observational study in which seven patients with chronic stroke received 30 minutes of RehabMaster intervention per day for two weeks. The second was a randomised controlled trial of 16 patients with acute or subacute stroke who received 10 sessions of conventional occupational therapy only (OT-only group) or conventional occupational therapy plus 20 minutes of RehabMaster intervention (RehabMaster + OT group). The Fugl-Meyer Assessment score (FMA), modified Barthel Index (MBI), adverse effects, and drop-out rate were recorded. Results The requirements of a VR system for stroke rehabilitation were established and incorporated into RehabMaster. The reported advantages from the usability tests were improved attention, the immersive flow experience, and individualised intervention. The first clinical trial showed that the RehabMaster intervention improved the FMA (P = .03) and MBI (P = .04) across evaluation times. The second trial revealed that the addition of RehabMaster intervention tended to enhance the improvement in the FMA (P = .07) but did not affect the improvement in the MBI. One patient with chronic stroke left the trial, and no adverse effects were reported. Conclusions The RehabMaster is a feasible and safe VR system for enhancing upper extremity function in patients with stroke. PMID:24597650

  20. Addressing the water budget with SMOS

    NASA Astrophysics Data System (ADS)

    Kerr, Y. H.; AlBitar, A.; Tomer, S. K.; Merlin, O.; Pellarin, T.

    2012-12-01

    SMOS, a L Band radiometer using aperture synthesis to achieve a good spatial resolution, was successfully launched on November 2, 2009. It was developed and made under the leadership of the European Space Agency (ESA) as an Earth Explorer Opportunity mission. It is a joint program with the Centre National d'Etudes Spatiales (CNES) in France and the Centro para el Desarrollo Teccnologico Industrial (CDTI) in Spain. SMOS carries a single payload, an L band 2D interferometric,radiometer in the 1400-1427 MHz h protected band. This wavelength penetrates well through the vegetation and the atmosphere is almost transparent enabling to infer both soil moisture and vegetation water content. SMOS achieves an unprecedented spatial resolution of 50 km at L-band maximum (43 km on average) with multi angular-dual polarized (or fully polarized) brightness temperatures over the globe and with a revisit time smaller than 3 days. SMOS as been now acquiring data for almost 2 years. The data quality exceeds what was expected, showing very good sensitivity and stability. The data is however very much impaired by man made emission in the protected band, leading to degraded measurements in several areas including parts of Europe and of China. However, many different international teams are now addressing cal val activities in various parts of the world, with notably large field campaigns either on the long time scale or over specific targets to address the specific issues. In parallel different teams are now starting addressing data use in various fields including hydrology. It requires coupling with other models and or disaggregation to address soil moisture distribution over watersheds. Significant new results were obtained for floods and drought events, together with new potential applications in terms of precipitation monitoring This paper thus gives an overview of the science goals of the SMOS mission, a description of its main elements, and a taste of the first results including

  1. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone

    PubMed Central

    SALIDO-GUADARRAMA, ALBERTO IVAN; MORALES-MONTOR, JORGE GUSTAVO; RANGEL-ESCAREÑO, CLAUDIA; LANGLEY, ELIZABETH; PERALTA-ZARAGOZA, OSCAR; COLIN, JOSE LUIS CRUZ; RODRIGUEZ-DORANTES, MAURICIO

    2016-01-01

    At present, prostate-specific antigen (PSA) is used as a clinical biomarker for prostate cancer (PCa) diagnosis; however, a large number of patients with benign prostate hyperplasia (BPH) with PSA levels in the ʻgray areaʼ (4–10 ng/ml) are currently subjected to unnecessary biopsy due to overdiagnosis. Certain microRNAs (miRs) have been proven to be useful biomarkers, several of which are detectable in bodily fluids. The present study identified and validated a urinary miR-based signature to enhance the specificity of PCa diagnosis and to reduce the number of patients with benign conditions undergoing biopsy. Seventy-three urine samples from Mexican patients with diagnosis of PCa with a Gleason score ≥7 and 70 patients diagnosed with BPH were collected after digital rectal examination (DRE) of the prostate. miR expression profiles were determined using TaqMan Low Density Array experiments, and normalized Ct values for the miRs were compared between PCa and BPH groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether miR detection in urine is suitable for distinguishing patients with PCa from those with BPH. The identified miR-100/200b signature was significantly correlated with PCa. Using a multivariable logistic regression approach, a base model including the clinical variables age, prostate-specific antigen (PSA), the percentage of free PSA and DRE was generated, and a second base model additionally contained the miR-100/200b signature. ROC analysis demonstrated that the combined model significantly outperformed the capacity of PSA (P<0.001) and the base model (P=0.01) to discriminate between PCa and BPH patients. In terms of evaluation of the sub-group of patients in the gray zone of PSA levels, the performance of the combined model for predicting PCa cases was significantly superior to PSA level determination (P<0.001) and the base model (P=0.009). In addition, decision curve analysis demonstrated that the use of

  2. Defusion: A Behavior-Analytic Strategy for Addressing Private Events

    PubMed Central

    Snyder, Katie; Lambert, Joseph; Twohig, Michael P

    2011-01-01

    Applied behavior analysts encounter situations in which private events hinder client progress, and additional techniques to address these issues are needed. By conceptualizing private events as verbal rules, we provide a behavior-analytic framework for understanding and addressing these events. Relational frame theory (RFT) is the basis for this conceptual foundation; the empirically based principles of RFT are presented along with direct implications for understanding private events. Defusion, an RFT-based technique for addressing private events, is then described and empirical studies that evaluate the effects of defusion are reviewed. Finally, potential clinical applications for practicing behavior analysts are offered. PMID:22649574

  3. TESTING POPULATION-SPECIFIC QUANTITATIVE TRAIT ASSOCIATIONS FOR CLINICAL OUTCOME RELEVANCE IN A BIOREPOSITORY LINKED TO ELECTRONIC HEALTH RECORDS: LPA AND MYOCARDIAL INFARCTION IN AFRICAN AMERICANS

    PubMed Central

    Dumitrescu, Logan; Diggins, Kirsten E.; Goodloe, Robert; Crawford, Dana C.

    2015-01-01

    Previous candidate gene and genome-wide association studies have identified common genetic variants in LPA associated with the quantitative trait Lp(a), an emerging risk factor for cardiovascular disease. These associations are population-specific and many have not yet been tested for association with the clinical outcome of interest. To fill this gap in knowledge, we accessed the epidemiologic Third National Health and Nutrition Examination Surveys (NHANES III) and BioVU, the Vanderbilt University Medical Center biorepository linked to de-identified electronic health records (EHRs), including billing codes (ICD-9-CM) and clinical notes, to test population-specific Lp(a)-associated variants for an association with myocardial infarction (MI) among African Americans. We performed electronic phenotyping among African Americans in BioVU ≥40 years of age using billing codes. At total of 93 cases and 522 controls were identified in NHANES III and 265 cases and 363 controls were identified in BioVU. We tested five known Lp(a)-associated genetic variants (rs1367211, rs41271028, rs6907156, rs10945682, and rs1652507) in both NHANES III and BioVU for association with myocardial infarction. We also tested LPA rs3798220 (I4399M), previously associated with increased levels of Lp(a), MI, and coronary artery disease in European Americans, in BioVU. After meta-analysis, tests of association using logistic regression assuming an additive genetic model revealed no significant associations (p<0.05) for any of the five LPA variants previously associated with Lp(a) levels in African Americans. Also, I4399M rs3798220 was not associated with MI in African Americans (odds ratio = 0.51; 95% confidence interval: 0.16 – 1.65; p=0.26) despite strong, replicated associations with MI and coronary artery disease in European American genome-wide association studies. These data highlight the challenges in translating quantitative trait associations to clinical outcomes in diverse populations

  4. Clinical isolates of Enterococcus faecium exhibit strain-specific collagen binding mediated by Acm, a new member of the MSCRAMM family.

    PubMed

    Nallapareddy, Sreedhar R; Weinstock, George M; Murray, Barbara E

    2003-03-01

    A collagen-binding adhesin of Enterococcus faecium, Acm, was identified. Acm shows 62% similarity to the Staphylococcus aureus collagen adhesin Cna over the entire protein and is more similar to Cna (60% and 75% similarity with Cna A and B domains respectively) than to the Enterococcus faecalis collagen-binding adhesin, Ace, which shares homology with Acm only in the A domain. Despite the detection of acm in 32 out of 32 E. faecium isolates, only 11 of these (all clinical isolates, including four vancomycin-resistant endocarditis isolates and seven other isolates) exhibited binding to collagen type I (CI). Although acm from three CI-binding vancomycin-resistant E. faecium clinical isolates showed 100% identity, analysis of acm genes and their promoter regions from six non-CI-binding strains identified deletions or mutations that introduced stop codons and/or IS elements within the gene or the promoter region in five out of six strains, suggesting that the presence of an intact functional acm gene is necessary for binding of E. faecium strains to CI. Recombinant Acm A domain showed specific and concentration-dependent binding to collagen, and this protein competed with E. faecium binding to immobilized CI. Consistent with the adherence phenotype and sequence data, probing with Acm-specific IgGs purified from anti-recombinant Acm A polyclonal rabbit serum confirmed the surface expression of Acm in three out of three collagen-binding clinical isolates of E. faecium tested, but in none of the strains with a non-functional pseudo acm gene. Introduction of a functional acm gene into two non-CI-binding natural acm mutant strains conferred a CI-binding phenotype, further confirming that native Acm is sufficient for the binding of E. faecium to CI. These results demonstrate that acm, which encodes a potential virulence factor, is functional only in certain infection-derived clinical isolates of E. faecium, and suggest that Acm is the primary adhesin responsible for the

  5. Addressing the Needs of Students with Rett Syndrome.

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Ellenburg, Jennifer S.; Acton, Olivia M.; Torrey, Gregory

    2001-01-01

    This article discusses symptoms of students with Rett Syndrome, a disability in females characterized by the development of multiple specific deficits following a period of normal functioning after birth. Specific interventions for students with Rett syndrome are provided and address communication, stereotypic movements, self-injurious behaviors,…

  6. Presidential address. Fatti Maschii Parole Femine.

    PubMed

    Murphy, G P

    1984-03-15

    The current role of the Society of Surgical Oncology has demonstrated leadership in the field of surgical oncology in both word and deed, as exemplified by the motto of the State of Maryland, adopted from the 1632 family seal of Lord Baltimore, "Fatti Maschii Parole Femine." The current emphasis on the need for clinical research on human cancers, and the education of surgeons in all aspects of various cancers is well founded in the writings and the addresses of Dr. James Ewing, the Society's founder. Our goals as a society for the next decade have been precisely defined and, as in all important national programs, made current and interfaced with corresponding priorities of the American Cancer Society and the National Cancer Institute. The Society, in three project areas, is: (1) assessing current progress in surgical oncology, as well as future manpower needs; (2) studying on a comprehensive basis the surgical practices in cancer patient management; and (3) surveying academic centers concerning the nature of current education and training of academic surgeons in clinical research. The Training Committee currently reviews and recognizes 2-year postresidency multidisciplinary training at several institutions, and the James Ewing Foundation has expanded its fiscal support of educational activities. This annual meeting marks an historic first signified by the conjoint sessions being held with other international surgical oncology societies.

  7. A Division of Research in an Academic Clinical Department.

    ERIC Educational Resources Information Center

    Traystman, Richard J.

    1982-01-01

    Discusses in general the importance of a research division, whether basic or clinical, in an academic setting and factors to consider in establishing one. Uses John Hopkins' newly created research division for Anesthesiology and Critical Care Medicine to specifically address funding and intra- and interdepartmental clinical research programs. (DC)

  8. HLA-DRB1*03, DRB1*11 or DRB1*12 and their respective DRB3 specificities in clinical variants of sarcoidosis.

    PubMed

    Bogunia-Kubik, K; Tomeczko, J; Suchnicki, K; Lange, A

    2001-01-01

    Determination of DRB1 and DRB3 specificities in sarcoidosis patients identified that the presence of DRB1*03 and the absence of DRB1*11 and/or DRB1*12 favors a course of disease that is associated positively with Löfgren's syndrome (DRB1*03) and negatively with stage I disease (DRB1*11 and/or 12). In common with normal controls, DRB1*03 was associated with DRB3*0101 and DRB1*11/12 with DRB3*0201/2. An analysis of DRB1 and DRB3 associations in variants of sarcoidosis revealed that DRB1*03 and DRB3*0101 were associated with Löfgren's syndrome in a combined association fashion. Conversely, a lack of DRB1*11 and/or DRB1*12 but not DRB3*0201/2 favored the clinical course of sarcoidosis.

  9. A strategy to address the nursing faculty shortage.

    PubMed

    Ganley, Barbara J; Sheets, Ingrid

    2009-07-01

    This article describes one university's experience in creating a master's geriatric clinical nurse specialist-nurse educator program to address the nursing faculty shortage and the need for geriatric clinical nurse specialists. The successes and challenges are outlined, and curricular ideas that may be beneficial to other nursing programs also are presented. This program has enhanced the university's pool of clinical instructors, increased its ability to provide services to older adults, and allowed faculty to instruct and focus undergraduates in the distinctions of geriatric nursing care. The biggest challenges faced were marketing and recruitment of nurses; these challenges were addressed, and possible solutions are offered. The most immediate benefit of this program was the generation of geriatric clinical nurse specialists.

  10. In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer.

    PubMed

    Hirano, Toshiyuki; Yasuda, Hiroyuki; Tani, Tetsuo; Hamamoto, Junko; Oashi, Ayano; Ishioka, Kota; Arai, Daisuke; Nukaga, Shigenari; Miyawaki, Masayoshi; Kawada, Ichiro; Naoki, Katsuhiko; Costa, Daniel B; Kobayashi, Susumu S; Betsuyaku, Tomoko; Soejima, Kenzo

    2015-11-17

    EGFR mutated lung cancer accounts for a significant subgroup of non-small-cell lung cancer (NSCLC). Over the last decade, multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) have been developed to target mutated EGFR. However, there is little information regarding mutation specific potency of EGFR-TKIs against various types of EGFR mutations. The purpose of this study is to establish an in vitro model to determine the "therapeutic window" of EGFR-TKIs against various types of EGFR mutations, including EGFR exon 20 insertion mutations. The potency of 1st (erlotinib), 2nd (afatinib) and 3rd (osimertinib and rociletinib) generation EGFR-TKIs was compared in vitro for human lung cancer cell lines and Ba/F3 cells, which exogenously express mutated or wild type EGFR. An in vitro model of mutation specificity was created by calculating the ratio of IC50 values between mutated and wild type EGFR. The in vitro model identified a wide therapeutic window of afatinib for exon 19 deletions and L858R and of osimertinib and rociletinib for T790M positive mutations. The results obtained with our models matched well with previously reported preclinical and clinical data. Interestingly, for EGFR exon 20 insertion mutations, most of which are known to be resistant to 1st and 2nd generation EGFR-TKIS, osimertinib was potent and presented a wide therapeutic window. To our knowledge, this is the first report that has identified the therapeutic window of osimertinib for EGFR exon 20 insertion mutations. In conclusion, this model will provide a preclinical rationale for proper selection of EGFR-TKIs against clinically-relevant EGFR mutations.

  11. Biophysical and biological characterization of a new line of hyaluronan-based dermal fillers: A scientific rationale to specific clinical indications.

    PubMed

    La Gatta, Annalisa; De Rosa, Mario; Frezza, Maria Assunta; Catalano, Claudia; Meloni, Marisa; Schiraldi, Chiara

    2016-11-01

    Chemico-physical and biological characterization of hyaluronan-based dermal fillers is of key importance to differentiate between numerous available products and to optimize their use. These studies on fillers are nowadays perceived as a reliable approach to predict their performance in vivo. The object of this paper is a recent line of hyaluronic acid (HA)-based dermal fillers, Aliaxin®, available in different formulations that claim a complete facial restoration. The aim of the study is to provide biophysical and biological data that may support the clinical indications and allow to predict performance possibly with respect to similar available products. Aliaxin® formulations were tested for their content in soluble HA, water uptake capacity, rheological behavior, stability to enzymatic degradation, and for in vitro capacity to stimulate extracellular matrix components production. The formulations were found to contain a low amount of soluble HA and were equivalent to each other regarding insoluble hydrogel concentration. The different crosslinking degree declared by the producer was consistent with the trend in water uptake capacity, rigidity, viscosity. No significant differences in stability to enzymatic hydrolysis were found. In vitro experiments, using a full thickness skin model, showed an increase in collagen production in the dermoepidermal junction. Results support the claims of different clinical indications, the classification of products regarding hydro-, lift-action and the specifically suggested needle gauge for the delivery. The biological outcomes also support products effectiveness in skin structure restoration. These data predicted a better performance regarding hydro-action, tissue integration, clinical management during delivery, and a high durability of the aesthetic effect when compared to data on marketed similar products.

  12. A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia).

    PubMed

    Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

    2017-01-01

    Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients' and their family's quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

  13. A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia)

    PubMed Central

    Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

    2017-01-01

    Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success. PMID:28243068

  14. An address geocoding solution for Chinese cities

    NASA Astrophysics Data System (ADS)

    Zhang, Xuehu; Ma, Haoming; Li, Qi

    2006-10-01

    We introduce the challenges of address geocoding for Chinese cities and present a potential solution along with a prototype system that deal with these challenges by combining and extending current geocoding solutions developed for United States and Japan. The proposed solution starts by separating city addresses into "standard" addresses which meet a predefined address model and non-standard ones. The standard addresses are stored in a structured relational database in their normalized forms, while a selected portion of the non-standard addresses are stored as aliases to the standard addresses. An in-memory address index is then constructed from the address database and serves as the basis for real-time address matching. Test results were obtained from two trials conducted in the city Beijing. On average 80% matching rate were achieved. Possible improvements to the current design are also discussed.

  15. The significance of addressing trauma in outpatient psychiatry.

    PubMed

    Al-Saffar, S; Borgå, P; Lawoko, S; Edman, G; Hällström, T

    2004-01-01

    Establishing post-traumatic stress disorder as a psychiatric diagnosis has only marginally increased awareness of traumatic experiences. Traumas are inconsistently recorded in initial psychiatric histories and, when observed, rarely reflected in the primary diagnosis and treatment. The present study aimed to investigate if there is an association between sufficiently addressing trauma and long-term outcome and what factors affect whether trauma, according to the patient's view, is sufficiently addressed or not. Socio-demographic data, experiences of trauma and treatment, and outcome, were collected retrospectively from Arabic, Iranian, Turkish and Swedish patients, who had visited a psychiatric clinic 3-4 years earlier. Fifty-one patients whose traumatic experiences had been sufficiently addressed were compared with 39 patients who perceived that their traumas had not been addressed. Logistic regression analyses were performed to examine relationships between clinical variables and whether or not traumas had been addressed. Patients with trauma sufficiently addressed reported high confidence in staff (odds ratio, OR=7.2, p<0.001), high self-rated health (OR=8.0, p<0.01) and low scores on the Self-rating Inventory for PTSD (OR=7.7, p<0.05) and Depression Scale (OR=3.0, p<0.15). Reporting less than five different traumas (OR=4.6, p<0.01) and being an ethnic Swede (OR=2.4, p<0.10) were the background variables independently related to having trauma sufficiently addressed. Addressing trauma may improve patients' confidence in staff, self-rated health and trauma-related symptoms. Multiplicity of traumas and belonging to an ethnic minority implied that trauma was less addressed.

  16. Specific personality traits and general personality dysfunction as predictors of the presence and severity of personality disorders in a clinical sample.

    PubMed

    Berghuis, Han; Kamphuis, Jan H; Verheul, Roel

    2014-01-01

    This study examined the associations of specific personality traits and general personality dysfunction in relation to the presence and severity of Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) personality disorders in a Dutch clinical sample. Two widely used measures of specific personality traits were selected, the Revised NEO Personality Inventory as a measure of normal personality traits, and the Dimensional Assessment of Personality Pathology-Basic Questionnaire as a measure of pathological traits. In addition, 2 promising measures of personality dysfunction were selected, the General Assessment of Personality Disorder and the Severity Indices of Personality Problems. Theoretically predicted associations were found between the measures, and all measures predicted the presence and severity of DSM-IV personality disorders. The combination of general personality dysfunction models and personality traits models provided incremental information about the presence and severity of personality disorders, suggesting that an integrative approach of multiple perspectives might serve comprehensive assessment of personality disorders.

  17. Differentiating cognitive functions of poststroke patients with specific brain lesions: A preliminary study on the clinical utility of Cognistat-P.

    PubMed

    Chan, Sam C C; Chan, Chetwyn C H; Wu, Yi; Liu, Karen P Y; Xu, Yan-Wen

    2016-01-01

    The Cognistat is widely used to measure the cognitive profile of neurological patients. This study aimed to further obtain evidence on the construct and discriminative validity of the Putonghua version of the Cognistat (Cognistat-P) on poststroke patients with specific brain lesions. Cognistat-P was administered to poststroke patients (n = 98), as well as healthy elderly (n = 40) and adult (n = 34) participants as the control groups. Poststroke patients were further categorized into 4 lesion groups using standard brain slice templates. Exploratory factory analysis reflected a 2-factor structure for the Cognistat-P that resembles that for the original English version. The Construction, Similarities, and Judgment subtests were found to differentiate patients with frontal or parietal lesions from those with subcortical lesions (p < .01, R(2) = .48). The Construction subtest, tapping the "fluid" ability, was the most useful for differentiating patients with parietal lesions from those with subcortical lesions. The Similarities subtest together with the Construction subtest was the most useful for differentiating patients with frontal lesions from those with subcortical lesions. This study established the validity of the Cognistat-P for differentiating poststroke patients with specific brain lesions. Future studies should replicate the results on a larger sample size and test the clinical significance of the Cognistat-P profiles.

  18. Addressable-Matrix Integrated-Circuit Test Structure

    NASA Technical Reports Server (NTRS)

    Sayah, Hoshyar R.; Buehler, Martin G.

    1991-01-01

    Method of quality control based on use of row- and column-addressable test structure speeds collection of data on widths of resistor lines and coverage of steps in integrated circuits. By use of straightforward mathematical model, line widths and step coverages deduced from measurements of electrical resistances in each of various combinations of lines, steps, and bridges addressable in test structure. Intended for use in evaluating processes and equipment used in manufacture of application-specific integrated circuits.

  19. The clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer: incremental value versus mammography.

    PubMed

    Spanu, Angela; Sanna, Daniela; Chessa, Francesca; Manca, Alessandra; Cottu, Pierina; Fancellu, Alessandro; Nuvoli, Susanna; Madeddu, Giuseppe

    2012-08-01

    We investigated the clinical impact of breast scintigraphy acquired with a breast specific γ-camera (BSGC) in the diagnosis of breast cancer (BC) and assessed its incremental value over mammography (Mx). A consecutive series of 467 patients underwent BSGC scintigraphy for different indications: suspicious lesions on physical examination and/or on US/MRI negative at Mx (BI-RADS 1 or 3), characterization of lesions suspicious at Mx (BI-RADS 4), preoperative staging in lesions highly suggestive of malignancy at Mx (BI-RADS 5). Definitive histopathological findings were obtained in all cases after scintigraphy: 420/467 patients had BC, while 47/467 patients had benign lesions. The scintigraphic data were correlated to Mx BI-RADS category findings and to histology. The incremental value of scintigraphy over Mx was calculated. Scintigraphy was true-positive in 97.1% BC patients, detecting 96.2% of overall tumor foci, including 91.5% of carcinomas ≤10 mm, and it was true-negative in 85.1% of patients with benign lesions. Scintigraphy gave an additional value over Mx in 141/467 cases (30.2%). In particular, scintigraphy ascertained BC missed at Mx in 31 patients with BI-RADS 1 or 3, including 26 patients with heterogeneously/high dense breast (19/26 with tumors ≤10 mm) and detected additional clinically occult ipsilateral or controlateral tumor foci (all <10 mm) or the in situ component sited around invasive tumors in 77 BC patients with BI-RADS 4 or 5, changing surgical management in 18.2% of these cases; moreover, scintigraphy ruled out malignancy in 33 patients with BI-RADS 4. BSGC scintigraphy proved a highly sensitive diagnostic tool, even in small size carcinoma detection, while maintaining a high specificity. The procedure increased both the sensitivity of Mx, especially in dense breast and in multifocal/multicentric disease, and the specificity as well as it better defined local tumor extension, thus guiding the surgeon to a more appropriate surgical treatment.

  20. Addressing Family Smoking in Child Health Care Settings

    PubMed Central

    Hall, Nicole; Hipple, Bethany; Friebely, Joan; Ossip, Deborah J.; Winickoff, Jonathan P.

    2009-01-01

    Objective To discuss strategies for integrating evidence-based tobacco use screening, cessation assistance, and referral to outside services into visits with families in outpatient child health care settings. Methods Presentation of counseling scenarios used in the Clinical Effort Against Secondhand Smoke Exposure (CEASE) training video and commentary. Results Demonstrated strategies include: eliciting information about interest and readiness to quit smoking, respectfully setting an agenda to discuss smoking, tailoring advice and education to the specific circumstances, keeping the dialogue open, prescribing cessation medication, helping the smoker set an action plan for cessation, enrolling the smoker in free telephone counseling through the state quitline, and working with family members to establish a completely smoke-free home and car. Video demonstrations of these techniques are available at www.ceasetobacco.org. Conclusion Child health care clinicians have a unique opportunity to address family smoking and can be most effective by adapting evidence-based tobacco cessation counseling strategies for visits in the pediatric setting. PMID:20448841

  1. Addressing concerns and achieving expectations

    SciTech Connect

    Miller, C.L.

    1995-12-01

    Approximately 2-1/2 years ago many of us were gathered here in Prague at a similar conference with a similar name, {open_quotes}Energy and Environment: Transitions in Eastern Europe.{close_quotes} Over 300 professionals from 26 nations attended. The objective of the conference was to: Facilitate the Solution of Long and Short Term Energy and Environmental Problems in Eastern Europe by Bringing Together People, ideas and technologies which could be applied to specific problems in a logical step-by-step manner. It was conceded at the time that the long term solution would consist of thoughtfully integrated steps and that the conference was the first step. We are here in the Czech Republic again this week to continue what was started. As before, this conference continues to: (1) Provide a forum to identify and discuss cost-effective environmentally acceptable energy and environmental technology options and their associated socioeconomic issues. (2) Stimulate the Formation of business partnerships (3) Identify key barrier issues hindering technology applications and identify implementation pathways that eliminate or avoid obstacles to progress.

  2. Innovative clinical trial design for pediatric therapeutics

    PubMed Central

    Laughon, Matthew M; Benjamin, Daniel K; Capparelli, Edmund V; Kearns, Gregory L; Berezny, Katherine; Paul, Ian M; Wade, Kelly; Barrett, Jeff; Smith, Phillip Brian; Cohen-Wolkowiez, Michael

    2011-01-01

    Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and ‘opportunistic’ studies, have addressed some of the historical challenges associated with clinical trials in children. PMID:21980319

  3. Addressing Free Radical Oxidation in Acne Vulgaris

    PubMed Central

    Criscito, Maressa C.; Schlesinger, Todd E.; Verdicchio, Robert; Szoke, Ernest

    2016-01-01

    Objective: Comparatively little attention has been paid to the role of free radical oxidation in acne vulgaris. Here, using the traditional abnormalities cited for acne, the authors address the role of free radical oxidation throughout the pathogenesis by detailing the chemistry that may contribute to clinical changes. To probe the effects of free radical oxidation and test an antioxidant, they conducted a preliminary study of topically applied vitamin E. Methods: Seventeen patients with mild-to-moderate acne vulgaris were evaluated over an eight-week period in two private dermatology practices in this open-label study. All patients enrolled were on the same baseline regimen of salicylic acid and benzoyl peroxide. This regimen was then supplemented with topical vitamin E in sunflower seed oil. Results: At the end of the eight-week period, all patients demonstrated clinical improvement, as indicated by a reduction in the number of lesions and global mean difference. A statistically significant reduction was noted as early as Week 2. Enrolled patients also expressed a positive experience due to good tolerability and easy application. Conclusion: Although the exact pathogenesis of acne vulgaris remains unknown, the presence of excessive reactive oxygen species can be implicated in each of the major abnormalities involved. This presence, along with the positive results of the authors’ preliminary study, demonstrates the need for more exploration on the use of topical antioxidants in limiting free radical oxidation in the acne model. This paper is designed to stimulate academic discussion regarding a new way of thinking about the disease state of acne. PMID:26962389

  4. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Official address. The principal office of the Commission is at Washington, DC. All communications to the Commission should be addressed to the Federal Trade Commission, 600 Pennsylvania Avenue, NW, Washington,...

  5. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Official address. The principal office of the Commission is at Washington, DC. All communications to the Commission should be addressed to the Federal Trade Commission, 600 Pennsylvania Avenue, NW, Washington,...

  6. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Official address. The principal office of the Commission is at Washington, DC. All communications to the Commission should be addressed to the Federal Trade Commission, 600 Pennsylvania Avenue, NW, Washington,...

  7. Prevalence, Clinical Profile, Iron Status, and Subject-Specific Traits for Excessive Erythrocytosis in Andean Adults Living Permanently at 3,825 Meters Above Sea Level

    PubMed Central

    De Ferrari, Aldo; Miranda, J. Jaime; Gilman, Robert H.; Dávila-Román, Victor G.; León-Velarde, Fabiola; Rivera-Ch, Maria; Huicho, Luis; Bernabé-Ortiz, Antonio; Wise, Robert A.

    2014-01-01

    BACKGROUND: Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. METHODS: We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. RESULTS: Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P < .001) but no difference was found in iron status indicators between both groups (P > .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40-41.80) were strongly associated with EE. Attributable fractions for EE were greatest for being overweight (26.7%), followed by male sex (21.5%), pulse oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC < 80% (9.3%). CONCLUSIONS: We found a lower prevalence of EE than in previous reports in the Peruvian Andes. Although the presence of hypoxemia and decreased vital capacity were strongly associated with excessive erythrocytosis, being overweight or having metabolic syndrome were associated with an important fraction of cases in our study population. PMID

  8. Engineering nanomaterials to address cell-mediated inflammation in atherosclerosis

    PubMed Central

    Allen, Sean; Liu, Yu-Gang; Scott, Evan

    2016-01-01

    Atherosclerosis is an inflammatory disorder with a pathophysiology driven by both innate and adaptive immunity and a primary cause of cardiovascular disease (CVD) worldwide. Vascular inflammation and accumulation of foam cells and their products induce maturation of atheromas, or plaques, which can rupture by metalloprotease action, leading to ischemic stroke or myocardial infarction. Diverse immune cell populations participate in all stages of plaque maturation, many of which directly influence plaque stability and rupture via inflammatory mechanisms. Current clinical treatments for atherosclerosis focus on lowering serum levels of low-density lipoprotein (LDL) using therapeutics such as statins, administration of antithrombotic drugs, and surgical intervention. Strategies that address cell-mediated inflammation are lacking, and consequently have recently become an area of considerable research focus. Nanomaterials have emerged as highly advantageous tools for these studies, as they can be engineered to target specific inflammatory cell populations, deliver therapeutics of wide-ranging solubilities and enhance analytical methods that include imaging and proteomics. Furthermore, the highly phagocytic nature of antigen presenting cells (APCs), a diverse cell population central to the initiation of immune responses and inflammation, make them particularly amenable to targeting and modulation by nanoscale particulates. Nanomaterials have therefore become essential components of vaccine formulations and treatments for inflammation-driven pathologies like autoimmunity, and present novel opportunities for immunotherapeutic treatments of CVD. Here, we review recent progress in the design and use of nanomaterials for therapeutic assessment and treatment of atherosclerosis. We will focus on promising new approaches that utilize nanomaterials for cell-specific imaging, gene therapy and immunomodulation. PMID:27135051

  9. Is Fc gamma receptor IIA (FcγRIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?

    PubMed

    Cherif, Mariama K; Sanou, Guillaume S; Bougouma, Edith C; Diarra, Amidou; Ouédraogo, Alphonse; Dolo, Amagana; Troye-Blomberg, Marita; Cavanagh, David R; Theisen, Michael; Modiano, David; Sirima, Sodiomon B; Nebié, Issa

    2015-02-01

    In the present study, the influences of FcγRIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the FcγRIIA-131R/R and FcγRIIA-131R/H allele, whereas the number of FcγRIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the FcγRIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and FcγRIIA polymorphism (p=0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p=0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p=0.003) and to MSP2a (p=0.006); IgG3 to MSP2a (p=0.007) and to GLURP R0 (p=0.044); IgG2 to MSP2b (p=0.007) and IgG4 to MSP3 (p=0.051) and to MSP2a (p=0.049). In this study, homozygous carriers of the FcγRIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers FcγRIIA-131R/H alleles and to homozygous carriers of FcγRIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria.

  10. Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

    NASA Astrophysics Data System (ADS)

    Salgaonkar, Vasant A.; Wootton, Jeff; Prakash, Punit; Scott, Serena; Hsu, I. C.; Diederich, Chris J.

    2017-03-01

    This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (˜7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 - 3 W/cm2 and lasted for 60 - 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 - 12 thermocouple sensors in the HTV and patient-specific 3D thermal modeling based on finite element methods (FEM) was used to supplement limited thermometry. Patient anatomy, heating device positions, orientations, and thermometry junction locations were obtained from patient CT scans and HDR and hyperthermia planning software. The numerical models utilized the applied power levels recorded during the treatments. Tissue properties such as perfusion and acoustic absorption were varied within physiological ranges such that squared-errors between measured and simulated temperatures were minimized. This data-fitting was utilized for 6 HT treatments to estimate volumetric temperature distributions achieved in the HTV and surrounding anatomy devoid of thermocouples. For these treatments, the measured and simulated T50 values in the hyperthermia target volume (HTV) were between 40.1 - 43.9 °C and 40.3 - 44.9 °C, respectively. Maximum temperatures between 46.8 - 49.8 °C were measured during

  11. SkBQ - prooxidant addressed to mitochondria.

    PubMed

    Vyssokikh, M Y; Chernyak, B V; Domnina, L V; Esipov, D S; Ivanova, O Y; Korshunova, G A; Symonyan, R A; Skulachev, M V; Zinevich, T V; Skulachev, V P

    2013-12-01

    Oxidative stress and mitochondrial dysfunction are the key links in the chain of development of pathologies associated with the violation of cellular energy metabolism. Development of mitochondria-addressed compounds highly specific for chemical processes is one of the most promising ways to develop approaches to the treatment of inherited and age-related diseases with mitochondrial etiology. Correlation of structure and chemical activity of the test compounds from a class of lipophilic cations revealed the key role of substituents in the aromatic ring of 1,4-benzoquinones in the manifestation of high antioxidant properties. In this work, it is shown that a synthesized benzoquinone derivative conjugated in position 6 with membrane-penetrating cation of decyltriphenylphosphonium and with substituents at position 2, 3, and 5 (SkBQ) has much lower antioxidant and significantly higher prooxidant activity in comparison with similar derivatives of plasto- and toluquinone SkQ1 and SkQT1 in experiments on isolated mitochondria. At the same time, SkBQ, like SkQ1 and SkQT1, can be reduced by the respiratory chain in the center i of complex III and decrease the mitochondrial membrane potential. In cell cultures of human fibroblasts, it was revealed that SkBQ does not protect cells from apoptosis induced by hydrogen peroxide. Under the same conditions, SkQ1 and SkQT1 exhibit a powerful protective effect. Thus, SkBQ can be seen as a mitochondria-addressed prooxidant. The possibility of using SkBQ as an anticancer drug for the treatment of cancers such as prostate cancer whose cells are sensitive to mitochondrial reactive oxygen species is discussed.

  12. Gentle interruptions: transformative approaches to clinical teaching.

    PubMed

    McAllister, Margaret; Tower, Marion; Walker, Rachel

    2007-07-01

    This conceptual article, drawn from the authors' shared teaching experiences and recent student and clinician evaluation data, set out to reveal and then address some common problems faced by clinical educators and nursing students in the time-constrained, complex, specialized field of clinical learning. We explain and argue the benefits of transformative learning and outline specific strategies for building skills in transformative education, such as interrogating clinical routines and habits, teaching diplomacy skills, and using a process of interruption. Clinical educators can use these strategies to move beyond unwittingly serving the status quo toward consciously contributing to change.

  13. Addressing health literacy in patient decision aids

    PubMed Central

    2013-01-01

    in which health literacy needs were addressed. Conclusion Lower health literacy affects key decision-making outcomes, but few existing PtDAs have addressed the needs of lower health literacy users. The specific effects of PtDAs designed to mitigate the influence of low health literacy are unknown. More attention to the needs of patients with lower health literacy is indicated, to ensure that PtDAs are appropriate for lower as well as higher health literacy patients. PMID:24624970

  14. Addressing submarine geohazards through scientific drilling

    NASA Astrophysics Data System (ADS)

    Camerlenghi, A.

    2009-04-01

    eruptions, earthquakes and the associated tsunamis can lead to destruction of seafloor structures potentially capable of releasing hydrocarbon pollutants into Mediterranean waters, and damage to a dense telecommunication cables net that would cause severe economic loss. However, the most devastating effect would be that of earthquake or landslide-induced tsunamis. When compared to other basins, the Mediterranean has larger vulnerability due to its small dimensions, resulting in close proximity to tsunami sources and impact areas. Recent examples include the 1979 Nice airport submarine landslide and tsunami and the 2002 Stromboli volcano landslide and tsunami. Future international scientific drilling must include submarine geohazards among priority scientific objectives. The science advisory structure must be prepared to receive and evaluate proposal specifically addressing submarine geohazards. The implementing organizations need to be prepared for the technological needs of drilling proposals addressing geohazards. Among the most relevant: geotechnical sampling, down-hole logging at shallow depths below the seafloor, in situ geotechnical and physical measurements, capability of deployment of long-term in situ observatories. Pre-site surveys will often aim at the highest possible resolution, three dimensional imaging of the seafloor ant its sub-surface. Drilling for submarine geohazards is seen as an opportunity of multiplatform drilling, and for Mission Specific drilling in particular. Rather than turning the scientific investigation in a purely engineering exercise, proposals addressing submarine geohazards should offer an opportunity to scientists and engineers to work together to unravel the details of basic geological processes that may turn into catastrophic events.

  15. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  16. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  17. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  18. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  19. 47 CFR 97.23 - Mailing address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mailing address. 97.23 Section 97.23 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO... name and mailing address. The mailing address must be in an area where the amateur service is...

  20. 37 CFR 41.10 - Correspondence addresses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Correspondence addresses. 41... Correspondence addresses. Except as the Board may otherwise direct, (a) Appeals. Correspondence in an application... correspondence in an application or a patent involved in an appeal to the Board for which an address is...

  1. 37 CFR 41.10 - Correspondence addresses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Correspondence addresses. 41... Correspondence addresses. Except as the Board may otherwise direct, (a) Appeals. Correspondence in an application... correspondence in an application or a patent involved in an appeal to the Board for which an address is...

  2. 47 CFR 13.10 - Licensee address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Licensee address. 13.10 Section 13.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.10 Licensee address. In accordance with § 1.923 of this chapter all applications must specify an address where...

  3. 32 CFR 516.7 - Mailing addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Mailing addresses. 516.7 Section 516.7 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND PUBLIC RELATIONS LITIGATION General § 516.7 Mailing addresses. Mailing addresses for organizations referenced...

  4. Clinical Semiotics

    ERIC Educational Resources Information Center

    Shands, Harley C.; Meltzer, James D.

    1975-01-01

    Clinical semiotics is defined and discussed as the discipline having to do with the interrelation between specifically human methods of communicating and processing information and specifically human psychiatric and psychosomatic disorders. (Author/RM)

  5. Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers

    PubMed Central

    Antonarakis, Emmanuel S.; Heath, Elisabeth I.; Walczak, Janet R.; Nelson, William G.; Fedor, Helen; De Marzo, Angelo M.; Zahurak, Marianna L.; Piantadosi, Steven; Dannenberg, Andrew J.; Gurganus, Robin T.; Baker, Sharyn D.; Parnes, Howard L.; DeWeese, Theodore L.; Partin, Alan W.; Carducci, Michael A.

    2009-01-01

    Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum ≥ 7, prostate-specific antigen (PSA) ≥ 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies. PMID:19720908

  6. HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes

    PubMed Central

    Krishnan, Sridevi; Shimoda, Michiko; Sacchi, Romina; Kailemia, Muchena J.; Luxardi, Guillaume; Kaysen, George A.; Parikh, Atul N.; Ngassam, Viviane N.; Johansen, Kirsten; Chertow, Glenn M.; Grimes, Barbara; Smilowitz, Jennifer T.; Maverakis, Emanual; Lebrilla, Carlito B.; Zivkovic, Angela M.

    2017-01-01

    The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL’s immunomodulatory function. HDL were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) (n = 13), and diabetic hemodialysis (HD) patients (n = 24). Concentrations of HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycovariations of ApoC-III, A1AT, and A2HSG were measured. Secretion of interleukin 6 (IL-6) in lipopolysaccharide-stimulated monocytes was used as a prototypical assay of HDL’s immunomodulatory capacity. HDL from HD patients were enriched in SAA, LBP, ApoC-III, di-sialylated ApoC-III (ApoC-III2) and desialylated A2HSG. HDL that increased IL-6 secretion were enriched in ApoC-III, di-sialylated glycans at multiple A1AT glycosylation sites and desialylated A2HSG, and depleted in mono-sialylated ApoC-III (ApoC-III1). Subgroup analysis on HD patients who experienced an infectious hospitalization event within 60 days (HD+) (n = 12), vs. those with no event (HD−) (n = 12) showed that HDL from HD+ patients were enriched in SAA but had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including the site-specific glycosylation, differentiate between clinical groups, correlate with HDL’s immunomodulatory capacity, and may be predictive of HDL’s ability to protect from infection. PMID:28287093

  7. The Value of Addressing Patient Preferences.

    PubMed

    Allen, Jeff D; Stewart, Mark D; Roberts, Samantha A; Sigal, Ellen V

    2017-02-01

    Recent scientific progress is, in some cases, leading to transformative new medicines for diseases that previously had marginal or even no treatment options. This offers great promise for people affected by these diseases, but it has also placed stress on the health care system in terms of the growing cost associated with some new interventions. Effort has been taken to create tools to help patients and health care providers assess the value of new medical innovations. These tools may also provide the basis for assessing the price associated with new medical products. Given the growing expenditures in health care, value frameworks present an opportunity to evaluate new therapeutic options in the context of other treatments and potentially lead to a more economically sustainable health care system. In summary, the contribution to meaningful improvements in health outcomes is the primary focus of any assessment of the value of a new intervention. A component of such evaluations, however, should factor in timely access to new products that address an unmet medical need, as well as the magnitude of that beneficial impact. To achieve these goals, value assessment tools should allow for flexibility in clinical end points and trial designs, incorporate patient preferences, and continually evolve as new evidence, practice patterns, and medical progress advance.

  8. Development of item bank to measure deliberate self-harm behaviours: facilitating tailored scales and computer adaptive testing for specific research and clinical purposes.

    PubMed

    Latimer, Shane; Meade, Tanya; Tennant, Alan

    2014-07-30

    The purpose of this study was to investigate the application of item banking to questionnaire items intended to measure Deliberate Self-Harm (DSH) behaviours. The Rasch measurement model was used to evaluate behavioural items extracted from seven published DSH scales administered to 568 Australians aged 18-30 years (62% university students, 21% mental health patients, and 17% community members). Ninety four items were calibrated in the item bank (including 12 items with differential item functioning for gender and age). Tailored scale construction was demonstrated by extracting scales covering different combinations of DSH methods but with the same raw score for each person location on the latent DSH construct. A simulated computer adaptive test (starting with common self-harm methods to minimise presentation of extreme behaviours) demonstrated that 11 items (on average) were needed to achieve a standard error of measurement of 0.387 (corresponding to a Cronbach׳s Alpha of 0.85). This study lays the groundwork for advancing DSH measurement to an item bank approach with the flexibility to measure a specific definitional orientation (e.g., non-suicidal self-injury) or a broad continuum of self-harmful acts, as appropriate to a particular research/clinical purpose.

  9. Interstitial Perfusion Culture with Specific Soluble Factors Inhibits Type I Collagen Production from Human Osteoarthritic Chondrocytes in Clinical-Grade Collagen Sponges

    PubMed Central

    Talò, Giuseppe; Lovati, Arianna B.; Pasdeloup, Marielle; Riboldi, Stefania A.; Moretti, Matteo; Mallein-Gerin, Frédéric

    2016-01-01

    Articular cartilage has poor healing ability and cartilage injuries often evolve to osteoarthritis. Cell-based strategies aiming to engineer cartilaginous tissue through the combination of biocompatible scaffolds and articular chondrocytes represent an alternative to standard surgical techniques. In this context, perfusion bioreactors have been introduced to enhance cellular access to oxygen and nutrients, hence overcoming the limitations of static culture and improving matrix deposition. Here, we combined an optimized cocktail of soluble factors, the BIT (BMP-2, Insulin, Thyroxin), and clinical-grade collagen sponges with a bidirectional perfusion bioreactor, namely the oscillating perfusion bioreactor (OPB), to engineer in vitro articular cartilage by human articular chondrocytes (HACs) obtained from osteoarthritic patients. After amplification, HACs were seeded and cultivated in collagen sponges either in static or dynamic conditions. Chondrocyte phenotype and the nature of the matrix synthesized by HACs were assessed using western blotting and immunohistochemistry analyses. Finally, the stability of the cartilaginous tissue produced by HACs was evaluated in vivo by subcutaneous implantation in nude mice. Our results showed that perfusion improved the distribution and quality of cartilaginous matrix deposited within the sponges, compared to static conditions. Specifically, dynamic culture in the OPB, in combination with the BIT cocktail, resulted in the homogeneous production of extracellular matrix rich in type II collagen. Remarkably, the production of type I collagen, a marker of fibrous tissues, was also inhibited, indicating that the association of the OPB with the BIT cocktail limits fibrocartilage formation, favoring the reconstruction of hyaline cartilage. PMID:27584727

  10. The evaluation of histo-blood group ABO typing by flow cytometric and PCR-amplification of specific alleles analyses and their application in clinical laboratories.

    PubMed

    Aki, Kensaku; Izumi, Azusa; Hosoi, Eiji

    2012-01-01

    ABO antigens are oligosaccharide antigens, and are widely distributed on red blood and tissue cells as well as in saliva and body fluid. Therefore, these antigens are important not only for blood transfusion, but also for tissue cell and organ transplantations. Also, blood, hair, and seminal fluid are important sources of evidence at crime scenes, and these antigens are some of the most important markers for personal identification in forensic investigations. Here, we describe the development and use of quantitative analysis of A, B, and H antigens on red blood cells by employing flow cytometric analysis and the ABO genotyping method based on PCR-amplification of specific alleles (PASA) within DNA, especially from blood and saliva. In this study, flow cytometric analysis could be used to compare the differences between the expression of A and/or B and H antigens on red blood cells with various phenotypes, and the PASA method was able to determine the genotype of the type cisA(2)B(3) pedigree using only DNA extracted from saliva. These analysis methods are simple and useful for judging the ABO blood group system and genotyping, and are used widely throughout research and clinical laboratories and forensic fields.

  11. TH-A-BRF-10: Quantification of Subject-Specific Susceptibility-Related Geometric Distortion in Clinical Liver MRI for Radiation Therapy

    SciTech Connect

    Zhu, T; Matakos, A; Feng, M; Lawrence, T; Cao, Y

    2014-06-15

    Purpose: Subject-specific susceptibility-induced B0 inhomogeneity affects the geometric accuracy of MRI images, with potential impact on the accuracy of treatment planning and image guidance. This study quantifies individual distortions for patients with intrahepatic tumors. Methods: Liver MRI scans of 13 patients who were enrolled in an IRB approved study were acquired on a 3T scanner (Skyra, Siemens). Clinical contrast-enhanced images were acquired by a 3D Volume Interpolated Breath-Hold Examination (VIBE) sequence with TE/TR =1.65/4.3ms, voxel size = 2.5×2.5×3mm (axial sets) or 3.5×3.5×5mm (coronal sets), and frequency-encoding (FE) bandwidth of 440Hz/pixel. B0 inhomogeneity was evaluated by acquisition of dual gradient echoes (GRE) with TE1/TE2/TR =4.92/7.38/106ms, a voxel size of 3.5×3.5×3.75mm, a FE bandwidth of 290Hz/pixel and breath-hold. The phase difference maps from the two echoes were unwrapped using a quantitative MRI analysis software package (FSL, FMRIB, Oxford, UK). The resulting calculated B0 inhomogeneity maps (ΔB0 in Hz) were converted to voxel distortion maps in the FE direction (ΔX in mm) corresponding to the VIBE images. Results: Maximum susceptibility-induced distortions were observed in the liver dome near the diaphragm. Using results from coronal VIBE images in this study as examples, we observed clusters of voxels displaced close to or greater than ΔX=3.5mm (440 Hz in ΔB0) in the VIBE images of the liver in 3 patients, and greater than 2 mm but less than 3.5 mm in 12 patients. On average, approximately 14% of imaged liver voxels had distortions ΔX>±1mm (ΔB0>±125Hz) and 1% of the voxels had ΔX>±2mm (ΔB0>±250Hz). Conclusion: Although advanced MRI techniques, like VIBE, permit faster acquisitions allowing for breath-held examinations with limited motion-induced artifacts, this study suggests that localized distortions due to subject-specific susceptibility variations can occur and require additional advanced corrections

  12. [Antifungal susceptibility profiles of Candida species to triazole: application of new CLSI species-specific clinical breakpoints and epidemiological cutoff values for characterization of antifungal resistance].

    PubMed

    Karabıçak, Nilgün; Alem, Nihal

    2016-01-01

    The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antifungal Susceptibility Testing has newly introduced species-specific clinical breakpoints (CBPs) for fluconazole and voriconazole. When CBPs can not be determined, wild-type minimal inhibitory concentration (MIC) distributions are detected and epidemiological cutoff values (ECVs) provide valuable means for the detection of emerging resistance. The aim of this study is to determine triazole resistance patterns in Candida species by the recently revised CLSI CBPs. A total of 140 Candida strains isolated from blood cultures of patients with invasive candidiasis hospitalized in various intensive care units in Turkey and sent to our reference laboratory between 2011-2012, were included in the study. The isolates were identified by conventional methods, and susceptibility testing was performed against fluconazole, itraconazole and voriconazole, by the 24-h CLSI broth microdilution (BMD) method. Azole resistance rates for all Candida species were determined using the new species-specific CLSI CBPs and ECVs criteria, when appropriate. The species distribution of the isolates were as follows; C.parapsilosis (n= 31 ), C.tropicalis (n= 26 ), C.glabrata (n= 21), C.albicans (n= 18), C.lusitaniae (n= 16), C.krusei (n= 16), C.kefyr (n= 9), C.guilliermondii (n= 2), and C.dubliniensis (n= 1). According to the newly determined CLSI CBPs for fluconazole and C.albicans, C.parapsilosis, C.tropicalis [susceptible (S), ≤ 2 µg/ml; dose-dependent susceptible (SDD), 4 µg/ml; resistant (R), ≥ 8 µg/ml], and C.glabrata (SDD, ≤ 32 µg/ml; R≥ 64 µg/ml) and for voriconazole and C.albicans, C.parapsilosis, C.tropicalis (S, ≤ 0.12 µg/ml; SDD, 0.25-0.5 µg/ml; R, ≥ 1 µg/ml), and C.krusei (S, ≤ 0.5 µg/ml; SDD, 1 µg/ml; R, ≥ 2 µg/ml), it was found that three of C.albicans, one of C.parapsilosis and one of C.glabrata isolates were resistant to fluconazole, while two of C.albicans and two of C

  13. Non-specific low back pain in primary care in the Spanish National Health Service: a prospective study on clinical outcomes and determinants of management

    PubMed Central

    Kovacs, Francisco M; Fernández, Carmen; Cordero, Antonio; Muriel, Alfonso; González-Luján, Luis; Gil del Real, María Teresa

    2006-01-01

    Background The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months. Methods A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave. Results Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and

  14. An addressable cell array for a platform of biosensor chips

    NASA Astrophysics Data System (ADS)

    Yang, Seungkyoung; Choi, Soo-hee; Jung, Moon Youn; Song, Kibong; Park, Jeong Won

    2013-05-01

    In order to detect interested matters in fields, various lab-on-a-chips where chemical, physical, or biological sensors are loaded have been developed. eNOSE can be a representative example among them. Because animals can sense 300~1000 different chemicals by olfactory system - smell -, the olfactory system has been spotlighted as new materials in the field of sensing. Those investigations, however, are usually focused on how to detect signals from the olfactory neurons or receptors loaded on chips and enhance sensing efficacy of chips. Therefore, almost of those chips are designed for only one material sensing. Multi-sensing using multi-channels will be needed when the olfactory systems are adopted well on chips. For multiple sensing, we developed an addressable cell array. The chip has 38 cell-chambers arranged in a circle shape and different cell types of thirty eight can be allocated with specific addresses on the chip without any complex valve system. In order to confirm the cell addressing, we loaded EGFP-transfected and empty vector-transfected HEK293a cells into inlets of the cell array in a planned address and those cells were positioned into each chamber by brief aspiration. The arrayed cells were confirmed as a specific pattern through EGFP and nuclei staining. This cell array which can generate address of sensor materials like cells with their own specification is expected to be applied to a platform for a biosensor chip at various sensing fields.

  15. IPv6 Addressing Proxy: Mapping Native Addressing from Legacy Technologies and Devices to the Internet of Things (IPv6)

    PubMed Central

    Jara, Antonio J.; Moreno-Sanchez, Pedro; Skarmeta, Antonio F.; Varakliotis, Socrates; Kirstein, Peter

    2013-01-01

    Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT). IPv6 provides addressing space to reach this ubiquitous set of sensors, but legacy technologies, such as X10, European Installation Bus (EIB), Controller Area Network (CAN) and radio frequency ID (RFID) from the industrial, home automation and logistic application areas, do not support the IPv6 protocol. For that reason, a technique must be devised to map the sensor and identification technologies to IPv6, thus allowing homogeneous access via IPv6 features in the context of the IoT. This paper proposes a mapping between the native addressing of each technology and an IPv6 address following a set of rules that are discussed and proposed in this work. Specifically, the paper presents a technology-dependent IPv6 addressing proxy, which maps each device to the different subnetworks built under the IPv6 prefix addresses provided by the internet service provider for each home, building or user. The IPv6 addressing proxy offers a common addressing environment based on IPv6 for all the devices, regardless of the device technology. Thereby, this offers a scalable and homogeneous solution to interact with devices that do not support IPv6 addressing. The IPv6 addressing proxy has been implemented in a multi-protocol card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6. PMID:23686145

  16. IPv6 addressing proxy: mapping native addressing from legacy technologies and devices to the Internet of Things (IPv6).

    PubMed

    Jara, Antonio J; Moreno-Sanchez, Pedro; Skarmeta, Antonio F; Varakliotis, Socrates; Kirstein, Peter

    2013-05-17

    Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT). IPv6 provides addressing space to reach this ubiquitous set of sensors, but legacy technologies, such as X10, European Installation Bus (EIB), Controller Area Network (CAN) and radio frequency ID (RFID) from the industrial, home automation and logistic application areas, do not support the IPv6 protocol. For that reason, a technique must be devised to map the sensor and identification technologies to IPv6, thus allowing homogeneous access via IPv6 features in the context of the IoT. This paper proposes a mapping between the native addressing of each technology and an IPv6 address following a set of rules that are discussed and proposed in this work. Specifically, the paper presents a technology-dependent IPv6 addressing proxy, which maps each device to the different subnetworks built under the IPv6 prefix addresses provided by the internet service provider for each home, building or user. The IPv6 addressing proxy offers a common addressing environment based on IPv6 for all the devices, regardless of the device technology. Thereby, this offers a scalable and homogeneous solution to interact with devices that do not support IPv6 addressing. The IPv6 addressing proxy has been implemented in a multi-protocol Sensors 2013, 13 6688 card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6.

  17. Scaffold Translation: Barriers Between Concept and Clinic

    PubMed Central

    Murphy, William L.

    2011-01-01

    Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical use remains, bluntly, a failure. This dearth of translated tissue engineering therapies (including scaffolds) remains despite 25 years of research, research funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search). Enabling scaffold translation requires first an understanding of the challenges, and second, addressing the complete range of these challenges. There are the obvious technical challenges of designing, manufacturing, and functionalizing scaffolds to fill the Form, Fixation, Function, and Formation needs of bone defect repair. However, these technical solutions should be targeted to specific clinical indications (e.g., mandibular defects, spine fusion, long bone defects, etc.). Further, technical solutions should also address business challenges, including the need to obtain regulatory approval, meet specific market needs, and obtain private investment to develop products, again for specific clinical indications. Finally, these business and technical challenges present a much different model than the typical research paradigm, presenting the field with philosophical challenges in terms of publishing and funding priorities that should be addressed as well. In this article, we review in detail the technical, business, and philosophical barriers of translating scaffolds from Concept to Clinic. We argue that envisioning and engineering scaffolds as modular systems with a sliding scale of complexity offers the best path to addressing these translational challenges. PMID:21902613

  18. Assessing what to address in science communication

    PubMed Central

    Bruine de Bruin, Wändi; Bostrom, Ann

    2013-01-01

    As members of a democratic society, individuals face complex decisions about whether to support climate change mitigation, vaccinations, genetically modified food, nanotechnology, geoengineering, and so on. To inform people’s decisions and public debate, scientific experts at government agencies, nongovernmental organizations, and other organizations aim to provide understandable and scientifically accurate communication materials. Such communications aim to improve people’s understanding of the decision-relevant issues, and if needed, promote behavior change. Unfortunately, existing communications sometimes fail when scientific experts lack information about what people need to know to make more informed decisions or what wording people use to describe relevant concepts. We provide an introduction for scientific experts about how to use mental models research with intended audience members to inform their communication efforts. Specifically, we describe how to conduct interviews to characterize people’s decision-relevant beliefs or mental models of the topic under consideration, identify gaps and misconceptions in their knowledge, and reveal their preferred wording. We also describe methods for designing follow-up surveys with larger samples to examine the prevalence of beliefs as well as the relationships of beliefs with behaviors. Finally, we discuss how findings from these interviews and surveys can be used to design communications that effectively address gaps and misconceptions in people’s mental models in wording that they understand. We present applications to different scientific domains, showing that this approach leads to communications that improve recipients’ understanding and ability to make informed decisions. PMID:23942122

  19. Assessing what to address in science communication.

    PubMed

    Bruine de Bruin, Wändi; Bostrom, Ann

    2013-08-20

    As members of a democratic society, individuals face complex decisions about whether to support climate change mitigation, vaccinations, genetically modified food, nanotechnology, geoengineering, and so on. To inform people's decisions and public debate, scientific experts at government agencies, nongovernmental organizations, and other organizations aim to provide understandable and scientifically accurate communication materials. Such communications aim to improve people's understanding of the decision-relevant issues, and if needed, promote behavior change. Unfortunately, existing communications sometimes fail when scientific experts lack information about what people need to know to make more informed decisions or what wording people use to describe relevant concepts. We provide an introduction for scientific experts about how to use mental models research with intended audience members to inform their communication efforts. Specifically, we describe how to conduct interviews to characterize people's decision-relevant beliefs or mental models of the topic under consideration, identify gaps and misconceptions in their knowledge, and reveal their preferred wording. We also describe methods for designing follow-up surveys with larger samples to examine the prevalence of beliefs as well as the relationships of beliefs with behaviors. Finally, we discuss how findings from these interviews and surveys can be used to design communications that effectively address gaps and misconceptions in people's mental models in wording that they understand. We present applications to different scientific domains, showing that this approach leads to communications that improve recipients' understanding and ability to make informed decisions.

  20. Addressing Cultural and Native Language Interference in Second Language Acquisition

    ERIC Educational Resources Information Center

    Allard, Daniele; Bourdeau, Jacqueline; Mizoguchi, Riichiro

    2011-01-01

    This paper addresses the problem of cultural and native language interference in second/foreign language acquisition. More specifically, it examines issues of interference that can be traced to a student's native language and that also have a cultural component. To this effect, an understanding of what actually comprises both interference and…

  1. Designing Interactive Multimedia Instruction to Address Soldiers’ Learning Needs

    DTIC Science & Technology

    2014-12-01

    learners’ experiences , background knowledge, and job-specific requirements. Here, we describe the process used and rationale for our approach to...According to Clark and Mayer (2008), these critical design features address three goals: (a) reducing extrinsic cognitive processing , (b) managing...intrinsic cognitive processing , and (c) facilitating generative processing . Table 5 summarizes the features of well-designed IMI identified by Mayer

  2. Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

    PubMed Central

    Cofield, Stacey; Conwit, Robin; Barsan, William; Quinn, James

    2010-01-01

    The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in emergency medicine clinical trials. PMID:21040112

  3. Production of high specific activity (195m) Pt-cisplatinum at South African Nuclear Energy Corporation for Phase 0 clinical trials in healthy individual subjects.

    PubMed

    Zeevaart, Jan Rijn; Wagener, Judith; Marjanovic-Painter, Biljana; Sathekge, Mike; Soni, Nischal; Zinn, Christa; Perkins, Gary; Smith, Suzanne V

    2013-01-01

    Platinum agents continue to be the main chemotherapeutic agents used in the first-line and second-line treatments of cancer patients. It is important to fully understand the biological profile of these compounds in order to optimize the dose given to each patient. In a joint project with the Australian Nuclear Science and Technology Organisation and the Nuclear Medicine Department at Steve Biko Academic Hospital, South African Nuclear Energy Corporation synthesized and supplied (195m) Pt-cisplatinum (commonly referred to as cisplatin) for a clinical pilot study on healthy volunteers. Enriched (194) PtCl2 was prepared by digestion of enriched (194) Pt metal (>95%) followed by thermal decomposition over a 3 h period. The (194) PtCl2 was then placed in a quartz ampoule, was irradiated in SAFARI-1 up to 200 h, then decay cooled for a minimum of 34 h prior to synthesis of final product. (195m) Pt(NH3 )2 I2 , formed with the addition of KI and NH4 OH, was converted to the diaqua species [(195m) Pt(NH3 )2 (H2 O)2 ](2+) by reaction with AgNO3 . The conversion to (195m) Pt-cisplatinum was completed by the addition of concentrated HCl. The final product yield was 51.7% ± 5.2% (n = 5). The chemical and radionuclidic purity in each case was >95%. The use of a high flux reactor position affords a higher specific activity product (15.9 ± 2.5 MBq/mg at end of synthesis) than previously found (5 MBq/mg). Volunteers received between 108 and 126 MBq of radioactivity, which is equivalent to 6.8-10.0 mg of carrier cisplatinum. Such high specific activities afforded a significant reduction (~50%) in the chemical dose of a carrier cisplatinum, which represents less than 10% of a typical chemotherapeutic dose given to patients. A good manufacturing practice GMP compliant product was produced and was administered to 10 healthy volunteers as part of an ethically approved Phase 0 clinical trial. The majority of the injected activity 27.5% ± 5.8% was excreted

  4. Evaluation of species-specific PCR, Bruker MS, VITEK MS and the VITEK 2 system for the identification of clinical Enterococcus isolates.

    PubMed

    Fang, H; Ohlsson, A-K; Ullberg, M; Ozenci, V

    2012-11-01

    The purpose of this investigation was to compare the performance of species-specific polymerase chain reaction (PCR), matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and phenotypic identification systems for the identification of Enterococcus species. A total of 132 clinical isolates were investigated by the following: (1) a multiplex real-time PCR assay targeting ddl Enterococcus faecium, ddl Enterococcus faecalis, vanC1 and vanC2/C3 genes, and a high-resolution melting (HRM) analysis of the groESL gene for the differentiation of Enterococcus casseliflavus and Enterococcus gallinarum; (2) Bruker MS; (3) VITEK MS; and (4) the VITEK 2 system. 16S rRNA gene sequencing was used as a reference method in the study. The 132 isolates were identified as 32 E. faecalis, 63 E. faecium, 16 E. casseliflavus and 21 E. gallinarum. The multiplex PCR, Bruker MS and VITEK MS were able to identify all the isolates correctly at the species level. The VITEK 2 system could identify 131/132 (99.2 %) and 121/132 (91.7 %) of the isolates at the genus and species levels, respectively. The HRM-groESL assay identified all (21/21) E. gallinarum isolates and 81.3 % (13/16) of the E. casseliflavus isolates. The PCR methods described in the present study are effective in identifying the enterococcal species. MALDI-TOF MS is a rapid, reliable and cost-effective identification technique for enterococci. The VITEK 2 system is less efficient at detecting non-faecalis and non-faecium Enterococcus species.

  5. Clinical profile, species-specific severity grading, and outcome determinants of snake envenomation: An Indian tertiary care hospital-based prospective study

    PubMed Central

    Saravu, Kavitha; Somavarapu, Vasanth; Shastry, Ananthkrishna B.; Kumar, Rishikesh

    2012-01-01

    Objective: We undertook this study to assess the clinical profile and outcome determinants of different snake envenomation as well as to assign species-specific severity grade to different cases based on clinico – laboratory evidence scale. Materials and Methods: A prospective clinico – epidemiologic evaluation for outcome determinants of snakebite envenomation was carried out based on a clinico – laboratory severity grading scale, among 76 patients over a period of 2 years, in a tertiary care hospital in southern India. Results: Majority of patients were male agricultural workers (53.9%) followed by housewives (19.7%), and students (9.2%). Occurrence of viper snake envenomation with hemotoxic syndrome (73.68%) was highest followed by cobra and krait envenomation with neurotoxic (19.73%) and hemo – neurotoxic (5.3%) syndrome, respectively. On the contrary, maximum mortality and severity was seen in krait (60%) followed by cobra (13.33%) and viper (8.9%) envenomation. The average dose of anti-snake venom (ASV) administered varied from 9.83 (±7.22) to 20.25 (±4.92) vials throughout grade I to IV in all snake species envenomation. An increase in severity grade, ASV dose, and mortality were observed with the corresponding delay in ‘bite to needle time.’ Also, initial traditional treatments and krait species envenomation were significantly associated with higher grades of severity and mortality. Conclusion: There is an urgent need to spread awareness among the community for avoidance of traditional treatment and any delay in medical intervention in snakebite incidents. PMID:23559724

  6. The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients With Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial

    PubMed Central

    Shahrokhi, Nader; Soltani, Zahra; Khaksari, Mohammad; Karamouzian, Saeid; Mofid, Behshad; Asadikaram, Gholamreza

    2016-01-01

    Background Improvement of neurologic outcome in progesterone-administered patients with diffuse axonal injury (DAI) has been found in a recent study. Also, there has been interest in the importance of serum parameters as predictors of outcome in traumatic brain injury. Objectives The aim of this study was to examine the effect of progesterone administration on serum levels of neuron-specific enolase (NSE), and intercellular adhesion molecule-1 (ICAM-1) in clinical DAI. Patients and Methods In this study, the serum levels of ICAM-1 and NSE of 32 male DAI patients (18 - 60 years of age, a Glasgow coma scale of 12 or less, and admitted within 4 hours after injury) who were randomized for a controlled phase II trial of progesterone were analyzed. The analysis was performed between the control and progesterone groups at admission time, and 24 hours and six days after DAI, respectively. Results A reduction in the serum level of ICAM-1 was noticed in the progesterone group 24 hours after the injury (P < 0.05). There was no significant difference in the serum level of NSE between the study groups during evaluation. At 24 hours after the injury, the level of ICAM-1 in the control group was higher than that at admission time (P < 0.05). The lowest level of NSE in the two groups was seen six days after DAI (P < 0.01). Conclusions In summary, progesterone administration reduced serum ICAM-1, and whereby may attenuate blood brain barrier disruption, the latter needs further investigation for confirmation. PMID:27800469

  7. Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

    PubMed

    Catalona, William J; Richie, Jerome P; Ahmann, Frederick R; Hudson, M'Liss A; Scardino, Peter T; Flanigan, Robert C; DeKernion, Jean B; Ratliff, Timothy L; Kavoussi, Louis R; Dalkin, Bruce L; Waters, W Bedford; MacFarlane, Michael T; Southwick, Paula C

    2017-02-01

    To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 μg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 μg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

  8. Novel Duplicate Address Detection with Hash Function

    PubMed Central

    Song, GuangJia; Ji, ZhenZhou

    2016-01-01

    Duplicate address detection (DAD) is an important component of the address resolution protocol (ARP) and the neighbor discovery protocol (NDP). DAD determines whether an IP address is in conflict with other nodes. In traditional DAD, the target address to be detected is broadcast through the network, which provides convenience for malicious nodes to attack. A malicious node can send a spoofing reply to prevent the address configuration of a normal node, and thus, a denial-of-service attack is launched. This study proposes a hash method to hide the target address in DAD, which prevents an attack node from launching destination attacks. If the address of a normal node is identical to the detection address, then its hash value should be the same as the “Hash_64” field in the neighboring solicitation message. Consequently, DAD can be successfully completed. This process is called DAD-h. Simulation results indicate that address configuration using DAD-h has a considerably higher success rate when under attack compared with traditional DAD. Comparative analysis shows that DAD-h does not require third-party devices and considerable computing resources; it also provides a lightweight security resolution. PMID:26991901

  9. 49 CFR 1102.1 - How addressed.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false How addressed. 1102.1 Section 1102.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE COMMUNICATIONS § 1102.1 How addressed. All communications...

  10. 49 CFR 1102.1 - How addressed.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 8 2013-10-01 2013-10-01 false How addressed. 1102.1 Section 1102.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE COMMUNICATIONS § 1102.1 How addressed. All communications...

  11. 49 CFR 1102.1 - How addressed.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 8 2014-10-01 2014-10-01 false How addressed. 1102.1 Section 1102.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE COMMUNICATIONS § 1102.1 How addressed. All communications...

  12. 49 CFR 1102.1 - How addressed.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 8 2012-10-01 2012-10-01 false How addressed. 1102.1 Section 1102.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE COMMUNICATIONS § 1102.1 How addressed. All communications...

  13. 49 CFR 1102.1 - How addressed.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 8 2011-10-01 2011-10-01 false How addressed. 1102.1 Section 1102.1 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE COMMUNICATIONS § 1102.1 How addressed. All communications...

  14. 49 CFR 369.6 - Address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS REPORTS OF MOTOR CARRIERS § 369.6 Address. The following address must be used by motor carriers when submitting a report, requesting an exemption from filing...

  15. Approaches for Resolving Dynamic IP Addressing.

    ERIC Educational Resources Information Center

    Foo, Schubert; Hui, Siu Cheung; Yip, See Wai; He, Yulan

    1997-01-01

    A problem with dynamic Internet protocol (IP) addressing arises when the Internet connection is through an Internet provider since the IP address is allocated only at connection time. This article examines a number of online and offline methods for resolving the problem. Suggests dynamic domain name system (DNS) and directory service look-up are…

  16. 37 CFR 41.10 - Correspondence addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Correspondence addresses. 41....10 Correspondence addresses. Except as the Board may otherwise direct, (a) Appeals. Correspondence in... all other correspondence in an application or a patent involved in an appeal to the Board for which...

  17. 37 CFR 41.10 - Correspondence addresses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Correspondence addresses. 41....10 Correspondence addresses. Except as the Board may otherwise direct, (a) Appeals. Correspondence in... all other correspondence in an application or a patent involved in an appeal to the Board for which...

  18. 37 CFR 41.10 - Correspondence addresses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Correspondence addresses. 41....10 Correspondence addresses. Except as the Board may otherwise direct, (a) Appeals. Correspondence in... all other correspondence in an application or a patent involved in an appeal to the Board for which...

  19. History Forum Addresses Creation/Evolution Controversy.

    ERIC Educational Resources Information Center

    Schweinsberg, John

    1997-01-01

    A series of programs entitled Creationism and Evolution: The History of a Controversy was presented at the University of Alabama in Huntsville. The controversy was addressed from an historical and sociological, rather than a scientific perspective. Speakers addressed the evolution of scientific creationism, ancient texts versus sedimentary rocks…

  20. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Address searches. 674.44 Section 674.44 Education..., DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If mail... litigation; (2) The account is assigned to the United States; or (3) The account is written off under §...

  1. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false Address searches. 674.44 Section 674.44 Education..., DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If mail... litigation; (2) The account is assigned to the United States; or (3) The account is written off under §...

  2. Forms of Address in Chilean Spanish

    ERIC Educational Resources Information Center

    Bishop, Kelley; Michnowicz, Jim

    2010-01-01

    The present investigation examines possible social and linguistic factors that influence forms of address used in Chilean Spanish with various interlocutors. A characteristic of the Spanish of Chile is the use of a variety of forms of address for the second person singular, "tu", "vos", and "usted", with corresponding…

  3. Image compression using address-vector quantization

    NASA Astrophysics Data System (ADS)

    Nasrabadi, Nasser M.; Feng, Yushu

    1990-12-01

    A novel vector quantization scheme, the address-vector quantizer (A-VQ), is proposed which exploits the interblock correlation by encoding a group of blocks together using an address-codebook (AC). The AC is a set of address-codevectors (ACVs), each representing a combination of addresses or indices. Each element of the ACV is an address of an entry in the LBG-codebook, representing a vector-quantized block. The AC consists of an active (addressable) region and an inactive (nonaddressable) region. During encoding the ACVs in the AC are reordered adaptively to bring the most probable ACVs into the active region. When encoding an ACV, the active region is checked, and if such an address combination exists, its index is transmitted to the receiver. Otherwise, the address of each block is transmitted individually. The SNR of the images encoded by the A-VQ method is the same as that of a memoryless vector quantizer, but the bit rate is by a factor of approximately two.

  4. Science, technology, and innovation: nursing responsibilities in clinical research.

    PubMed

    Grady, Christine; Edgerly, Maureen

    2009-12-01

    Clinical research is a systematic investigation of human biology, health, or illness involving human beings. It builds on laboratory and animal studies and often involves clinical trials, which are specifically designed to test the safety and efficacy of interventions in humans. Nurses are critical to the conduct of ethical clinical research and face clinical, ethical, and regulatory challenges in research in many diverse roles. Understanding and addressing the ethical challenges that complicate clinical research is integral to upholding the moral commitment that nurses make to patients, including protecting their rights and ensuring their safety as patients and as research participants.

  5. Addressing Disparities in Sudden Cardiac Arrest Care and the Under-Utilization of Effective Therapies

    PubMed Central

    Kong, Melissa H.; Peterson, Eric D.; Fonarow, Gregg C.; Sanders, Gillian D.; Yancy, Clyde W.; Russo, Andrea M.; Curtis, Anne B.; Sears, Samuel F.; Thomas, Kevin L.; Campbell, Susan; Carlson, Mark D.; Chiames, Chris; Cook, Nakela L.; Hayes, David L.; LaRue, Michelle; Hernandez, Adrian F.; Lyons, Edward L.; Al-Khatib, Sana M.

    2010-01-01

    Sudden cardiac arrest (SCA) is the most common cause of death in the Unites States. Despite its major impact on public health, significant challenges exist at the patient, provider, public, and policy levels with respect to raising more widespread awareness and understanding of SCA risks, identifying patients at risk for SCA, addressing barriers to SCA care, and eliminating disparities in SCA care and outcomes. To address many of these challenges, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) held a think tank meeting on December 7, 2009, convening experts on this issue from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers. The specific goals of the meeting were to examine existing educational tools on SCA for patients, health care providers and the public and explore ways to enhance and disseminate these tools, to propose a framework for improved identification of patients at risk of SCA, and to review the latest data on disparities in SCA care and explore ways to reduce these disparities. This paper summarizes the discussions that occurred at the meeting. PMID:20934553

  6. SU-E-T-532: Validation and Implementation of Model-Based Patient Specific Quality Assurance Using Mobius3D and MobiusFX in a Clinical Setting

    SciTech Connect

    Galavis, P; Osterman, K; Jozsef, G; Becker, S; Dewyngaert, K

    2014-06-01

    Purpose: This work carries out the commissioning and validation of the Mobius3D and MobiusFX software tools, which can replace the time-consuming measurement-based patient specific quality assurance (PSQA). Methods: The beam model supplied by Mobius3D was validated against a 21EX linac's beam measured data. Complex patient (VMAT) plans using Eclipse treatment planning system (TPS) was used to test the consistency between Mobius3D (calculates dose using patient image and field data) and MobiusFx (calculates dose using treatment dynalog files). Dose difference and gamma analysis (3%/3mm) between Mobius3D and MobiusFx were used to assess treatment plan and treatment delivery consistency. An end-to-end test was performed to validate Mobius3D and MobiusFx against ion chamber measurements. Effect of the dosimetric leaf gap (DLG) on Mobius3D dose calculation was additionally investigated. Results: Mobius3D beam model parameters matched within 1%-3% with our beam measured data. A comparison of Mobius3D and MobiusFx dose matrices for VMAT planned prostate cases showed (0.33±0.07)% mean dose difference with gamma values above 95%. The end-to-end test showed dose differences of 1% between Mobius3D and MobiusFx. Dependence of Mobius3D dose calculation upon DLG was explored by introducing a ±0.5 mm change in the default value for DLG. This change resulted in agreement differences above 2% Conclusion: Use of reference beam data would appear to speed up commissioning process for the clinical implementation of Mobius3D. However, careful consideration is required when comparing the information provided by the software, since large dose variations can be seen when the proper parameters are not optimized. The plan and delivered dose were in good agreement; hence MobiusFx has the potential to significantly speed up the PSQA process and at the same time helps to verify treatment parameters that are not possible with measurement-based PSQA.

  7. Expression pattern of transcription factors and intracellular cytokines reveals that clinically cured tuberculosis is accompanied by an increase in Mycobacterium-specific Th1, Th2, and Th17 cells.

    PubMed

    da Silva, Marcos V; Massaro Junior, Vladimir J; Machado, Juliana R; Silva, Djalma A A; Castellano, Lúcio R; Alexandre, Patricia B D; Rodrigues, Denise B R; Rodrigues, Virmondes

    2015-01-01

    Tuberculosis (TB) remains a major global health problem and is the second biggest cause of death by infectious disease worldwide. Here, we investigate in vitro the Th1, Th2, Th17, and Treg cytokines and transcriptional factors produced after Mycobacterium-specific antigen stimulation in patients with active pulmonary tuberculosis, clinically cured pulmonary tuberculosis, and healthy donors with a positive tuberculin skin test (TST+). Together, our data indicate that clinical cure after treatment increases the percentages of Mycobacterium-specific Th1, Th2, and Th17 cells compared with those found in active-TB and TST+ healthy donors. These results show that the host-parasite equilibrium in latent TB breaks in favor of the microorganism and that the subsequent clinical recovery posttreatment does not return the percentage levels of such cells to those observed in latent tuberculosis. Additionally, our results indicate that rather than showing an increase in the percentage of Mycobacterium-specific Tregs, active-TB patients display lower Th1 : Treg and Th17 : Treg ratios. These data, together with lower Th1 : Th2 and Th17 : Th2 ratios, may indicate a mechanism by which the breakdown of the host-parasite equilibrium leads to active-TB and changes in the repertoire of Mycobacterium-specific Th cells that are associated with clinical cure after treatment of pulmonary tuberculosis.

  8. Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

    PubMed

    Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

    2014-08-01

    Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations.

  9. Addressing Your Child's Weight at the Doctor

    MedlinePlus

    ... a Healthy Heart Healthy Kids Our Kids Programs Childhood Obesity What is childhood obesity? Overweight in Children BMI in Children Is Childhood Obesity an Issue in Your Home? Addressing your Child's ...

  10. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815...

  11. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815...

  12. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815...

  13. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815...

  14. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to the Curator, ARS Patent Culture Collection, Northern Regional Research Center, USDA-ARS, 1815...

  15. 76 FR 27020 - Representative and Address Provisions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE United States Patent and Trademark Office Representative and Address Provisions ACTION: Proposed collection; comment request. SUMMARY: The United States Patent and Trademark Office (USPTO), as part of...

  16. Optical Addressing And Clocking Of RAM's

    NASA Technical Reports Server (NTRS)

    Johnston, Alan R.; Nixon, Robert H.; Bergman, Larry A.; Esener, Sadik

    1989-01-01

    Proposed random-access-memory (RAM) addressing system, in which memory linked optically to read/write logic circuits, greatly increases computer operating speed. System - comprises addressing circuits including numerous lasers as signal sources, numerous optical gates including optical detectors associated with memory cells, and holographic element to direct light signals to desired memory-cell locations - applied to high-capacity digital systems, supercomputers, and complex microcircuits.

  17. An address geocoding method for improving rural spatial information infrastructure

    NASA Astrophysics Data System (ADS)

    Pan, Yuchun; Chen, Baisong; Lu, Zhou; Li, Shuhua; Zhang, Jingbo; Zhou, Yanbing

    2009-09-01

    The transition of rural and agricultural management from divisional to integrated mode has highlighted the importance of data integration and sharing. Current data are mostly collected by specific department to satisfy their own needs and lake of considering on wider potential uses. This led to great difference in data format, semantic, and precision even in same area, which is a significant barrier for constructing an integrated rural spatial information system to support integrated management and decision-making. Considering the rural cadastral management system and postal zones, the paper designs a rural address geocoding method based on rural cadastral parcel. It puts forward a geocoding standard which consists of absolute position code, relative position code and extended code. It designs a rural geocoding database model, and addresses collection and update model. Then, based on the rural address geocoding model, it proposed a data model for rural agricultural resources management. The results show that the address coding based on postal code is stable and easy to memorize, two-dimensional coding based on the direction and distance is easy to be located and memorized, while extended code can enhance the extensibility and flexibility of address geocoding.

  18. An address geocoding method for improving rural spatial information infrastructure

    NASA Astrophysics Data System (ADS)

    Pan, Yuchun; Chen, Baisong; Lu, Zhou; Li, Shuhua; Zhang, Jingbo; Zhou, YanBing

    2010-11-01

    The transition of rural and agricultural management from divisional to integrated mode has highlighted the importance of data integration and sharing. Current data are mostly collected by specific department to satisfy their own needs and lake of considering on wider potential uses. This led to great difference in data format, semantic, and precision even in same area, which is a significant barrier for constructing an integrated rural spatial information system to support integrated management and decision-making. Considering the rural cadastral management system and postal zones, the paper designs a rural address geocoding method based on rural cadastral parcel. It puts forward a geocoding standard which consists of absolute position code, relative position code and extended code. It designs a rural geocoding database model, and addresses collection and update model. Then, based on the rural address geocoding model, it proposed a data model for rural agricultural resources management. The results show that the address coding based on postal code is stable and easy to memorize, two-dimensional coding based on the direction and distance is easy to be located and memorized, while extended code can enhance the extensibility and flexibility of address geocoding.

  19. Contextual analysis of machine-printed addresses

    NASA Astrophysics Data System (ADS)

    Cullen, Peter B.; Ho, Tin K.; Hull, Jonathan J.; Prussak, Michal; Srihari, Sargur N.

    1992-08-01

    The assignment of a nine digit ZIP Code (ZIP + 4 Code) to the digital image of a machine printed address block is a problem of central importance in automated mail sorting. This problem is especially difficult since most addresses do not contain ZIP + 4 Codes and often the information that must be read to match an address to one of the 28 million entries in the ZIP + 4 file is either erroneous, incomplete, or missing altogether. This paper discusses a system for interpreting a machine printed address and assigning a ZIP + 4 Code that uses a constraint satisfaction approach. Words in an address block are first segmented and parsed to assign probable semantic categories. Word images are then recognized by a combination of digit, character, and word recognition algorithms. The control structure uses a constraint satisfaction problem solving approach to match the recognition results to an entry in the ZIP + 4 file. It is shown how this technique can both determine correct responses as well as compensate for incomplete or erroneous information. Experimental results demonstrate the success of this system. In a recent test on over 1000 machine printed address blocks, the ZIP + 4 encode rate was over 73 percent. This compares to the success rate of current postal OCRs which is about 45 percent. Additionally, the word recognition algorithm recognizes over 92 percent of the input images (over 98 percent in the top 10 choices.

  20. Rapid detection and identification of Candida albicans and Torulopsis (Candida) glabrata in clinical specimens by species-specific nested PCR amplification of a cytochrome P-450 lanosterol-alpha-demethylase (L1A1) gene fragment.

    PubMed Central

    Burgener-Kairuz, P; Zuber, J P; Jaunin, P; Buchman, T G; Bille, J; Rossier, M

    1994-01-01

    PCR of a Candida albicans cytochrome P-450 lanosterol-alpha-demethylase (P450-L1A1) gene segment is a rapid and sensitive method of detection in clinical specimens. This enzyme is a target for azole antifungal action. In order to directly detect and identify the clinically most important species of Candida, we cloned and sequenced 1.3-kbp fragments of the cytochrome P450-L1A1 genes from Torulopsis (Candida) glabrata and from Candida krusei. These segments were compared with the published sequences from C. albicans and Candida tropicalis. Amplimers for gene sequences highly conserved throughout the fungal kingdom were first used; positive PCR results were obtained for C. albicans, T. glabrata, C. krusei, Candida parapsilosis, C. tropicalis, Cryptococcus neoformans, and Trichosporon beigelii DNA extracts. Primers were then selected for a highly variable region of the gene, allowing the species-specific detection from purified DNA of C. albicans, T. glabrata, C. krusei, and C. tropicalis. The assay sensitivity as tested for C. albicans in seeded clinical specimens such as blood, peritoneal fluid, or urine was 10 to 20 cells per 0.1 ml. Compared with results obtained by culture, the sensitivity, specificity, and efficiency of the species-specific nested PCR tested with 80 clinical specimens were 71, 95, and 83% for C. albicans and 100, 97, and 98% for T. glabrata, respectively. Images PMID:7989540

  1. Interventions to address the academic impairment of children and adolescents with ADHD.

    PubMed

    Raggi, Veronica L; Chronis, Andrea M

    2006-06-01

    There exists a strong link between ADHD and academic underachievement. Both the core behavioral symptoms of ADHD and associated executive functioning deficits likely contribute to academic impairment. Current evidence-based approaches to the treatment of ADHD (i.e., stimulant medication, clinical behavior therapy and classroom behavioral interventions) have demonstrated a robust impact on behavioral variables such as attention and disruptive behavior within classroom analogue settings; however, their efficacy in improving academic outcomes is much less clear. Although surprisingly few treatment outcome studies of ADHD have attempted to incorporate interventions that specifically target academic outcomes, the studies that are available suggest that these interventions may be beneficial. The state of the treatment literature for addressing academic impairment in children and adolescents with ADHD will be reviewed herein, as well as limitations of current research, and directions for future research.

  2. Teaching undergraduate nursing students about environmental health: addressing public health issues through simulation.

    PubMed

    Stanley, Mary Jo; Rojas, Deb

    2014-01-01

    Schools of nursing are challenged to find clinical placements in public health settings. Use of simulation can address situations unique to public health, with attention to specific concerns, such as environmental health. Environmental health is an integral part of public health nursing and is a standard of professional practice. Current simulations focus on acute care situations, offering limited scenarios with a public health perspective and excluding environmental health. This study's simulation scenario was created to enhance nursing students' understanding of public health concepts within an environmental health context. Outcomes from the simulation include the need for integration of environmental issues in public health teaching. Students stated that this scenario provided a broader understanding of the environmental influences that can affect the client's and family's health. This scenario fills a void in simulation content, while providing an interactive teaching and learning strategy to help students to apply knowledge to practice.

  3. Judgments of Omitted BE and DO in Questions as Extended Finiteness Clinical Markers of Specific Language Impairment (SLI) to 15 Years: A Study of Growth and Asymptote

    ERIC Educational Resources Information Center

    Rice, Mabel L.; Hoffman, Lesa; Wexler, Ken

    2009-01-01

    Purpose: Clinical grammar markers are needed for children with SLI older than 8 years. This study followed children who were previously studied on sentences with omitted finiteness to determine if affected children continue to perform at low levels and to examine possible predictors of low performance. This is the first longitudinal report of…

  4. Addressing phenoconversion: the Achilles' heel of personalized medicine

    PubMed Central

    Shah, Rashmi R; Smith, Robert L

    2015-01-01

    Phenoconversion is a phenomenon that converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, thereby modifying their clinical response to that of genotypic PMs. Phenoconversion, usually resulting from nongenetic extrinsic factors, has a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies and personalizing therapy in routine clinical practice. The high phenotypic variability or genotype–phenotype mismatch, frequently observed due to phenoconversion within the genotypic EM population, means that the real number of phenotypic PM subjects may be greater than predicted from their genotype alone, because many genotypic EMs would be phenotypically PMs. If the phenoconverted population with genotype–phenotype mismatch, most extensively studied for CYP2D6, is as large as the evidence suggests, there is a real risk that genotype-focused association studies, typically correlating only the genotype with clinical outcomes, may miss clinically strong pharmacogenetic associations, thus compromising any potential for advancing the prospects of personalized medicine. This review focuses primarily on co-medication-induced phenoconversion and discusses potential approaches to rectify some of the current shortcomings. It advocates routine phenotyping of subjects in genotype-focused association studies and proposes a new nomenclature to categorize study populations. Even with strong and reliable data associating patients' genotypes with clinical outcome(s), there are problems clinically in applying this knowledge into routine pharmacotherapy because of potential genotype–phenotype mismatch. Drug-induced phenoconversion during routine clinical practice remains a major public health issue. Therefore, the principal challenges facing personalized medicine, which need to be addressed, include identification of the following factors: (i) drugs that are susceptible to phenoconversion

  5. Frequency addressable beams for land mobile communications

    NASA Technical Reports Server (NTRS)

    Thompson, J. D.; Dubellay, G. G.

    1988-01-01

    Satellites used for mobile communications need to serve large numbers of small, low cost terminals. The most important parameters affecting the capacity of such systems are the satellite equivalent isotropically radiated power (EIRP) and gain to noise temperature ratio (G/T) and available bandwidth. Satellites using frequency addressed beams provide high EIRP and G/T with high-gain antenna beams that also permit frequency reuse over the composite coverage area. Frequency addressing is easy to implement and compatible with low-cost terminals and offers higher capacity than alternative approaches.

  6. Shared address collectives using counter mechanisms

    DOEpatents

    Blocksome, Michael; Dozsa, Gabor; Gooding, Thomas M; Heidelberger, Philip; Kumar, Sameer; Mamidala, Amith R; Miller, Douglas

    2014-02-18

    A shared address space on a compute node stores data received from a network and data to transmit to the network. The shared address space includes an application buffer that can be directly operated upon by a plurality of processes, for instance, running on different cores on the compute node. A shared counter is used for one or more of signaling arrival of the data across the plurality of processes running on the compute node, signaling completion of an operation performed by one or more of the plurality of processes, obtaining reservation slots by one or more of the plurality of processes, or combinations thereof.

  7. Cheaper Adjoints by Reversing Address Computations

    DOE PAGES

    Hascoët, L.; Utke, J.; Naumann, U.

    2008-01-01

    The reverse mode of automatic differentiation is widely used in science and engineering. A severe bottleneck for the performance of the reverse mode, however, is the necessity to recover certain intermediate values of the program in reverse order. Among these values are computed addresses, which traditionally are recovered through forward recomputation and storage in memory. We propose an alternative approach for recovery that uses inverse computation based on dependency information. Address storage constitutes a significant portion of the overall storage requirements. An example illustrates substantial gains that the proposed approach yields, and we show use cases in practical applications.

  8. Inherited Retinal Degenerative Disease Clinical Trials Network

    DTIC Science & Technology

    2014-12-01

    Network PRINCIPAL INVESTIGATOR: Patricia Zilliox., Ph.D. CONTRACTING ORGANIZATION: Foundation Fighting Blindness Clinical Research...fightblindness.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Foundation Fighting Blindness Clinical Research Institute

  9. Naming and Address in Afghan Society.

    ERIC Educational Resources Information Center

    Miran, M. Alam

    Forms of address in Afghan society reflect the relationships between the speakers as well as the society's structure. In Afghan Persian, or Dari, first, second, and last names have different semantic dimensions. Boys' first names usually consist of two parts or morphemes, of which one may be part of the father's name. Girls' names usually consist…

  10. Problem Solvers: Solutions--The Inaugural Address

    ERIC Educational Resources Information Center

    Dause, Emily

    2014-01-01

    Fourth graders in Miss Dause's and Mrs. Hicks's mathematics classes at South Mountain Elementary School in Dillsburg, Pennsylvania, worked with the data from the Inauagural Address problem that was previously published published in the February 2013 issue of "Teaching Children Mathematics". This activity allowed students to showcase…

  11. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Mailing addresses. 600.2 Section 600.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401...

  12. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Mailing addresses. 600.2 Section 600.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401...

  13. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Mailing addresses. 600.2 Section 600.2 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... (HFM-99), Center for Biologics Evaluation and Research, Food and Drug Administration, 1401...

  14. Transition through Teamwork: Professionals Address Student Access

    ERIC Educational Resources Information Center

    Bube, Sue Ann; Carrothers, Carol; Johnson, Cinda

    2016-01-01

    Prior to 2013, there was no collaboration around the transition services for deaf and hard of hearing students in Washington State. Washington had numerous agencies providing excellent support, but those agencies were not working together. It was not until January 29, 2013, when pepnet 2 hosted the Building State Capacity to Address Critical…

  15. Addressing Student Debt in the Classroom

    ERIC Educational Resources Information Center

    Perkins, David; Johnston, Tim; Lytle, Rick

    2016-01-01

    Student debt is a national concern. The authors address debt in the classroom to enhance students' understanding of the consequences of debt and the need for caution when financing their education. However, student feedback indicates this understanding has a delayed effect on borrowing behavior and underscores the importance of making difficult…

  16. Preservice Educators' Confidence in Addressing Sexuality Education

    ERIC Educational Resources Information Center

    Wyatt, Tammy Jordan

    2009-01-01

    This study examined 328 preservice educators' level of confidence in addressing four sexuality education domains and 21 sexuality education topics. Significant differences in confidence levels across the four domains were found for gender, academic major, sexuality education philosophy, and sexuality education knowledge. Preservice educators…

  17. 50 CFR 18.78 - Mailing address.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Mailing address. 18.78 Section 18.78 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED... PLANTS (CONTINUED) MARINE MAMMALS Notice and Hearing on Section 103 Regulations § 18.78 Mailing...

  18. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM Due Diligence § 674.44 Address searches. (a) If mail... litigation; (2) The account is assigned to the United States; or (3) The account is written off under §...

  19. Address Systems in "The Plum Plum Pickers"

    ERIC Educational Resources Information Center

    Geuder, Patricia A.

    1975-01-01

    The address systems in Raymond Barrio's "The Plum Plum Pickers" imply sociolinguistic differences between the Chicano and the Anglo characters. The kinds of sociolinguistic situations, the number of dyadic patterns, and the quantity of the dyadic patterns strongly suggest the differences. (Author)

  20. Registering Names and Addresses for Information Technology.

    ERIC Educational Resources Information Center

    Knapp, Arthur A.

    The identification of administrative authorities and the development of associated procedures for registering and accessing names and addresses of communications data systems are considered in this paper. It is noted that, for data communications systems using standards based on the Open Systems Interconnection (OSI) Reference Model specified by…