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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. 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.

  5. Addressing dual agency: getting specific about the expectations of professionalism.

    PubMed

    Tilburt, Jon C

    2014-01-01

    Professionalism requires that physicians uphold the best interests of patients while simultaneously insuring just use of health care resources. Current articulations of these obligations like the American Board of Internal Medicine (ABIM) Foundation's Physician Charter do not reconcile how these obligations fit together when they conflict. This is the problem of dual agency. The most common ways of dealing with dual agency: "bunkering"--physicians act as though societal cost issues are not their problem; "bailing"--physicians assume that they are merely agents of society and deliver care typically based on a strongly consequentialist public health ethic; or "balancing"--a vaguely specified attempt to uphold both patient welfare and societal need for judicious resource use simultaneously--all fail. Here I propose how the problem of dual agency might begin to be addressed with rigor and consistency. Without dealing with the dual agency problem and getting more specific about how to reconcile its norms when they conflict, the expectations of professionalism risk being written off as cute, nonbinding aphorisms from the medical profession. PMID:25127273

  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. PMID:25818714

  7. Software programs that address site-specific inventory characteristics issues.

    SciTech Connect

    Dare, J. H.; Cournoyer, M. E.

    2001-01-01

    The proper characterization of Hazardous, Mixed Low-Level, and Mixed Transuranic waste enhances productivity and safety. Hazardous material criteria that need to be considered include physical and health hazards inherent to the waste stream. Other factors that may influence characterization include: particulate diameter, complexing or chelating agent properties, lead, and mercury content, pressurized containers, and P-listed wastes. To meet these requirements are only a simple matter of generating a database with the proper fields. Manufactures and institutional databases bank huge sources of information, such as, work control documents, substance identification, container types, components of mixtures, physical property data, and regulatory data. In this report, utilization of commercially available software programs to take advantage of these resources in addressing waste characterization issues are presented. The application of user-friendly programs eliminates part of the tediousness associated with the complex requirements of certifying to general waste acceptance criteria with minimal impact on programmatic work. In other words, tapping into manufacturer and institutional database provides a way to take advantage of the combined expertise of these resources in managing a cost effective waste certification program as well as adding a quality assurance element to the program.

  8. 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

  9. 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 for submittal of plans, specifications,...

  10. 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

  11. Event-Specific Prevention: addressing college student drinking during known windows of risk.

    PubMed

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

    2007-11-01

    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 [DeJong, W. & Langford, L. M. (2002). A typology for campus-based alcohol prevention: Moving toward environmental management strategies. Journal of Studies on Alcohol, 140-147.] 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

  12. 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

  13. Clinical Behaviors for Addressing Religious/Spiritual Issues: Do We Practice What We Preach?

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Young, J. Scott; Fulton, Cheryl L.; Willis, Ben T.; Giordano, Amanda; Daniel, Laura Wyatt; Crockett, Jamie; Tate, B. Nicole; Welch, Metoka L.

    2013-01-01

    To determine if counselors integrate clinical behaviors for addressing religious/spiritual issues in counseling consistent with their ratings of the importance of such behaviors, the authors conducted a national survey of American Counseling Association (ACA) members. Seventy-eight ACA members rated the importance of and frequency with which they…

  14. Vocal Imitation in Parrots Allows Addressing of Specific Individuals in a Dynamic Communication Network

    PubMed Central

    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. PMID:23185424

  15. 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. PMID:23185424

  16. Education and Training to Address Specific Needs During the Career Progression of Surgeons.

    PubMed

    Sachdeva, Ajit K; Blair, Patrice Gabler; Lupi, Linda K

    2016-02-01

    Surgeons have specific education and training needs as they enter practice, progress through the core period of active practice, and then as they wind down their clinical work before retirement. These transitions and the career progression process, combined with the dynamic health care environment, present specific opportunities for innovative education and training based on practice-based learning and improvement, and continuous professional development methods. Cutting-edge technologies, blended models, simulation, mentoring, preceptoring, and integrated approaches can play critical roles in supporting surgeons as they provide the best surgical care throughout various phases of their careers. PMID:26612024

  17. SHAPING A NEW GENERATION OF HISPANIC CLINICAL AND TRANSLATIONAL RESEARCHERS ADDRESSING MINORITY HEALTH AND HEALTH DISPARITIES

    PubMed Central

    Estape, Estela S.; Segarra, Barbara; Baez, Adriana; Huertas, Aracelis; Diaz, Clemente; Frontera, Walter

    2012-01-01

    In 2011, research educators face significant challenges. Training programs in Clinical and Translational Research need to develop or enhance their curriculum to comply with new scientific trends and government policies. Curricula must impart the skills and competencies needed to help facilitate the dissemination and transfer of scientific advances at a faster pace than current health policy and practice. Clinical and translational researchers are facing also the need of new paradigms for effective collaboration, and resource sharing while using the best educational models. Both government and public policy makers emphasize addressing the goals of improving health quality and elimination of health disparities. To help achieve this goal, our academic institution is taking an active role and striving to develop an environment that fosters the career development of clinical and translational researchers. Consonant with this vision, in 2002 the University of Puerto Rico, Medical Sciences Campus School of Health Professions and School of Medicine initiated a multidisciplinary post-doctoral Master of Science in Clinical Research focused in training Hispanics who will address minority health and health disparities research. Recently, we proposed a curriculum revision to enhance this commitment in promoting competency-based curricula for clinician-scientists in clinical and translational sciences. The revised program will be a post-doctoral Master of Science in Clinical and Translational Research (MCTR), expanding its outreach by actively engaging in establishing new collaborations and partnerships that will increase our capability to diversify our educational efforts and make significant contributions to help reduce and eliminate the gap in health disparities. PMID:22263296

  18. [Clinical and biological specificities of female alcoholism].

    PubMed

    Limosin, F

    2002-01-01

    Even though the number of alcohol-dependent women is only about 1/3 of the number of alcoholic men, the alcoholism in women, by its clinical features and its course, is the source of therapeutic and economic stakes, particularly in young women among whom an increase of alcohol consumption related problems is reported. Another specificity of the female alcoholism is the lack of care seeking, whereas women have tendency globally to solicit more often care structures than men. Women represent only 1/4 of the overall treated alcoholic patients. The main explanation for this phenomenon is the pejorative social and moral connotation of the female alcoholism, with frequent feelings of shame and deep guilt, that also account for the frequency of hidden and lonely alcohol intakes. The female alcoholism is essentially characterized by an increased vulnerability to the toxic effects of the alcohol, whereas the pathological consumption starts later and with smaller daily amounts. Most studies have revealed a higher vulnerability in women to somatic complications directly attributable to the alcohol organs toxicity, such as hepatic cirrhosis and cardiovascular complications (high blood pressure, non obstructive cardiomyopathy). The reported brain morphological abnormalities could also occur more precociously in alcoholic women than in men. A decreased corpus callosum size among alcoholic women, but not in alcoholic men, was thus found in a recent study, compared with healthy controls. Among the different hypothesis proposed to explain this increased alcohol toxicity, the most incriminated is higher alcohol blood rates for the same ingested amount, mainly of the fact of a lower size with a weaker proportion of the bodily total water, but also of weaker concentrations of gastro-intestinal tract ADH, or of a longer metabolism during some menstrual phases. Indeed, some experimental studies on animal showed that the alcohol toxic effects may occur only from a threshold of alcohol

  19. Translating Life Course Theory to clinical practice to address health disparities.

    PubMed

    Cheng, Tina L; Solomon, Barry S

    2014-02-01

    Life Course Theory (LCT) is a framework that explains health and disease across populations and over time and in a powerful way, conceptualizes health and health disparities to guide improvements. It suggests a need to change priorities and paradigms in our healthcare delivery system. In "Rethinking Maternal and Child Health: The Life Course Model as an Organizing Framework," Fine and Kotelchuck identify three areas of rethinking that have relevance to clinical care: (1) recognition of context and the "whole-person, whole-family, whole-community systems approach;" (2) longitudinal approach with "greater emphasis on early ("upstream") determinants of health"; and (3) need for integration and "developing integrated, multi-sector service systems that become lifelong "pipelines" for healthy development". This paper discusses promising clinical practice innovations in these three areas: addressing social influences on health in clinical practice, longitudinal and vertical integration of clinical services and horizontal integration with community services and resources. In addition, barriers and facilitators to implementation are reviewed. PMID:23677685

  20. Translating Life Course Theory to Clinical Practice to Address Health Disparities

    PubMed Central

    Solomon, Barry S.

    2013-01-01

    Life Course Theory (LCT) is a framework that explains health and disease across populations and over time and in a powerful way, conceptualizes health and health disparities to guide improvements. It suggests a need to change priorities and paradigms in our healthcare delivery system. In “Rethinking Maternal and Child Health: The Life Course Model as an Organizing Framework,” Fine and Kotelchuck identify three areas of rethinking that have relevance to clinical care: (1) recognition of context and the “whole-person, whole-family, whole-community systems approach;” (2) longitudinal approach with “greater emphasis on early (“upstream”) determinants of health”; and (3) need for integration and “developing integrated, multi-sector service systems that become lifelong “pipelines” for healthy development”. This paper discusses promising clinical practice innovations in these three areas: addressing social influences on health in clinical practice, longitudinal and vertical integration of clinical services and horizontal integration with community services and resources. In addition, barriers and facilitators to implementation are reviewed. PMID:23677685

  1. 46 CFR 107.317 - Addresses for submittal of plans, specifications, and calculations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-MOBILE OFFSHORE DRILLING UNITS INSPECTION AND CERTIFICATION Plan Approval § 107.317 Addresses for...) The Officer in Charge, Marine Inspection, in the zone in which the unit is to be built or altered....

  2. 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%…

  3. Clinical Investigations in Mathematics Education. Thematic Addresses from the Fourth National Conference on Diagnostic and Prescriptive Mathematics.

    ERIC Educational Resources Information Center

    Speer, William R.

    Five invitational addresses presented at the Fourth National Conference of the Research Council for Diagnostic and Prescriptive Mathematics are included in this document. "The Nature of the Clinical Investigation" (Romberg and Uprichard) discusses the validity of clinical investigations and suggests guidelines for conducting such studies of…

  4. 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…

  5. Selective estrogen receptor modulators: tissue specificity and clinical utility

    PubMed Central

    Martinkovich, Stephen; Shah, Darshan; Planey, Sonia Lobo; Arnott, John A

    2014-01-01

    Selective estrogen receptor modulators (SERMs) are a diverse group of nonsteroidal compounds that function as agonists or antagonists for estrogen receptors (ERs) in a target gene-specific and tissue-specific fashion. SERM specificity involves tissue-specific expression of ER subtypes, differential expression of co-regulatory proteins in various tissues, and varying ER conformational changes induced by ligand binding. To date, the major clinical applications of SERMs are their use in the prevention and treatment of breast cancer, the prevention of osteoporosis, and the maintenance of beneficial serum lipid profiles in postmenopausal women. However, SERMs have also been found to promote adverse effects, including thromboembolic events and, in some cases, carcinogenesis, that have proven to be obstacles in their clinical utility. In this review, we discuss the mechanisms of SERM tissue specificity and highlight the therapeutic application of well-known and emergent SERMs. PMID:25210448

  6. 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

  7. 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…

  8. The ethical and clinical practice of disclosing raw test data: addressing the ongoing debate.

    PubMed

    Bush, Shane S; Martin, Thomas A

    2006-01-01

    Neuropsychologists are prone to having raw test data requested by colleagues, clients, and attorneys. Although questions of when and to whom neuropsychologists should release raw test data have been debated for years, uncertainty about how to address requests for raw test data persists. Although contradictions within and between ethical and legal guidelines exist, general bioethical principles, most ethical and professional guidelines, and federal copyright law support the responsibility of practitioners to maintain the security of neuropsychological tests, including raw test data. Neuropsychologists are best served by taking a proactive approach regarding the manner in which requests for raw test data are addressed. The purpose of this article is to provide the information necessary to make informed decisions regarding the release of raw test data; however, each neuropsychologist must ultimately choose to pursue a course of action that is simply ethically acceptable or one that is ethically preferable. PMID:17009884

  9. 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…

  10. Addressing ethical dilemmas in the clinical care of adolescents: an international view.

    PubMed

    Michaud, Pierre-André; Berg-Kelly, Kristina; Macfarlane, Aidan; Renteria, Saira-Christine; Wyss, Danielle; Benaroyo, Lazare

    2009-12-01

    This chapter reviews some basic concepts underlying ethical issues in adolescence and provides a step-by-step procedure to address ethical dilemmas involving minor adolescents, based on a deliberative approach. "Deliberation" with the patient, along with involving the opinion of relevant stakeholders if possible, allows for a careful, multidisciplinary examination of all options, the medical and psychosocial consequences, and the moral values stressed by each option. Although the final decision regarding which ethical option should be chosen usually belongs to the health care providers and his or her patient, the deliberative approach provides the ingredients for sound, unbiased decision-making. PMID:20653211

  11. 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…

  12. Some strategies to address the challenges of collecting observational data in a busy clinical environment.

    PubMed

    Jackson, Debra; McDonald, Glenda; Luck, Lauretta; Waine, Melissa; Wilkes, Lesley

    2016-01-01

    Studies drawing on observational methods can provide vital data to enhance healthcare. However, collecting observational data in clinical settings is replete with challenges, particularly where multiple data-collecting observers are used. Observers collecting data require shared understanding and training to ensure data quality, and particularly, to confirm accurate and consistent identification, discrimination and recording of data. The aim of this paper is to describe strategies for preparing and supporting multiple researchers tasked with collecting observational data in a busy, and often unpredictable, hospital environment. We hope our insights might assist future researchers undertaking research in similar settings. PMID:27188039

  13. 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

  14. Clinical challenges in addressing resistance to antimicrobial drugs in the twenty-first century.

    PubMed

    Septimus, E J; Kuper, K M

    2009-09-01

    It has been more than 60 years since Alexander Fleming discovered the drug that came to be known as penicillin. Antibiotics are now one of the most frequently used medications in the United States and are prescribed by medical professionals in almost every specialty. The past decade has seen an alarming increase in the number of pathogens that are resistant to antimicrobial drugs, in the hospital as well as in the community.(1) Among the gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus species are the biggest threats. The situation is even more alarming with respect to gram-negative pathogens, especially because there are currently no late clinical trials involving new anti-infective drugs that are active against these pathogens. PMID:19571803

  15. Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention in Clinical Practice.

    PubMed

    Battistoni, Allegra; Mastromarino, Vittoria; Volpe, Massimo

    2015-06-01

    Emerging evidence suggesting the possibility that interventions able to prevent cardiovascular disease (CVD) may also be effective in the prevention of cancer have recently stimulated great interest in the medical community. In particular, data from both experimental and observational studies have demonstrated that aspirin may play a role in preventing different types of cancer. Although the use of aspirin in the secondary prevention of CVD is well established, aspirin in primary prevention is not systematically recommended because the absolute cardiovascular event reduction is similar to the absolute excess in major bleedings. By adding to its cardiovascular prevention benefits, the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in primary prevention in favor of the latter and broaden the indication for treatment with aspirin in populations at average risk. Prospective and randomized studies are currently investigating the effect of aspirin in prevention of both cancer and CVD; however, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention already could be made on the basis of a balanced evaluation of the benefit/risk ratio. PMID:25873555

  16. Addressing Social Determinants of Health in a Clinic Setting: The WellRx Pilot in Albuquerque, New Mexico.

    PubMed

    Page-Reeves, Janet; Kaufman, Will; Bleecker, Molly; Norris, Jeffrey; McCalmont, Kate; Ianakieva, Veneta; Ianakieva, Dessislava; Kaufman, Arthur

    2016-01-01

    Although it is known that the social determinants of health have a larger influence on health outcomes than health care, there currently is no structured way for primary care providers to identify and address nonmedical social needs experienced by patients seen in a clinic setting. We developed and piloted WellRx, an 11-question instrument used to screen 3048 patients for social determinants in 3 family medicine clinics over a 90-day period. Results showed that 46% of patients screened positive for at least 1 area of social need, and 63% of those had multiple needs. Most of these needs were previously unknown to the clinicians. Medical assistants and community health workers then offered to connect patients with appropriate services and resources to address the identified needs. The WellRx pilot demonstrated that it is feasible for a clinic to implement such an assessment system, that the assessment can reveal important information, and that having information about patients' social needs improves provider ease of practice. Demonstrated feasibility and favorable outcomes led to institutionalization of the WellRx process at a university teaching hospital and influenced the state department of health to require managed care organizations to have community health workers available to care for Medicaid patients. PMID:27170801

  17. How to Use a Randomized Clinical Trial Addressing a Surgical Procedure: Users' Guide to the Medical Literature.

    PubMed

    Evaniew, Nathan; Carrasco-Labra, Alonso; Devereaux, P J; Tikkinen, Kari A O; Fei, Yutong; Bhandari, Mohit; Guyatt, Gordon

    2016-07-01

    Because surgical procedures require clinicians to develop and maintain procedural expertise and because blinding in randomized clinical trials of such therapies is often challenging, their critical appraisal raises unique issues. Risk of bias of trials of surgical procedures increases if investigators fail to rigorously conceal allocation and, where possible, to ensure blinding of those involved in the trial. Variability in surgeons' expertise can also increase bias and lead to important limitations in applicability. To address these issues, this Users' Guide to the Medical Literature reviews the use of remote randomization systems, blinding, sham-controlled trials, split-body trials, expertise-based trials, and mechanistic vs practical trials. Consideration of risk of bias and applicability issues will allow clinicians to make optimal use of trials addressing surgical procedures. PMID:27027568

  18. 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. PMID:23634479

  19. Stream specificity and asymmetries in feature binding and content-addressable access in visual encoding and memory.

    PubMed

    Huynh, Duong L; Tripathy, Srimant P; Bedell, Harold E; Ögmen, Haluk

    2015-01-01

    Human memory is content addressable-i.e., contents of the memory can be accessed using partial information about the bound features of a stored item. In this study, we used a cross-feature cuing technique to examine how the human visual system encodes, binds, and retains information about multiple stimulus features within a set of moving objects. We sought to characterize the roles of three different features (position, color, and direction of motion, the latter two of which are processed preferentially within the ventral and dorsal visual streams, respectively) in the construction and maintenance of object representations. We investigated the extent to which these features are bound together across the following processing stages: during stimulus encoding, sensory (iconic) memory, and visual short-term memory. Whereas all features examined here can serve as cues for addressing content, their effectiveness shows asymmetries and varies according to cue-report pairings and the stage of information processing and storage. Position-based indexing theories predict that position should be more effective as a cue compared to other features. While we found a privileged role for position as a cue at the stimulus-encoding stage, position was not the privileged cue at the sensory and visual short-term memory stages. Instead, the pattern that emerged from our findings is one that mirrors the parallel processing streams in the visual system. This stream-specific binding and cuing effectiveness manifests itself in all three stages of information processing examined here. Finally, we find that the Leaky Flask model proposed in our previous study is applicable to all three features. PMID:26382005

  20. Clinical improvement in psoriasis with specific targeting of interleukin-23.

    PubMed

    Kopp, Tamara; Riedl, Elisabeth; Bangert, Christine; Bowman, Edward P; Greisenegger, Elli; Horowitz, Ann; Kittler, Harald; Blumenschein, Wendy M; McClanahan, Terrill K; Marbury, Thomas; Zachariae, Claus; Xu, Danlin; Hou, Xiaoli Shirley; Mehta, Anish; Zandvliet, Anthe S; Montgomery, Diana; van Aarle, Frank; Khalilieh, Sauzanne

    2015-05-14

    Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1) groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and 13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples. PMID:25754330

  1. Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

    PubMed Central

    Morris, C D; Rose, A; Curwen, J; Hughes, A M; Wilson, D J; Webb, D J

    2005-01-01

    Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy. PMID:15956965

  2. 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

  3. 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

  4. 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

  5. The Buffalo Model: Shifting the Focus of Clinical Licensure Exams in Dentistry to Address Ethical Concerns Regarding Patient Care.

    PubMed

    Gambacorta, Joseph E; Glick, Michael; Anker, Ashley E; Shampaine, Guy S

    2016-06-01

    Most jurisdictions grant dental licensure to graduating students following successful completion of a clinical exam. Testing agencies, which are independent of dental schools, nevertheless conduct their exams at school facilities. Patient participation in these exams raises ethical concerns regarding such issues as unlicensed providers' performing irreversible procedures with minimal supervision and graduates' limited accessibility to provide follow-up treatment. To address these concerns, a collaborative effort between University at Buffalo School of Dental Medicine faculty and testing agency personnel was launched. The aims of this article are to describe the development and implementation of the resulting Buffalo Model, to highlight ethical advantages in its application, and to identify areas of improvement to be addressed in future iterations. With the Buffalo Model, modifications were made to the traditional exam format in order to integrate the exam into the school curriculum, enabling candidates to take it at various points during their fourth year. In addition, after calibration of school faculty members, 98.5% of cases verified by faculty were accepted by the Commission on Dental Competency Assessments for use in the exam. In two cases, restorative treatment completed during the exam did not meet the school's competency standard. This new approach ameliorates ethical concerns associated with clinical licensure exams because treatment is provided only to patients of record within a sequenced treatment plan and timely and appropriate treatment is provided to all patients. The results of this first year of implementation also suggest that calibrated faculty members will not show bias in the selection of lesions or competency evaluations of candidates. PMID:27251344

  6. 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

  7. User-specific interfaces for clinical data-management systems: an object-based approach.

    PubMed Central

    Wilton, R.

    1992-01-01

    Multiple user-specific visual interfaces are desirable in any computer-based clinical data-management system that is used by different people with different jobs to perform. The programming and maintenance problems of supporting multiple user interfaces to a single information system can be addressed by separating user-interface functionality from data-management subsystems, and by building user interfaces from object-based software components whose functionality is bound to an underlying server-client data-management architecture. Experience with this approach in a patient-tracking system suggests that this object-based approach is viable in the design of a user interface for a clinical information system. PMID:1482880

  8. 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

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

    PubMed

    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

  10. 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. PMID:21661367

  11. 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…

  12. 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…

  13. Locus-specific database domain and data content analysis: evolution and content maturation toward clinical use.

    PubMed

    Mitropoulou, Christina; Webb, Adam J; Mitropoulos, Konstantinos; Brookes, Anthony J; Patrinos, George P

    2010-10-01

    Genetic variation databases have become indispensable in many areas of health care. In addition, more and more experts are depositing published and unpublished disease-causing variants of particular genes into locus-specific databases (LSDBs). Some of these databases contain such extensive information that they have become known as knowledge bases. Here, we analyzed 1,188 LSDBs and their content for the presence or absence of 44 content criteria related to database features (general presentation, locus-specific information, database structure) and data content (data collection, summary table of variants, database querying). Our analyses revealed that several elements have helped to advance the field and reduce data heterogeneity, such as the development of specialized database management systems and the creation of data querying tools. We also identified a number of deficiencies, namely, the lack of detailed disease and phenotypic descriptions for each genetic variant and links to relevant patient organizations, which, if addressed, would allow LSDBs to better serve the clinical genetics community. We propose a structure, based on LSDBs and closely related repositories (namely, clinical genetics databases), which would contribute to a federated genetic variation browser and also allow the maintenance of variation data. PMID:20672379

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

    PubMed

    Cantalupo, Nancy Chi

    2014-03-12

    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. PMID:24626456

  15. [Posttraumatic stress disorder endophenotypes: several clinical dimensions for specific treatments].

    PubMed

    Auxéméry, Y

    2012-01-01

    Posttraumatic stress disorder is a syndrome with a very complex clinical that it is useful to describe according to a multidimensional approach. Following a critical review of the international literature, we have been able to highlight the genetic supports of posttraumatic stress disorder in the perspective of returning to the source of the clinical of this syndrome in order to steer its treatment better. We consider in succession the neuromodulation pathways involving dopamine, serotonine and noradrenaline to describe the hyperdomaminergic, hyposerotoninergic and hypernoradrenergic endophenotypes of posttraumatic stress disorder. Neurogenetic studies have affirmed two essential proposals. On the one hand, the pharmacological treatment of psychotraumatic disorders can be very closely adjusted to the different endophenotypes. On the other hand, the psychotherapeutic approach retains all its importance in the sense that it is the subjective implication that generated the trauma, subjectivity interacting with a genetic heritage and environmental factors integrating a social context. The changing definition of posttraumatic stress disorder over time comes from scientific exploration in part determined by a sociocultural context and, reciprocally, the psychic trauma is caused by the collapse of reassuring social values which were considered as immutable. The clinical is not developed according to fixed references: the evolution of neurogenetic techniques changes our perception of psychic traumas and the therapeutic possibilities. PMID:23167137

  16. Creating a lesson that addresses gender differences in physics testing a specific instructional technique in college level physics education

    NASA Astrophysics Data System (ADS)

    Lincoln, James J.

    Research-based instructional methods are applied in an effort to close the persistent gender gap in physics. Creating a short text on a limited topic using some of these methods could benefit female students specifically. A literature review showed research on the gender gap in physics and updated instructional methods for females. Two female physics students were interviewed and observations were conducted at a high performing all-girls school. A physics lab dialogue between two female physics students was recorded and analyzed, which informed the style and voice of the interactive dialogue lesson. An original written lesson intended to engage female physics students was created and tested on three classes of college-level physics students. The survey data, based on multiple choice and essay responses, measured the students' opinions of the lesson and their current textbook. Results showed the interactive lesson was preferred over the current text, and some students requested similar lessons.

  17. 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

  18. 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…

  19. 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.…

  20. 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. PMID:26963362

  1. 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…

  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. 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. PMID:22505906

  4. 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

  5. Evaluation of mtp40 genomic fragment amplification for specific detection of Mycobacterium tuberculosis in clinical specimens.

    PubMed Central

    Herrera, E A; Segovia, M

    1996-01-01

    A PCR assay based on the species-specific mtp40 genomic fragment was developed for the specific detection and identification of Mycobacterium tuberculosis in different uncultured clinical specimens. The aim of the study was to evaluate the clinical applicability of this target DNA in comparison with those of conventional microbiological methods and to compare the results obtained with those obtained after amplification with the IS6110 repetitive element. Discrepant results were interpreted in conjunction with the patients' clinical data, medical histories, and response to therapy. A total of 172 specimens from 162 patients with respiratory symptoms were tested, 101 specimens were obtained from 92 patients clinically suspected of having tuberculosis, and 71 specimens were obtained from 70 patients without known mycobacterial infection. The results of our study suggest that PCR amplification with the mtp40 genomic fragment provides a highly sensitive and specific technique for the detection of M. tuberculosis strains in clinical samples. It allows for the differentiation between M. tuberculosis and other related mycobacteria, including M. bovis, and is more specific than the IS6110 target. For these and other reasons, we propose that the mtp40 assay is a possible alternative for the specific direct detection of M. tuberculosis in clinical laboratories. PMID:8727885

  6. A Software System to Collect Expert Relevance Ratings of Medical Record Items for Specific Clinical Tasks

    PubMed Central

    Krishnaraj, Arun; Alkasab, Tarik K

    2014-01-01

    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. PMID:25600925

  7. 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. PMID:26385009

  8. Implementation of a Theory-based, Non-clinical Patient Navigator Program to Address Barriers in an Urban Cancer Center Setting.

    PubMed

    Fleisher, Linda; Miller, Suzanne M; Crookes, Danielle; Kandadai, Venk; Wen, Kuang Yi; Slamon, Rachel E; Chaivous, Jeanne

    2012-06-01

    Cancer patients face a myriad of psychosocial and practical issues. Especially challenging is the time from an initial diagnosis to the onset of treatment and patient navigation services are important to guide patients, especially underserved populations, through this maze of uncertainty. Here we report on the Pennsylvania Patient Navigator Demonstration Project (PaPND) designed to evaluate the acceptability, feasibility, and impact of a culturally and linguistically appropriate non-clinical navigator program. The development of the project, based on behavioral theory and community-based participatory research principles, is described. Forty-four cancer patients from diverse backgrounds participated, which included a baseline assessment, navigation services, and a four week and twelve week follow-up assessment. On average, participants experienced 1.8 barriers with transportation and insurance issues the most common barriers. The majority (56%) of the barriers required more than an hour of the navigator's time to address, with insurance, transportation and caregiver/support issues requiring the most time. Overall patients were fairly satisfied with the navigation services. The findings showed improvement patient's stress-related thoughts, cognition (understanding of their disease), expectancies and beliefs or values/goals, as well as self-efficacy of managing cancer related issues from the baseline to follow-up assessments. The evaluation results suggest that providing and connecting cancer patients to appropriate information to improve their understanding of their diagnosis and recommended treatments needs to be addressed, and where the integration of non-clinical and clinical navigation is essential. In addition, more attention to the assessment of psychosocial issues, such as the patients' emotional worries, and more comprehensive training in these areas would enhance navigation programs. PMID:25383260

  9. 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. PMID:23487896

  10. Evaluation of the first year of the Oxpal Medlink: A web-based partnership designed to address specific challenges facing medical education in the occupied Palestinian territories

    PubMed Central

    Ali, Mohammad A; Ali, Adam M; Patel, Ishita; MacGregor, Thomas; Shankar, Sushma; Cahill, Thomas J; Finlayson, Alexander ET; Mahmud, Imran

    2014-01-01

    Objectives To (1) evaluate educational needs of clinical students at Al-Quds University Medical School in the West Bank; (2) address these needs where possible using synchronous distance learning, with clinicians in Oxford providing case-based tutorials to undergraduates in the West Bank via an online platform (WizIQ) and (3) assess the impact of this education. Design Review of online OxPal Medlink database for tutorials held between March 2012 and April 2013. Needs assessment and evaluation of student and tutor experiences through online questionnaires, focus groups and semi-structured interviews. Setting Oxford University Hospitals, Oxford, UK, and Al-Quds University Medical School, Abu Dies, Palestine. Participants Doctors at Oxford University Hospitals and fourth-, fifth- and sixth-year medical students and faculty members at Al-Quds Medical School. Main outcome measures Number of tutorials, student participation, student-rated satisfaction and qualitative feedback from tutors and students. Results Students demonstrated strong theoretical knowledge but struggled to apply this in presentation-based scenarios. Between March 2012 and April 2013, 90 tutorials were delivered to 60 students. Feedback: >95% respondents rated tutorials as ‘Excellent’ or ‘Good’ and ‘Very’ or ‘Fairly’ relevant to their future practice in Palestine. Students reported the programme had modified their approach to patients but requested better synchronization with concurrent attachments and clarification of learning outcomes. Conclusions OxPal Medlink is a novel, web-based distance-learning partnership designed to overcome some of the challenges to local medical education in the occupied Palestinian territories. Evaluation of the first year indicates teaching is relevant to local practice and of high quality. This approach may have the potential to strengthen local capacity for medical education. PMID:25057373

  11. Analysis of antigen specific T cells in diabetes - Lessons from pre-clinical studies and early clinical trials.

    PubMed

    Krishnamurthy, Balasubramanian; Selck, Claudia; Chee, Jonathan; Jhala, Guarang; Kay, Thomas W H

    2016-07-01

    Antigen-specific immune tolerance promises to provide safe and effective therapies to prevent type 1 diabetes (T1D). Antigen-specific therapy requires two components: well-defined, clinically relevant autoantigens; and safe approaches to inducing tolerance in T cells specific for these antigens. Proinsulin is a critical autoantigen in both NOD mice, based on knockout mouse studies and induction of immune tolerance to proinsulin preventing disease whereas most antigens cannot, and also in human T1D based on proinsulin-specific T cells being found in the islets of affected individuals and the early appearance of insulin autoantibodies. Effective antigen-specific therapies that prevent T1D in humans have not yet been developed although doubt remains about the best molecular form of the antigen, the dose and the route of administration. Preclinical studies suggest that antigen specific therapy is most useful when administered before onset of autoimmunity but this time-window has not been tested in humans until the recent "pre-point" study. There may be a 'window of opportunity' during the neonatal period when 'vaccine' like administration of proinsulin for a short period may be sufficient to prevent diabetes. After the onset of autoimmunity, naive antigen-specific T cells have differentiated into antigen-experienced memory cells and the immune responses have spread to multiple antigens. Induction of tolerance at this stage becomes more difficult although recent studies have suggested generation of antigen-specific TR1 cells can inhibit memory T cells. Preclinical studies are required to identify additional 'help' that is required to induce tolerance to memory T cells and develop protocols for effective therapy in individuals with established autoimmunity. PMID:27083395

  12. HEPA and PARSE: Systematic discovery of clinically relevant tumor-specific antigens.

    PubMed

    Xu, Qing-Wen; Zhang, Yu; Wang, Xiao-Song

    2013-03-01

    The effective discovery of tumor-specific antigens (TSAs) holds the key for the development of new diagnostic assays and immunotherapeutic approaches against cancer. Here, we discuss our recently developed technologies, HEPA and PARSE, which allow for the systematic identification of TSAs, generating a reservoir of immunologically and clinically relevant targets. PMID:23802073

  13. 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,…

  14. Clinical Markers for Identification of Children with Specific Language Impairment (SLI)

    ERIC Educational Resources Information Center

    Rao, Prema K. S.; Prasitha, P.; Savitha, S.; Purushothaman, P.; Chitra, R.; Balaji, R.

    2010-01-01

    The condition of Specific Language Impairment (SLI) has aroused immense interest among researchers and practitioners owing to its unique characteristics and clinical manifestations. Children with SLI have offered rich data for understanding of language processing with reference to cognitive functions as well as structural aspects of a given…

  15. Age-Specificity of Clinical Dengue during Primary and Secondary Infections

    PubMed Central

    Thai, Khoa T. D.; Nishiura, Hiroshi; Hoang, Phuong Lan; Tran, Nga Thanh Thi; Phan, Giao Trong; Le, Hung Quoc; Tran, Binh Quang; Nguyen, Nam Van; de Vries, Peter J.

    2011-01-01

    Background This study aims to estimate the age-specific risks of clinical dengue attack (i.e., the risk of symptomatic dengue among the total number of dengue virus (DENV) infections) during primary and secondary infections. Methods We analyzed two pieces of epidemiological information in Binh Thuan province, southern Vietnam, i.e., age-specific seroprevalence and a community-wide longitudinal study of clinical dengue attack. The latter data set stratified febrile patients with DENV infection by age as well as infection parity. A simple modeling approach was employed to estimate the age-specific risks of clinical dengue attack during primary and secondary infections. Results Using the seroprevalence data, the force of infection was estimated to be 11.7% (95% confidence intervals (CI): 10.8–12.7) per year. Median age (and the 25–75 percentiles) of dengue fever patients during primary and secondary infections were 12 (9–20) and 20 (14–31) years, respectively. The estimated age-specific risk of clinical dengue increases as a function of age for both primary and secondary infections; the estimated proportion of symptomatic patients among the total number of infected individuals was estimated to be <7% for those aged <10 years for both primary and secondary infections, but increased as patients become older, reaching to 8–11% by the age of 20 years. Conclusions/Significance For both primary and secondary infections, higher age at DENV infection was shown to result in higher risk of clinical attack. Age as an important modulator of clinical dengue explains recent increase in dengue notifications in ageing countries in Southeast Asia, and moreover, poses a paradoxical problem of an increase in adult patients resulting from a decline in the force of infection, which may be caused by various factors including time-dependent variations in epidemiological, ecological and demographic dynamics. PMID:21713018

  16. Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper.

    PubMed

    Barosi, Giovanni; Vannucchi, Alessandro M; De Stefano, Valerio; Pane, Fabrizio; Passamonti, Francesco; Rambaldi, Alessandro; Saglio, Giuseppe; Barbui, Tiziano; Tura, Sante

    2014-02-01

    This article presents the results of group discussion among experts from SIE, SIES and GITMO societies aimed at highlighting unmet challenges in the management of Ph-neg myeloproliferative neoplasms (MPNs). The issues analyzed were: diagnosis of prefibrotic myelofibrosis; diagnosis of Ph-neg MPNs in the setting of splanchnic vein thrombosis (SVT); management of low-risk PV and low-risk ET patients with JAK2V617F mutation; molecular biomarkers in the prognostic evaluation of myelofibrosis (MF); ruxolitinib therapy in low-risk MF; therapy in patients with SVT-associated Ph-neg MPN; indications of splenectomy in MF. For each of these issues, proposals for advancement in clinical research were addressed. PMID:24378116

  17. 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

  18. 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.

  19. Automated Discovery of Patient-Specific Clinician Information Needs Using Clinical Information System Log Files

    PubMed Central

    Chen, Elizabeth S.; Cimino, James J.

    2003-01-01

    Knowledge about users and their information needs can contribute to better user interface design and organization of information in clinical information systems. This can lead to quicker access to desired information, which may facilitate the decision-making process. Qualitative methods such as interviews, observations and surveys have been commonly used to gain an understanding of clinician information needs. We introduce clinical information system (CIS) log analysis as a method for identifying patient-specific information needs and CIS log mining as an automated technique for discovering such needs in CIS log files. We have applied this method to WebCIS (Web-based Clinical Information System) log files to discover patterns of usage. The results can be used to guide design and development of relevant clinical information systems. This paper discusses the motivation behind the development of this method, describes CIS log analysis and mining, presents preliminary results and summarizes how the results can be applied. PMID:14728151

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

    PubMed Central

    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. PMID:26506897

  1. 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. PMID:19894486

  2. A Graphical Framework for Specification of Clinical Guidelines at Multiple Representation Levels

    PubMed Central

    Shalom, Erez; Shahar, Yuval

    2005-01-01

    Formalization of a clinical guideline for purposes of automated application and quality assessment mainly involves conversion of its free-text representation into a machine comprehensible representation, i.e., a formal language, thus enabling automated support. The main issues involved in this process are related to the collaboration between the expert physician and the knowledge engineer. We introduce GESHER - a graphical framework for specification of clinical guidelines at multiple representation levels. The GESHER architecture facilitates incremental specification through a set of views adapted to each representation level, enabling this process to proceed smoothly and in a transparent fashion, fostering extensive collaboration among the various types of users. The GESHER framework supports specification of guidelines at multiple representation levels, in more than one specification language, and uses the DeGeL digital guideline library architecture as its knowledge base. The GESHER architecture also uses a temporal abstraction knowledge base to store its declarative knowledge, and a standard medical-vocabularies server for generic specification of key terms, thus enabling reuse of the specification at multiple sites. PMID:16779126

  3. Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

    PubMed Central

    DiGiusto, DL; Cooper, LJN

    2007-01-01

    The production of clinical-grade T cells for adoptive immunotherapy has evolved from the ex vivo numerical expansion of tumor-infiltrating lymphocytes to sophisticated bioengineering processes often requiring cell selection, genetic modification and other extensive tissue culture manipulations, to produce desired cells with improved therapeutic potential. Advancements in understanding the biology of lymphocyte signaling, activation, homing and sustained in vivo proliferative potential have redefined the strategies used to produce T cells suitable for clinical investigation. When combined with new technical methods in cell processing and culturing, the therapeutic potential of T cells manufactured in academic centers has improved dramatically. Paralleling these technical achievements in cell manufacturing is the development of broadly applied regulatory standards that define the requirements for the clinical implementation of cell products with ever-increasing complexity. In concert with academic facilities operating in compliance with current good manufacturing practice, the prescribing physician can now infuse T cells with a highly selected or endowed phenotype that has been uniformly manufactured according to standard operating procedures and that meets federal guidelines for quality of investigational cell products. In this review we address salient issues related to the technical, immunologic, practical and regulatory aspects of manufacturing these advanced T-cell products for clinical use. PMID:17943498

  4. [Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].

    PubMed

    Akino, H; Suzuki, Y; Okada, K

    1998-08-01

    It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits. PMID:9750496

  5. 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

  6. Opening addresses.

    PubMed

    Chukudebelu, W O; Lucas, A O; Ransome-kuti, O; Akinla, O; Obayi, G U

    1988-01-01

    The theme of the 3rd International Conference of the Society of Gynecology and Obstetrics of Nigeria (SOGON) held October 26, 1986 in Enugu was maternal morbidity and mortality in Africa. The opening addresses emphasize the high maternal mortality rate in Africa and SOGON's dedication to promoting women's health and welfare. In order to reduce maternal mortality, the scope of this problem must be made evident by gathering accurate mortality rates through maternity care monitoring and auditing. Governments, health professionals, educators, behavioral scientists, and communication specialists have a responsibility to improve maternal health services in this country. By making the population aware of this problem through education, measures can be taken to reduce the presently high maternal mortality rates. Nigerian women are physically unprepared for childbirth; therefore, balanced diets and disease prevention should be promoted. Since about 40% of deliveries are unmanaged, training for traditional birth attendants should be provided. Furthermore, family planning programs should discourage teenage pregnancies, encourage birth spacing and small families, and promote the use of family planning techniques among men. The problem of child bearing and rearing accompanied by hard work should also be investigated. For practices to change so that maternal mortality rates can be reduced, attitudes must be changed such that the current rates are viewed as unacceptable. PMID:12179275

  7. 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

  8. 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

  9. Virulence Gene- and Pandemic Group-Specific Marker Profiling of Clinical Vibrio parahaemolyticus Isolates▿

    PubMed Central

    Meador, Carolyn E.; Parsons, Michele M.; Bopp, Cheryl A.; Gerner-Smidt, Peter; Painter, John A.; Vora, Gary J.

    2007-01-01

    Vibrio parahaemolyticus is a halophilic bacterium capable of causing food- and waterborne gastroenteritis, wound infections, and septicemia in humans. The organism has recently received increasing attention, as the emergence of a new clone, V. parahaemolyticus O3:K6, has resulted in the first documented pandemic spread of V. parahaemolyticus. We used microarray analyses to explore the presence of known virulence factors and genetic markers thought to be specific for V. parahaemolyticus O3:K6 and its clonal derivatives. Analyses of 48 human clinical isolates collected between 1997 and 2005 revealed that the V. parahaemolyticus chromosome 2 type III secretion system is not specifically associated with pandemic strains and can be found in tdh-negative (i.e., Kanagawa-negative) clinical isolates. These results highlight the genetic dynamism of V. parahaemolyticus and aid in refining the genetic definition of the pandemic group members. PMID:17301274

  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. 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

  12. 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

  13. Penile ulcer as a specific clinical manifestation of Waldenstrom’s macroglobulinemia*

    PubMed Central

    Oliveira, Cláudia Cardoso de Macedo; Bressa, José Antônio Nascimento; Mendes, Fernanda; Roncada, Eduardo Vinicius Mendes; Monteiro, Rodrigo; Abreu, Marilda Aparecida Milanez Morgado

    2016-01-01

    Waldenstrom’s macroglobulinemia is considered a lymphoma by the World Health Organization. Cutaneous lesions, particularly of a specific type, are rare occurring in 5% of patients. What draws attention in this case is the unusual cutaneous clinical manifestation and its location on the genitals, which has not been described in researched literature, therefore imposing differential diagnosis with other etiologies of genital ulcers. PMID:27192528

  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. 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. PMID:25895911

  16. Improving Treatment Trial Outcomes for Rett Syndrome: the development of Rett-specific anchors for the Clinical Global Impression Scale

    PubMed Central

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

    2015-01-01

    Rett syndrome is a genetically based neurodevelopmental disorder. While the clinical consequences of Rett syndrome are profound and life-long, 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 to 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. PMID:25895911

  17. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes

    PubMed Central

    Avsar, Timucin; Durası, İlknur Melis; Uygunoğlu, Uğur; Tütüncü, Melih; Demirci, Nuri Onat; Saip, Sabahattin; Sezerman, O. Uğur; Siva, Aksel; Tahir Turanlı, Eda

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications. PMID:25942430

  18. Pre-Clinical Assays Predict Pan-African Echis Viper Efficacy for a Species-Specific Antivenom

    PubMed Central

    Casewell, Nicholas R.; Cook, Darren A. N.; Wagstaff, Simon C.; Nasidi, Abdulsalami; Durfa, Nandul; Wüster, Wolfgang; Harrison, Robert A.

    2010-01-01

    Background Snakebite is a significant cause of death and disability in subsistent farming populations of sub-Saharan Africa. Antivenom is the most effective treatment of envenoming and is manufactured from IgG of venom-immunised horses/sheep but, because of complex fiscal reasons, there is a paucity of antivenom in sub-Saharan Africa. To address the plight of thousands of snakebite victims in savannah Nigeria, the EchiTAb Study Group organised the production, testing and delivery of antivenoms designed to treat envenoming by the most medically-important snakes in the region. The Echis saw-scaled vipers have a wide African distribution and medical importance. In an effort to maximise the clinical utility of scarce antivenom resources in Africa, we aimed to ascertain, at the pre-clinical level, to what extent the E. ocellatus-specific EchiTAbG antivenom, which was designed specifically for Nigeria, neutralised the lethal activity of venom from two other African species, E. pyramidum leakeyi and E. coloratus. Methodology/Principal Findings Despite apparently quite distinctive venom protein profiles, we observed extensive cross-species similarity in the immuno-reactivity profiles of Echis species-specific antisera. Using WHO standard pre-clinical in vivo tests, we determined that the monospecific EchiTAbG antivenom was as effective at neutralising the venom-induced lethal effects of E. pyramidum leakeyi and E. coloratus as it was against E. ocellatus venom. Under the restricted conditions of this assay, the antivenom was ineffective against the lethal effects of venom from the non-African Echis species, E. carinatus sochureki. Conclusions/Significance Using WHO-recommended pre-clinical tests we have demonstrated that the new anti-E. ocellatus monospecific antivenom EchiTAbG, developed in response to the considerable snakebite-induced mortality and morbidity in Nigeria, neutralised the lethal effects of venoms from Echis species representing each taxonomic group of this

  19. 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

    2016-07-01

    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. PMID:26098130

  20. 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. PMID:27110562

  1. 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

  2. President's Address

    PubMed Central

    Moore, John

    1928-01-01

    The paper recalls how matters veterinary were regarded forty-six years ago, what has been achieved since, and future progress is reflected. The paper is divided into parts relating respectively to: (a) medicine; (b) surgery (c) teaching and research; (d) administration. Formerly, glanders and farcy, and rabies, though acknowledged as contagious and specific, were also believed to be of spontaneous origin. Experiences with regard to these two diseases, and the mallein test for glanders, are related. The discovery of the Bacillus anthracis led to the development of veterinary research, but for some time confusion existed. Tuberculosis was believed to be endogenous and the result of the absorption of caseous products of a previous inflammation. Treatment of “milk fever” in cows by udder inflation and biochemistry in relation to that disease are considered. The advance in veterinary surgery stands out most prominently; in canine practice, operations are now attempted which were never thought possible in the early days. Allusion is made to the recent formidable operations for the cure of “windsucking” in horses, and for traumatic pericarditis in bovines. The powers of observance of the old practitioners in diagnosing lameness, and some of the old methods of treatment for lameness, are supported. The great progress in veterinary research is referred to, also its advantages from an imperial point of view. The causative agents of those diseases which are at present ultravisible, particularly foot-and-mouth disease, will probably be found, and better methods of prevention result. In training, thorough instruction in animal physiology, animal nutrition and biochemistry is advocated, also affiliation of veterinary colleges to universities, the individuality of such colleges, and the one-portal system of qualification being maintained. PMID:19986709

  3. Clinical Correlates of Awareness for Balance, Function, and Memory: Evidence for the Modality Specificity of Awareness

    PubMed Central

    O'Connell, Megan E.; Crossley, Margaret; Morgan, Debra

    2014-01-01

    Awareness in dementia is increasingly recognized not only as multifactorial, but also as domain specific. We demonstrate differential clinical correlates for awareness of daily function, awareness of memory, and the novel exploration of awareness of balance. Awareness of function was higher for participants with mild cognitive impairment (aMCI and non-aMCI) than for those with dementia (due to Alzheimer disease; AD and non-AD), whereas awareness of memory was higher for both non-aMCI and non-AD dementia patients than for those with aMCI or AD. Balance awareness did not differ based on diagnostic subgroup. Awareness of function was associated with instrumental activities of daily living and caregiver burden. In contrast, awareness of balance was associated with fall history, balance confidence, and instrumental activities of daily living. Clinical correlates of awareness of memory depended on diagnostic group: associations held with neuropsychological variables for non-AD dementia, but for patients with AD dementia, depression and instrumental activities of daily living were clinical correlates of memory awareness. Together, these data provide support for the hypothesis that awareness and dementia are not unitary and are, instead, modality specific. PMID:24551452

  4. Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

    PubMed

    Scahill, Rachael I; Hobbs, Nicola Z; Say, Miranda J; Bechtel, Natalie; Henley, Susie M D; Hyare, Harpreet; Langbehn, Douglas R; Jones, Rebecca; Leavitt, Blair R; Roos, Raymund A C; Durr, Alexandra; Johnson, Hans; Lehéricy, Stéphane; Craufurd, David; Kennard, Christopher; Hicks, Stephen L; Stout, Julie C; Reilmann, Ralf; Tabrizi, Sarah J

    2013-03-01

    TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD. PMID:22102212

  5. 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

  6. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data.

    PubMed

    Ferré, Marc; Caignard, Angélique; Milea, Dan; Leruez, Stéphanie; Cassereau, Julien; Chevrollier, Arnaud; Amati-Bonneau, Patrizia; Verny, Christophe; Bonneau, Dominique; Procaccio, Vincent; Reynier, Pascal

    2015-01-01

    Autosomal-dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, due to mutations in the optic atrophy 1 gene (OPA1) in about 60%-80% of cases. At present, the clinical heterogeneity of patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published the first locus-specific database (LSDB) dedicated to OPA1, a large amount of new clinical and genetic knowledge has emerged, prompting us to update this database. We have used the Leiden Open-Source Variation Database to develop a clinico-biological database, aiming to add clinical phenotypes related to OPA1 variants. As a first step, we validated this new database by registering several patients previously reported in the literature, as well as new patients from our own institution. Contributors may now make online submissions of clinical and molecular descriptions of phenotypes due to OPA1 variants, including detailed ophthalmological and neurological data, with due respect to patient anonymity. The updated OPA1 LSDB (http://opa1.mitodyn.org/) should prove useful for molecular diagnoses, large-scale variant statistics, and genotype-phenotype correlations in ADOA studies. PMID:25243597

  7. [Herd-specific estimation of milk yield reduction due to recurrent clinical mastitis].

    PubMed

    Zoche-Golob, Veit; Spilke, Joachim

    2013-01-01

    To decide about investments in preventive measures improving udder health it is important that the farmer knows the monetary loss due to mastitis on his specific farm. The Saxon dairy herd improvement association (Sächsischer LandeskontrolIverband e.V., LKV) is developing a computer program called "Daten- und Informationsplattform Tier (DIT)"which determines - among other analyses - the milk loss caused by mastitis for a specific herd based on individual cow's mastitis and daily milk yield data. The present article introduces the linear mixed model which is taken as a basis for calculating the reduction in performance through clinical mastitis. The short and long term decrease in daily milk yield is described by expanding the lactation curve model of Ali and Schaeffer (1987). For falculating the short term drop, the model includes the laps of time in days since the mastitis incident as secon-ddegree polynomial. The coefficients are estimaged specifically for the first respectively every following case of mastitis (class of episode). Classes of episode are also considered calculating the long term decrease by estimating lactation curves without mastitis as well as corresponding to the classes of episode. By integrating the statistic software R (R Development Core Team, 2012) into the processes of the DIT the estimation of the farm specific model parameters is largely automated on the servers of the LKV.Thereby, milk yield can be estimated for every day in milk according to episode number and laps of time since the incident or with no mastitis incident respectively for a particular period of time in a specific dairy herd. The loss resulting from reduced performance due to clinical mastitis is specified by adding up the differences and can serve as a valuable basis for management decisions. PMID:23901581

  8. [Technical specifications for rational clinical use of parenterally administered Chinese medicine (draft version for comments)].

    PubMed

    Xie, Yan-Ming; Li, Ming-Quan; Zhang, Yun-Ling; Ma, Rong; Xian, Shao-Xiang; Liu, Jian; Li, Su-Yun; Zhao, Yu-Bin

    2013-09-01

    The regulations on basic clinical use of parenterally administered Chinese medicine, issued jointly in 2008, by the ministry of health (MOH), China food and drug administration (SFDA) and the state administration of traditional Chinese medicine (SATCM). Integrating actual clinical practice, these presented doctors and nurses with detailed specifications for the safe use of parenterally administered Chinese medicine. The regulations emphasize the use of Chinese medicine pattern differentiation, use in strict accordance with instructions, and they prohibit use combined with other medicines. The emphasis of the regulations are practicality and operability, and provide meaningful guidance to doctors and nurses for the rational and safe use of parenterally administered Chinese medicine, to reduce adverse reactions/adverse events caused by improper use. PMID:24471306

  9. Clinical survey of hantavirus in southern Brazil and the development of specific molecular diagnosis tools.

    PubMed

    Raboni, Sonia M; Rubio, Gisélia; DE Borba, Luana; Zeferino, Aurélio; Skraba, Irene; Goldenberg, Samuel; Dos Santos, Claudia N Duarte

    2005-06-01

    Hantavirus pulmonary syndrome (HPS) is an emerging disease caused by an increasing number of distinct hantavirus serotypes found worldwide. It is also a very severe immune disease. It progresses quickly and is associated with a high mortality rate. At the prodrome phase, hantavirosis symptoms can resemble those of other infectious diseases such as leptospirosis and influenza. Thus, prognosis could be improved by developing a rapid and sensitive diagnostic test for hantavirus infection, and by improving knowledge about clinical aspects of this disease. This study describes clinical features and laboratory parameters throughout the course of HPS in 98 patients. We report the seasonality and regional distribution of this disease in Paraná State, Brazil during the last seven years. In addition, we evaluated a specific molecular diagnostic test based on a nested reverse transcriptase-polymerase chain reaction for the detection of hantaviruses circulating in Brazil. PMID:15964966

  10. 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

  11. Addressing Loss of Efficiency Due to Misclassification Error in Enriched Clinical Trials for the Evaluation of Targeted Therapies Based on the Cox Proportional Hazards Model

    PubMed Central

    Tsai, Chen-An; Lee, Kuan-Ting; Liu, Jen-pei

    2016-01-01

    A key feature of precision medicine is that it takes individual variability at the genetic or molecular level into account in determining the best treatment for patients diagnosed with diseases detected by recently developed novel biotechnologies. The enrichment design is an efficient design that enrolls only the patients testing positive for specific molecular targets and randomly assigns them for the targeted treatment or the concurrent control. However there is no diagnostic device with perfect accuracy and precision for detecting molecular targets. In particular, the positive predictive value (PPV) can be quite low for rare diseases with low prevalence. Under the enrichment design, some patients testing positive for specific molecular targets may not have the molecular targets. The efficacy of the targeted therapy may be underestimated in the patients that actually do have the molecular targets. To address the loss of efficiency due to misclassification error, we apply the discrete mixture modeling for time-to-event data proposed by Eng and Hanlon [8] to develop an inferential procedure, based on the Cox proportional hazard model, for treatment effects of the targeted treatment effect for the true-positive patients with the molecular targets. Our proposed procedure incorporates both inaccuracy of diagnostic devices and uncertainty of estimated accuracy measures. We employed the expectation-maximization algorithm in conjunction with the bootstrap technique for estimation of the hazard ratio and its estimated variance. We report the results of simulation studies which empirically investigated the performance of the proposed method. Our proposed method is illustrated by a numerical example. PMID:27120450

  12. 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. PMID:26302854

  13. Prevalence of Chlamydia pneumoniae specific antibodies in different clinical situations and healthy subjects in Izmir, Turkey.

    PubMed

    Gencay, M; Dereli, D; Ertem, E; Serter, D; Puolakkainen, M; Saikku, P; Boydak, B; Dereli, S; Ozbakkaloglu, B; Yorgancioglu, A; Tez, E

    1998-07-01

    Serological markers for Chlamydia pneumoniae were investigated by using the microimmunofluorescence (MIF) test in various age and patient groups in a specific area in Turkey. IgG seropositivity to C. pneumoniae was 64.3% and 18.7% in healthy adults and children, respectively. The highest positivity rate (77%) was in the 15-19 age group. Among the groups investigated, serological findings revealed a possible etiological association between C. pneumoniae and the clinical condition in the groups with acute myocardial infarction, atypical pneumoniae and chronic obstructive pulmonary disease. PMID:9744685

  14. Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity.

    PubMed

    Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

    2011-01-01

    AIMS: To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. STUDY DESIGN: Prospective study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. METHODOLOGY: We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock's criteria. RESULTS: Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. CONCLUSION: These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2). PMID:22993721

  15. 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…

  16. 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. PMID:21985650

  17. Generalized and Specific Cognitive Performance in Clinical High-Risk Cohorts: A Review Highlighting Potential Vulnerability Markers for Psychosis

    PubMed Central

    Brewer, Warrick J.; Wood, Stephen J.; Phillips, Lisa J.; Francey, Shona M.; Pantelis, Christos; Yung, Alison R.; Cornblatt, Barbara; McGorry, Patrick D.

    2006-01-01

    Cognitive deficits are a core feature of established psychotic illnesses. However, the association between cognition and emerging psychosis is less understood. While there is some evidence that cognitive deficits are present prior to the onset of psychosis, findings are not consistent. In this article we provide an overview of the more general cognitive findings available from genetic high-risk studies, retrospective studies, and birth cohort studies. We then focus the review on neuropsychological performance in clinically “at-risk” groups. Overall, general cognitive ability as assessed by established batteries appears to remain relatively intact in these ultra-high risk cohorts and is a poor predictor close to illness onset relative to other vulnerability factors. Further decline may occur with illness progression, more consistent with state relative to trait factors. In addition, most established cognitive tasks involve several relatively discrete cognitive subprocesses, where findings from general batteries of subtests may mask specific deficits. In this context, our review suggests that relatively specific olfactory identification and spatial working memory deficits exist prior to illness onset and may be more potent trait markers for psychosis than cognitively dense tasks such as verbal memory. Suggestions for further research address the importance of standardization of inclusion criteria and the maintenance of basic neuropsychological assessment to allow better comparison of findings across centers. Further, in order to better understand the aetiopathology of cognitive dysfunction in psychosis, more experimental, hypothesis-driven measures of discrete cognitive processes are required. Delineation of the relationship between specific cognitive ability and symptoms from data-driven approaches may improve our understanding of the role of cognition during psychosis onset. PMID:16782759

  18. Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.

    PubMed

    Cejas, Paloma; Li, Lewyn; O'Neill, Nicholas K; Duarte, Melissa; Rao, Prakash; Bowden, Michaela; Zhou, Chensheng W; Mendiola, Marta; Burgos, Emilio; Feliu, Jaime; Moreno-Rubio, Juan; Guadalajara, Héctor; Moreno, Víctor; García-Olmo, Damián; Bellmunt, Joaquim; Mullane, Stephanie; Hirsch, Michelle; Sweeney, Christopher J; Richardson, Andrea; Liu, X Shirley; Brown, Myles; Shivdasani, Ramesh A; Long, Henry W

    2016-06-01

    Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation. PMID:27111282

  19. The Impact of Specific Viruses on Clinical Outcome in Children Presenting with Acute Heart Failure

    PubMed Central

    Gagliardi, Maria Giulia; Fierabracci, Alessandra; Pilati, Mara; Chinali, Marcello; Bassano, Carlo; Saura, Francesca; Giovannoni, Isabella; Francalanci, Paola

    2016-01-01

    The presence and type of viral genomes have been suggested as the main etiology for inflammatory dilated cardiomyopathy. Information on the clinical implication of this finding in a large population of children is lacking. We evaluated the prevalence, type, and clinical impact of specific viral genomes in endomyocardial biopsies (EMB) collected between 2001 and 2013 among 63 children admitted to our hospital for acute heart failure (median age 2.8 years). Viral genome was searched by polymerase chain reaction (PCR). Patients underwent a complete two-dimensional echocardiographic examination at hospital admission and at discharge and were followed-up for 10 years. Twenty-seven adverse events (7 deaths and 20 cardiac transplantations) occurred during the follow-up. Viral genome was amplified in 19/63 biopsies (35%); PVB19 was the most commonly isolated virus. Presence of specific viral genome was associated with a significant recovery in ejection fraction, compared to patients without viral evidence (p < 0.05). In Cox-regression analysis, higher survival rate was related to virus-positive biopsies (p < 0.05). When comparing long-term prognosis among different viral groups, a trend towards better prognosis was observed in the presence of isolated Parvovirus B19 (PVB19) (p = 0.07). In our series, presence of a virus-positive EMB (mainly PVB19) was associated with improvement over time in cardiac function and better long-term prognosis. PMID:27043551

  20. The Impact of Specific Viruses on Clinical Outcome in Children Presenting with Acute Heart Failure.

    PubMed

    Gagliardi, Maria Giulia; Fierabracci, Alessandra; Pilati, Mara; Chinali, Marcello; Bassano, Carlo; Saura, Francesca; Giovannoni, Isabella; Francalanci, Paola

    2016-01-01

    The presence and type of viral genomes have been suggested as the main etiology for inflammatory dilated cardiomyopathy. Information on the clinical implication of this finding in a large population of children is lacking. We evaluated the prevalence, type, and clinical impact of specific viral genomes in endomyocardial biopsies (EMB) collected between 2001 and 2013 among 63 children admitted to our hospital for acute heart failure (median age 2.8 years). Viral genome was searched by polymerase chain reaction (PCR). Patients underwent a complete two-dimensional echocardiographic examination at hospital admission and at discharge and were followed-up for 10 years. Twenty-seven adverse events (7 deaths and 20 cardiac transplantations) occurred during the follow-up. Viral genome was amplified in 19/63 biopsies (35%); PVB19 was the most commonly isolated virus. Presence of specific viral genome was associated with a significant recovery in ejection fraction, compared to patients without viral evidence (p < 0.05). In Cox-regression analysis, higher survival rate was related to virus-positive biopsies (p < 0.05). When comparing long-term prognosis among different viral groups, a trend towards better prognosis was observed in the presence of isolated Parvovirus B19 (PVB19) (p = 0.07). In our series, presence of a virus-positive EMB (mainly PVB19) was associated with improvement over time in cardiac function and better long-term prognosis. PMID:27043551

  1. Deep transcriptome profiling of clinical Klebsiella pneumoniae isolates reveals strain and sequence type-specific adaptation.

    PubMed

    Bruchmann, Sebastian; Muthukumarasamy, Uthayakumar; Pohl, Sarah; Preusse, Matthias; Bielecka, Agata; Nicolai, Tanja; Hamann, Isabell; Hillert, Roger; Kola, Axel; Gastmeier, Petra; Eckweiler, Denitsa; Häussler, Susanne

    2015-11-01

    Health-care-associated infections by multi-drug-resistant bacteria constitute one of the greatest challenges to modern medicine. Bacterial pathogens devise various mechanisms to withstand the activity of a wide range of antimicrobial compounds, among which the acquisition of carbapenemases is one of the most concerning. In Klebsiella pneumoniae, the dissemination of the K. pneumoniae carbapenemase is tightly connected to the global spread of certain clonal lineages. Although antibiotic resistance is a key driver for the global distribution of epidemic high-risk clones, there seem to be other adaptive traits that may explain their success. Here, we exploited the power of deep transcriptome profiling (RNA-seq) to shed light on the transcriptomic landscape of 37 clinical K. pneumoniae isolates of diverse phylogenetic origins. We identified a large set of 3346 genes which was expressed in all isolates. While the core-transcriptome profiles varied substantially between groups of different sequence types, they were more homogenous among isolates of the same sequence type. We furthermore linked the detailed information on differentially expressed genes with the clinically relevant phenotypes of biofilm formation and bacterial virulence. This allowed for the identification of a diminished expression of biofilm-specific genes within the low biofilm producing ST258 isolates as a sequence type-specific trait. PMID:26261087

  2. Clinical Potential of Antigen-Specific Therapies in Type 1 Diabetes

    PubMed Central

    Coppieters, Ken T.; Sehested Hansen, Birgit; von Herrath, Matthias G.

    2012-01-01

    In type 1 diabetes (T1D), pancreatic beta-cells are attacked and destroyed by the immune system, which leads to a loss of endogenous insulin secretion. The desirable outcome of therapeutic intervention in autoimmune diseases is the restoration of immune tolerance to prevent organ damage. Past trials with immune suppressive drugs highlight the fact that T1D is in principle a curable condition. However, the barrier in T1D therapy in terms of drug safety is set particularly high because of the predominantly young population and the good prognosis associated with modern exogenous insulin therapy. Thus, there is a general consensus that chronic immune suppression is associated with unacceptable long-term safety risks. On the other hand, immune-modulatory biologicals have recently failed to confer significant protection in phase 3 clinical trials. However, the concept of antigen-specific tolerization may offer a unique strategy to safely induce long-term protection against T1D. In this review, we analyze the potential reasons for the failure of the different tolerization therapies, and describe how the concept of antigen-specific toleraization may overcome the obstacles associated with clinical therapy in T1D. PMID:23804270

  3. Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.

    PubMed Central

    Cohen, M G; Pollard, K M; Webb, J

    1992-01-01

    Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited. PMID:1540040

  4. The prostate-specific membrane antigen: Lessons and current clinical implications from 20 years of research

    PubMed Central

    Ristau, Benjamin T.; O’Keefe, Denise S.; Bacich, Dean J.

    2014-01-01

    Objective Despite a multitude of detection and treatment advances in the past two decades, prostate cancer remains the second leading cause of cancer death among men in the United States. Technological evolution and expanding knowledge of tumor biomarkers have invigorated exploration in prostate cancer therapeutics. Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer biomarkers successfully cloned. Since that time, it has been characterized as the prototypical cell-surface marker for prostate cancer and has been the subject of intense clinical inquiry. We review the relevant research in PSMA on the 20th anniversary of its cloning. Methods and materials A PubMed® search using the keywords “prostate-specific membrane antigen” or “glutamate carboxypeptidase II” provided 1019 results. An additional 3 abstracts were included from scientific meetings. Articles were vetted by title and abstract with emphasis placed on those with clinically relevant findings. Results Sixty articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its structure and function were further delineated in the ensuing decade. Consensus sites of expression in normal physiology are prostate, kidney, nervous system, and small intestine. PSMA has been implicated in the neovasculature of several tumors including urothelial and renal cell carcinomas. In prostate cancer, expression of PSMA is directly related to Gleason grade. PSMA has been tested both in imaging and therapeutics in a number of prostate cancer clinical trials. Several recent approaches to target PSMA include use of small molecule inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted prodrug therapy. Future study of PSMA in prostate cancer might focus on its intracellular functions and possible role in tumor neurogenesis. Conclusions Twenty years from its discovery, PSMA represents a viable biomarker and treatment target in prostate cancer. Research to

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

    PubMed

    Salvadori, Maurizio; Bertoni, Elisabetta

    2014-03-24

    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. Patient-specific instrumentation does not improve radiographic alignment or clinical outcomes after total knee arthroplasty.

    PubMed

    Huijbregts, Henricus J T A M; Khan, Riaz J K; Sorensen, Emma; Fick, Daniel P; Haebich, Samantha

    2016-08-01

    Background and purpose - Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA) has been introduced to improve alignment and reduce outliers, increase efficiency, and reduce operation time. In order to improve our understanding of the outcomes of patient-specific instrumentation, we conducted a meta-analysis. Patients and methods - We identified randomized and quasi-randomized controlled trials (RCTs) comparing patient-specific and conventional instrumentation in TKA. Weighted mean differences and risk ratios were determined for radiographic accuracy, operation time, hospital stay, blood loss, number of surgical trays required, and patient-reported outcome measures. Results - 21 RCTs involving 1,587 TKAs were included. Patient-specific instrumentation resulted in slightly more accurate hip-knee-ankle axis (0.3°), coronal femoral alignment (0.3°, femoral flexion (0.9°), tibial slope (0.7°), and femoral component rotation (0.5°). The risk ratio of a coronal plane outlier (> 3° deviation of chosen target) for the tibial component was statistically significantly increased in the PSI group (RR =1.64). No significance was found for other radiographic measures. Operation time, blood loss, and transfusion rate were similar. Hospital stay was significantly shortened, by approximately 8 h, and the number of surgical trays used decreased by 4 in the PSI group. Knee Society scores and Oxford knee scores were similar. Interpretation - Patient-specific instrumentation does not result in clinically meaningful improvement in alignment, fewer outliers, or better early patient-reported outcome measures. Efficiency is improved by reducing the number of trays used, but PSI does not reduce operation time. PMID:27249110

  7. Clinical relevance of multiple antibody specificity testing in anti-phospholipid syndrome and recurrent pregnancy loss

    PubMed Central

    Tebo, A E; Jaskowski, T D; Hill, H R; Branch, D W

    2008-01-01

    We wanted to evaluate whether testing for anti-phosholipid antibodies other than anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) immunoglobulin (Ig)G and IgM identifies patients with recurrent pregnancy loss (RPL) who may be positive for anti-phospholipid syndrome (APS). In a cross-sectional study comprising 62 patients with APS, 66 women with RPL, 50 healthy blood donors and 24 women with a history of successful pregnancies, we tested IgM and IgG antibodies to phosphatidic acid, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl inositol and phosphatidyl serine with and without beta-2 glycoprotein I (β2GPI) from a single manufacturer as well as aCL and aβ2GPI antibodies. Diagnostic accuracies of individual and combined anti-phospholipid (aPL) assays were assessed by computing sensitivities, specificities, positive predictive values and negative predictive values together with their 95% confidence intervals. There was a general trend for increased sensitivities in the presence of β2GPI co-factor with significant effect for certain specificities. The overall combined sensitivity of the non-recommended aPL assays was not significantly higher than that of the aCL and aB2GPI tests. Multiple aPL specificities in RPL group is not significantly different from controls and therefore of no clinical significance. PMID:18826497

  8. Clinical relevance of multiple antibody specificity testing in anti-phospholipid syndrome and recurrent pregnancy loss.

    PubMed

    Tebo, A E; Jaskowski, T D; Hill, H R; Branch, D W

    2008-12-01

    We wanted to evaluate whether testing for anti-phosholipid antibodies other than anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (abeta2GPI) immunoglobulin (Ig)G and IgM identifies patients with recurrent pregnancy loss (RPL) who may be positive for anti-phospholipid syndrome (APS). In a cross-sectional study comprising 62 patients with APS, 66 women with RPL, 50 healthy blood donors and 24 women with a history of successful pregnancies, we tested IgM and IgG antibodies to phosphatidic acid, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl glycerol, phosphatidyl inositol and phosphatidyl serine with and without beta-2 glycoprotein I (beta2GPI) from a single manufacturer as well as aCL and abeta2GPI antibodies. Diagnostic accuracies of individual and combined anti-phospholipid (aPL) assays were assessed by computing sensitivities, specificities, positive predictive values and negative predictive values together with their 95% confidence intervals. There was a general trend for increased sensitivities in the presence of beta2GPI co-factor with significant effect for certain specificities. The overall combined sensitivity of the non-recommended aPL assays was not significantly higher than that of the aCL and aB2GPI tests. Multiple aPL specificities in RPL group is not significantly different from controls and therefore of no clinical significance. PMID:18826497

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

    PubMed

    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

  11. Probiotics: a practical review of their role in specific clinical scenarios.

    PubMed

    Jenkins, Barry; Holsten, Steven; Bengmark, Stig; Martindale, Robert

    2005-04-01

    The use of probiotics (live viable microbial organisms) in the treatment of specific diseases has evolved into an extremely valuable option yet to be optimally used in clinical medicine. Probiotics have been shown to have immunomodulating properties and enhance the mucosal barrier. This review will briefly discuss the use of probiotics in inflammatory bowel disease, pancreatitis, liver transplantation, and various uses in diarrhea. When using probiotics, one must be cautious of the sometime overzealous claims that are commonly made when dealing with medical foods. As we begin to appreciate the degree of complexity that our indigenous microbial population has on health, it is only then that we can begin to understand the importance in disease. In the arena of probiotics, numerous fundamental questions remain unanswered. PMID:16207661

  12. Species-specific real-time PCR assay for the detection of Streptococcus suis from clinical specimens.

    PubMed

    Srinivasan, Velusamy; McGee, Lesley; Njanpop-Lafourcade, Berthe-Marie; Moïsi, Jennifer; Beall, Bernard

    2016-06-01

    A real-time polymerase chain reaction was developed to detect all known strains of Streptococcus suis. The assay was highly specific, and sensitivity was <10 copies/assay for S. suis detection from clinical samples. PMID:27041105

  13. 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

  14. 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

  15. Regional brain atrophy development is related to specific aspects of clinical dysfunction in multiple sclerosis.

    PubMed

    Jasperse, Bas; Vrenken, Hugo; Sanz-Arigita, Ernesto; de Groot, Vincent; Smith, Stephen M; Polman, Chris H; Barkhof, Frederik

    2007-11-15

    Brain atrophy in multiple sclerosis (MS) is thought to reflect irreversible tissue damage leading to persistent clinical deficit. Little is known about the rate of atrophy in specific brain regions in relation to specific clinical deficits. We determined the displacement of the brain surface between two T1-weighted MRI images obtained at baseline and after a median follow-up time of 2.2 years for 79 recently diagnosed, mildly disabled MS patients. Voxel- and cluster-wise permutation-based statistics were used to identify brain regions in which atrophy development was significantly related to Expanded Disability Status Scale (EDSS), Timed Walk Test (TWT), Paced Auditory Serial Addition Test (PASAT) and 9-Hole Peg Test (HPT). Clusters were considered significant at a corrected cluster-wise p-value of 0.05. Worse EDSS change-score and worse follow-up EDSS were related to atrophy development of periventricular and brainstem regions and right-sided parietal, occipital and temporal regions. Worse PASAT at follow-up was significantly related to atrophy of the ventricles. A worse TWT change-score and worse follow-up TWT were exclusively related to atrophy around the ventricles and of the brainstem. Worse HPT change-score and worse follow-up HPT of either arm were significantly related to the atrophy of widely distributed peripheral regions, as well as atrophy of periventricular and brainstem regions. Our findings suggest that decline in ambulatory function is related to atrophy of central brain regions exclusively, whereas decline in neurologically more complex tasks for coordinated hand function is related to atrophy of both central and peripheral brain regions. PMID:17889567

  16. 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. PMID:26491036

  17. Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.

    PubMed

    Roux, A; Bendib Le Lan, I; Holifanjaniaina, S; Thomas, K A; Hamid, A M; Picard, C; Grenet, D; De Miranda, S; Douvry, B; Beaumont-Azuar, L; Sage, E; Devaquet, J; Cuquemelle, E; Le Guen, M; Spreafico, R; Suberbielle-Boissel, C; Stern, M; Parquin, F

    2016-04-01

    In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis. PMID:26845386

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

    PubMed Central

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

    2015-01-01

    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. PMID:26491036

  19. Incidence and Clinical Significance of De Novo Donor Specific Antibodies after Kidney Transplantation

    PubMed Central

    Panagiotellis, Konstantinos; Iniotaki, Aliki; Boletis, John N.

    2013-01-01

    Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients. PMID:24348683

  20. 2016 Focused Update: Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations.

    PubMed

    Guazzi, Marco; Arena, Ross; Halle, Martin; Piepoli, Massimo F; Myers, Jonathan; Lavie, Carl J

    2016-06-14

    In the past several decades, cardiopulmonary exercise testing (CPX) has seen an exponential increase in its evidence base. The growing volume of evidence in support of CPX has precipitated the release of numerous scientific statements by societies and associations. In 2012, the European Association for Cardiovascular Prevention & Rehabilitation and the American Heart Association developed a joint document with the primary intent of redefining CPX analysis and reporting in a way that would streamline test interpretation and increase clinical application. Specifically, the 2012 joint scientific statement on CPX conceptualized an easy-to-use, clinically meaningful analysis based on evidence-vetted variables in color-coded algorithms; single-page algorithms were successfully developed for each proposed test indication. Because of an abundance of new CPX research in recent years and a reassessment of the current algorithms in light of the body of evidence, a focused update to the 2012 scientific statement is now warranted. The purposes of this update are to confirm algorithms included in the initial scientific statement not requiring revision, to propose revisions to algorithms included in the initial scientific statement, to propose new algorithms based on emerging scientific evidence, to further clarify the application of oxygen consumption at ventilatory threshold, to describe CPX variables with an emerging scientific evidence base, to describe the synergistic value of combining CPX with other assessments, to discuss personnel considerations for CPX laboratories, and to provide recommendations for future CPX research. PMID:27143685

  1. The specificity of emotional switching in borderline personality disorder in comparison to other clinical groups.

    PubMed

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

    2016-04-01

    In an attempt to better understand the nature of emotion dysregulation in the daily lives of persons with a borderline personality disorder (BPD), Houben et al. (2016) 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 2 samples by comparing BPD patients (N = 43 in sample 1; N = 81 in sample 2) to patients with bulimia nervosa (N = 20), 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 2 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 characterizing a range of disorders with mood disturbances. PMID:26882282

  2. Approaches for monitoring of non virus-specific and virus-specific T-cell response in solid organ transplantation and their clinical applications.

    PubMed

    Calarota, Sandra A; Aberle, Judith H; Puchhammer-Stöckl, Elisabeth; Baldanti, Fausto

    2015-09-01

    Opportunistic viral infections are still a major complication following solid organ transplantation. Immune monitoring may allow the identification of patients at risk of infection and, eventually, the modulation of immunosuppressive strategies. Immune monitoring can be performed using virus-specific and non virus-specific assays. This article describes and summarizes the pros and cons of the different technical approaches. Among the assays based on non virus-specific antigens, the enumeration of T-cell subsets, the quantification of cytokines and chemokines and the quantification of intracellular adenosine triphosphate following mitogen stimulation are described and their clinical applications to determine the risk for viral infection are discussed. In addition, current specific methods available for monitoring viral-specific T-cell responses are summarized, such as peptide-MHC multimer staining, intracellular cytokine staining, enzyme-linked immunospot and virus-specific IFN-γ ELISA assays, and their clinical applications to determine the individual risk for opportunistic viral infections with human cytomegalovirus, Epstein-Barr virus and polyoma BK virus are discussed. The standardization of the procedure, the choice of the antigen(s) and the criteria to define cut-off values for positive responses are needed for some of these approaches before their implementation in the clinic. Nevertheless, immune monitoring combined with virological monitoring in transplant recipients is increasingly regarded as a helpful tool to identify patients at risk of infection as well as to assess treatment efficacy. PMID:26305832

  3. 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 Central

    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. PMID:23865056

  4. Specific and Rapid Detection of Mycobacterium tuberculosis Complex in Clinical Samples by Polymerase Chain Reaction

    PubMed Central

    Singh, Anamika; Kashyap, Vijendra Kumar

    2012-01-01

    Background. Tuberculosis, a global health problem and highly prevalent in India, has always been a serious problem with respect to definitive diagnosis. Polymerase chain reaction (PCR) techniques are now widely used for early detection and species differentiation of mycobacteria, but mostly with their own limitations. We aim to detect and differentiate Mycobacterium tuberculosis (Mtb) infections by choosing appropriate target sequences, ideally present in all mycobacterial species (MTB complex) and absent in others. Methods. Amplification of three target sequences from unrelated genes, namely, hsp 65 (165 bp), dnaJ (365 bp), and insertion element IS 6110 (541 bp) by PCR was carried out in clinical samples from suspected cases of tuberculosis/ mycobacterioses and healthy controls. Results. The sensitivity of this method ranged from 73.33% to 84.61%, and the specificity was 80%. The PCR method was significantly better (P = 0.03 and P = 0.009) than both smear and culture methods. Conclusion. Our trimarker-based PCR method could specifically detect M. tuberculosis and MTB complex infection from that of major pathogenic NTM and nonpathogenic mycobacteria. This method, by well distinguishing between MTB complex and NTM, presented a fast and accurate method to detect and diagnose mycobacterial infections more efficiently and could thereby help in better patient management particularly considering the increase in mycobacterial infections due to emergence of NTM over the past decades. PMID:23093958

  5. 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. PMID:26621418

  6. 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. PMID:24952238

  7. The future of cardiovascular clinical research in North America and beyond-addressing challenges and leveraging opportunities through unique academic and grassroots collaborations.

    PubMed

    Roe, Matthew T; Mahaffey, Kenneth W; Ezekowitz, Justin A; Alexander, John H; Goodman, Shaun G; Hernandez, Adrian; Temple, Tracy; Berdan, Lisa; Califf, Robert M; Harrington, Robert A; Peterson, Eric D; Armstrong, Paul W

    2015-06-01

    Recent developments have highlighted the challenges facing cardiovascular clinical research in global contemporary practice, particularly in North America, including shifting priorities for drug development targets, increasing regulatory requirements, and expensive operational approaches for conducting randomized clinical trials. Nonetheless, emerging trends such as the consolidation of practices and hospitals into integrated health systems, the integration of electronic health records from thousands of practices into large data repositories to support prospective research studies, and streamlined operational approaches such as registry-based trials and risk-based monitoring have created numerous opportunities to disrupt the clinical research paradigm. Within this context, academic research organizations around the globe, particularly a strengthened collaboration of 3 established academic research organizations in North America, are uniquely positioned to promote and develop grassroots collaborations across all types of clinical practices, to delineate successful solutions to obstacles that limit clinical research initiatives, and to guide the future of cardiovascular research in the global research environment. PMID:26027610

  8. A Scalable Architecture for Incremental Specification and Maintenance of Procedural and Declarative Clinical Decision-Support Knowledge

    PubMed Central

    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. PMID:21611137

  9. Effects of pathogen-specific clinical mastitis on probability of conception in Holstein dairy cows.

    PubMed

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

    2014-11-01

    The objective of this study was to estimate the effects of pathogen-specific clinical mastitis (CM), occurring in different weekly intervals before or after artificial insemination (AI), on the probability of conception in Holstein cows. Clinical mastitis occurring in weekly intervals from 6 wk before until 6 wk after AI was modeled. The first 4 AI in a cow's lactation were included. The following categories of pathogens were studied: Streptococcus spp. (comprising Streptococcus dysgalactiae, Streptococcus uberis, and other Streptococcus spp.); Staphylococcus aureus; coagulase-negative staphylococci (CNS); Escherichia coli; Klebsiella spp.; cases with CM signs but no bacterial growth (above the level that can be detected from our microbiological procedures) observed in the culture sample and cases with contamination (≥ 3 pathogens in the sample); and other pathogens [including Citrobacter, yeasts, Trueperella pyogenes, gram-negative bacilli (i.e., gram-negative organisms other than E. coli, Klebsiella spp., Enterobacter, and Citrobacter), Corynebacterium bovis, Corynebacterium spp., Pasteurella, Enterococcus, Pseudomonas, Mycoplasma, Prototheca, and others]. Other factors included in the model were parity (1, 2, 3, 4 and higher), season of AI (winter, spring, summer, autumn), day in lactation of first AI, farm, and other non-CM diseases (retained placenta, metritis, ketosis, displaced abomasum). Data from 90,271 AI in 39,361 lactations in 20,328 cows collected from 2003/2004 to 2011 from 5 New York State dairy farms were analyzed in a generalized linear mixed model with a Poisson distribution. The largest reductions in probability of conception were associated with CM occurring in the week before AI or in the 2 wk following AI. Escherichia coli and Klebsiella spp. had the greatest adverse effects on probability of conception. The probability of conception for a cow with any combination of characteristics may be calculated based on the parameter estimates. These

  10. Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model

    PubMed Central

    Leone, Dario; Camporeale, Carlo; Bruno, Giulia; Ridolfi, Luca; Veglio, Franco; Milan, Alberto

    2016-01-01

    Introduction Current evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice. Aim The aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics. Methods A total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study. Results Model-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2(-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed. Conclusion In conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures. PMID:27010562

  11. 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

  12. Age-specific Serum Prostate Specific Antigen Ranges Among Apparently Healthy Nigerian Men Without Clinical Evidence of Prostate Cancer

    PubMed Central

    Ikuerowo, SO; Ajala, MO; Abolarinwa, AA; Omisanjo, OA

    2016-01-01

    Introduction: Serum prostate specific antigen (PSA) levels increase with age and varies among different races and communities. The study was aimed at defining the age-specific reference ranges of serum PSA in our environment. Methods: We evaluated the relationship between age and serum PSA levels and the age-specific reference ranges of serum PSA among civil servants in Lagos, who underwent routine medical checkups. Criteria for inclusion were men who have no lower urinary tract symptoms, normal digital rectal examination and serum PSA ≤ 20 ng/ml. SPSS Statistic 21 was used for data evaluation and the mean, median, 95th percentile PSA levels were estimated. Pearson's correlation was used to examine the relationship, and P < 0.05 was considered significant. Results: 4032 men met the criteria for inclusion in the evaluation. The mean age was 51.6 (range 40–70) years, and there was a strong correlation between serum PSA levels and age (r = 0.097, P < 0.001). PSA ranges of 0–2.5, >2.5–4.0, >4.0–10, and >10 ng/ml were found in 3218 (80%), 481 (12%), 284 (7%), and 52 (1%) men, respectively. The mean, median and the 95th percentile PSA for the overall group were 1.84, 1.33, and 5.2 ng/ml respectively. However the 95th percentile PSA levels for men aged 40–49, 50–59, and 60–70 years were 4.78, 5.47, and 8.93 ng/ml respectively. Conclusion: The age-specific PSA levels among Nigerian men for each age group is higher than what was described for men in the Western world. These reference ranges of serum PSA should be considered for men aged ≥40 years in our environment. PMID:27013850

  13. Specific antidotes against direct oral anticoagulants: A comprehensive review of clinical trials data.

    PubMed

    Tummala, Ramyashree; Kavtaradze, Ana; Gupta, Anjan; Ghosh, Raktim Kumar

    2016-07-01

    The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulation's tests affected, available clinical and preclinical data, and the need for phase III and IV studies. PMID:27082776

  14. 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

  15. [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

  16. Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

    PubMed Central

    Cuadrado, Antonio; San Segundo, David; López-Hoyos, Marcos; Crespo, Javier; Fábrega, Emilio

    2015-01-01

    Antibody-mediated rejection (AMR) caused by donor-specific anti-human leukocyte antigen antibodies (DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This “immune-tolerance” liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant (LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class II human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional anti-rejection therapy, can allow a rational approach to this threat. PMID:26494958

  17. Performance and specificity rates in the Test of Memory Malingering: an investigation into pediatric clinical populations.

    PubMed

    Loughan, Ashlee R; Perna, Robert

    2014-01-01

    Symptom validity tests are becoming standard as an effort measure during pediatric neuropsychological assessment. An important component of symptom validity test use is understanding limitations of these measures and how select clinical groups may have difficulty with them. Research has begun to clarify the limits of the Test of Memory Malingering (TOMM) with diverse childhood diagnoses. This study compared TOMM scores of children (N = 86) classified with common childhood disorders. Findings suggest that a substantial proportion of children performed below the recommended cutoff score of 45 on Trial 2 and attained varied specificity rates. This included children with conduct disorders (85%), affective disorders (92%), traumatic brain injury (83%), attention-deficit hyperactivity disorder (93%), learning disabilities (100%), and pervasive developmental disorder (88%). The group with the most children scoring below the cutoff was children with intellectual disabilities (76%). This finding is consistent with some of the adult research suggesting that very limited cognitive ability may compromise TOMM performance. Caution may be necessary when drawing conclusions about test-taking effort based on the recommended TOMM cutoff scores when evaluating children with disabilities. PMID:24236938

  18. Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay.

    PubMed

    Kovalevskaya, G; Birken, S; Kakuma, T; Schlatterer, J; O'Connor, J F

    1999-01-01

    We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made. PMID:9895340

  19. Trauma in silico: Individual-specific mathematical models and virtual clinical populations.

    PubMed

    Brown, David; Namas, Rami A; Almahmoud, Khalid; Zaaqoq, Akram; Sarkar, Joydeep; Barclay, Derek A; Yin, Jinling; Ghuma, Ali; Abboud, Andrew; Constantine, Gregory; Nieman, Gary; Zamora, Ruben; Chang, Steven C; Billiar, Timothy R; Vodovotz, Yoram

    2015-04-29

    Trauma-induced critical illness is driven by acute inflammation, and elevated systemic interleukin-6 (IL-6) after trauma is a biomarker of adverse outcomes. We constructed a multicompartment, ordinary differential equation model that represents a virtual trauma patient. Individual-specific variants of this model reproduced both systemic inflammation and outcomes of 33 blunt trauma survivors, from which a cohort of 10,000 virtual trauma patients was generated. Model-predicted length of stay in the intensive care unit, degree of multiple organ dysfunction, and IL-6 area under the curve as a function of injury severity were in concordance with the results from a validation cohort of 147 blunt trauma patients. In a subcohort of 98 trauma patients, those with high-IL-6 single-nucleotide polymorphisms (SNPs) exhibited higher plasma IL-6 levels than those with low IL-6 SNPs, matching model predictions. Although IL-6 could drive mortality in individual virtual patients, simulated outcomes in the overall cohort were independent of the propensity to produce IL-6, a prediction verified in the 98-patient subcohort. In silico randomized clinical trials suggested a small survival benefit of IL-6 inhibition, little benefit of IL-1β inhibition, and worse survival after tumor necrosis factor-α inhibition. This study demonstrates the limitations of extrapolating from reductionist mechanisms to outcomes in individuals and populations and demonstrates the use of mechanistic simulation in complex diseases. PMID:25925680

  20. Addressing neurological disorders with neuromodulation.

    PubMed

    Oluigbo, Chima O; Rezai, Ali R

    2011-07-01

    Neurological disorders are becoming increasingly common in developed countries as a result of the aging population. In spite of medications, these disorders can result in progressive loss of function as well as chronic physical, cognitive, and emotional disability that ultimately places enormous emotional and economic on the patient, caretakers, and the society in general. Neuromodulation is emerging as a therapeutic option in these patients. Neuromodulation is a field, which involves implantable devices that allow for the reversible adjustable application of electrical, chemical, or biological agents to the central or peripheral nervous system with the objective of altering its functioning with the objective of achieving a therapeutic or clinically beneficial effect. It is a rapidly evolving field that brings together many different specialties in the fields of medicine, materials science, computer science and technology, biomedical, and neural engineering as well as the surgical or interventional specialties. It has multiple current and emerging indications, and an enormous potential for growth. The main challenges before it are in the need for effective collaboration between engineers, basic scientists, and clinicians to develop innovations that address specific problems resulting in new devices and clinical applications. PMID:21193369

  1. 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

  2. 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…

  3. HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial

    PubMed Central

    Bart, Pierre-Alexandre; Huang, Yunda; Karuna, Shelly T.; Chappuis, Samuel; Gaillard, Julien; Kochar, Nidhi; Shen, Xiaoying; Allen, Mary A.; Ding, Song; Hural, John; Liao, Hua-Xin; Haynes, Barton F.; Graham, Barney S.; Gilbert, Peter B.; McElrath, M. Juliana; Montefiori, David C.; Tomaras, Georgia D.; Pantaleo, Giuseppe; Frahm, Nicole

    2014-01-01

    BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5–vectored (rAd5-vectored) vaccine. METHODS. NYVAC-B included HIV-1 clade B Gag-Pol-Nef and gp120, while rAd5 included HIV-1 clade B Gag-Pol and clades A, B, and C gp140. Eighty Ad5-seronegative subjects were randomized to receive 2 × NYVAC-B followed by 1 × 1010 PFU rAd5 (NYVAC/Ad5hi); 1 × 108 PFU rAd5 followed by 2 × NYVAC-B (Ad5lo/NYVAC); 1 × 109 PFU rAd5 followed by 2 × NYVAC-B (Ad5med/NYVAC); 1 × 1010 PFU rAd5 followed by 2 × NYVAC-B (Ad5hi/NYVAC); or placebo. Immune responses were assessed 2 weeks after the final vaccination. Intracellular cytokine staining measured T cells producing IFN-γ and/or IL-2; cross-clade and epitope-specific binding antibodies were determined; and neutralizing antibodies (nAbs) were assessed with 6 tier 1 viruses. RESULTS. CD4+ T cell response rates ranged from 42.9% to 93.3%. NYVAC/Ad5hi response rates (P ≤ 0.01) and magnitudes (P ≤ 0.03) were significantly lower than those of other groups. CD8+ T cell response rates ranged from 65.5% to 85.7%. NYVAC/Ad5hi magnitudes were significantly lower than those of other groups (P ≤ 0.04). IgG response rates to the group M consensus gp140 were 89.7% for NYVAC/Ad5hi and 21.4%, 84.6%, and 100% for Ad5lo/NYVAC, Ad5med/NYVAC, and Ad5hi/NYVAC, respectively, and were similar for other vaccine proteins. Overall nAb responses were low, but aggregate responses appeared stronger for Ad5med/NYVAC and Ad5hi/NYVAC than for NYVAC/Ad5hi. CONCLUSIONS. rAd5 prime followed by NYVAC boost is superior to the reverse regimen for both vaccine

  4. 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.

  5. Investigating the clinical usefulness of the Social Responsiveness Scale (SRS) in a tertiary level, autism spectrum disorder specific assessment clinic.

    PubMed

    Aldridge, Fiona J; Gibbs, Vicki M; Schmidhofer, Katherine; Williams, Megan

    2012-02-01

    The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems. PMID:21516433

  6. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations

    PubMed Central

    Hoa, S.; Hudson, M.; Troyanov, Y.; Proudman, S.; Walker, J.; Stevens, W.; Nikpour, M.; Assassi, S.; Mayes, M.D.; Wang, M.; Baron, M.; Fritzler, M.J.

    2016-01-01

    Abstract Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc. An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated. Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies. This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc. PMID:27583908

  7. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations.

    PubMed

    Hoa, S; Hudson, M; Troyanov, Y; Proudman, S; Walker, J; Stevens, W; Nikpour, M; Assassi, S; Mayes, M D; Wang, M; Baron, M; Fritzler, M J

    2016-08-01

    Autoantibodies directed against the Ku autoantigen are present in systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the absence of other SSc-specific antibodies. The aim of this study was to assess the clinical correlates of single-specificity anti-Ku in SSc.An international (Canada, Australia, USA, Mexico) cohort of 2140 SSc subjects was formed, demographic and clinical variables were harmonized, and sera were tested for anti-Ku using a line immunoassay. Associations between single-specificity anti-Ku antibodies (i.e., in isolation of other SSc-specific antibodies) and outcomes of interest, including myositis, ILD, and survival, were investigated.Twenty-four (1.1%) subjects had antibodies against Ku, and 13 (0.6%) had single-specificity anti-Ku antibodies. Subjects with single-specificity anti-Ku antibodies were more likely to have ILD (58% vs 34%), and to have increased creatine kinase levels (>3× normal) at baseline (11% vs 1%) and during follow-up (10% vs 2%). No difference in survival was noted in subjects with and without single-specificity anti-Ku antibodies.This is the largest cohort to date focusing on the prevalence and disease characteristics of single-specificity anti-Ku antibodies in subjects with SSc. These results need to be interpreted with caution in light of the small sample. International collaboration is key to understanding the clinical correlates of uncommon serological profiles in SSc. PMID:27583908

  8. Prevalence of Legionella-specific IgG and IgM antibody in a dental clinic population.

    PubMed

    Fotos, P G; Westfall, H N; Snyder, I S; Miller, R W; Mutchler, B M

    1985-12-01

    This study was undertaken to determine the frequency of Legionella infection in a dental clinic setting. Serum samples from 270 dental clinic personnel were evaluated using an enzyme-linked immunosorbent assay to detect Legionella-specific IgM and IgG antibodies. The pooled-species whole-cell-antigen preparation used in these assays was derived from six Legionella pneumophila strains and one strain each from Legionella bozemanii and Legionella micdadei. Significant levels of IgG and IgM antibodies were found in 20% and 16%, respectively, of the samples. This compares with 8% and 10%, respectively, for a randomly selected non-clinical group from the region (P less than 0.005). Samples from clinic personnel with significant IgG titers (greater than 1:128) were also evaluated for activity to each of the eight single-species antigens, with the following results: L. pneumophila, 45% (combined six strains); L. micdadei, 37%; and L. bozemanii, 18%. Comparing individuals' "years spent in the clinic environment" with the incidence of significant antibody levels strongly suggests that the risk of Legionella infection increases proportionately with increased clinic exposure time (P less than 0.05). Analysis of these data implies that Legionella may be present in the dental clinic environment, thus creating an increased risk for clinical personnel or patients. PMID:3865949

  9. Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

    PubMed Central

    Oliphant, Raymond; Horgan, Paul G; Morrison, David S; McMillan, Donald C

    2015-01-01

    Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P<0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P<0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival. PMID:25487740

  10. Clinical Markers for Specific Language Impairment in Italian: The Contribution of Clitics and Non-Word Repetition

    ERIC Educational Resources Information Center

    Bortolini, Umberta; Arfe, Barbara; Caselli, Cristina M.; Degasperi, Luisa; Deevy, Patricia; Leonard, Laurence B.

    2006-01-01

    Background: The discovery of clinical markers for specific language impairment (SLI) in children can assist in the accurate identification of children with this disorder, and in a description of the disorder's phenotype for genetic study. One challenge to this type of research is the fact that languages vary in the most salient symptoms of SLI.…

  11. 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

  12. 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

  13. Clinical relevance is associated with allergen-specific wheal size in skin prick testing

    PubMed Central

    Haahtela, T; Burbach, G J; Bachert, C; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bousquet-Rouanet, L; Bousquet, P J; Bresciani, M; Bruno, A; Canonica, G W; Darsow, U; Demoly, P; Durham, S R; Fokkens, W J; Giavi, S; Gjomarkaj, M; Gramiccioni, C; Kowalski, M L; Losonczy, G; Orosz, M; Papadopoulos, N G; Stingl, G; Todo-Bom, A; von Mutius, E; Köhli, A; Wöhrl, S; Järvenpää, S; Kautiainen, H; Petman, L; Selroos, O; Zuberbier, T; Heinzerling, L M

    2014-01-01

    Background Within a large prospective study, the Global Asthma and Allergy European Network (GA2LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. Objective To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. Methods The GA2LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Results Depending on the allergen, from 40% (blatella) to 87–89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. Conclusion These ‘reading keys’ for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. PMID:24283409

  14. Responsiveness of the Dermatology-specific Quality of Life (DSQL) instrument to treatment for acne vulgaris in a placebo-controlled clinical trial.

    PubMed

    Anderson, R; Rajagopalan, R

    1998-12-01

    The Dermatology-specific Quality of Life (DSQL) instrument is a new tool which has been developed to address the effects of skin disease and its treatment on physical and social functioning and self-perceptions. Previous reports have demonstrated its cross-sectional validity. The current study examines the DSQL's responsiveness to 12 weeks of acne treatment in a placebo-controlled randomized clinical trial. The DSQL change scores were moderately correlated (r = 0.18 to 0.37) with treatment efficacy parameters including: dermatologist's rating of improvement of acne and a skin irritation score, and highly correlated with patient's global rating of acne severity. Within treatment groups, the DSQL discriminated clinically meaningful changes associated with small and moderate effect sizes. The DSQL total score showed statistically significant differences on nearly all comparisons with placebo. The DSQL dimension scores were sensitive to the most effective therapy compared to placebo. Responsiveness benchmarks are provided for small and moderatesized treatment effects. As a comprehensive instrument, the DSQL is a practical and psychometrically sound tool for use in clinical trials in dermatology. PMID:10097621

  15. High sensitivity and specificity of clinical microscopy in rural health facilities in western Kenya under an external quality assurance program.

    PubMed

    Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

    2014-09-01

    Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. PMID:24935953

  16. 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

  17. 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. PMID:27277430

  18. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:23994378

  20. 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. PMID:23994378

  1. Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

    PubMed Central

    Légaré, France; Moher, David; Elwyn, Glyn; LeBlanc, Annie; Gravel, Karine

    2007-01-01

    Background The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. Methods For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD. Results Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some

  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. 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…

  4. 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…

  5. Awards and Addresses Summary

    PubMed Central

    2008-01-01

    Each year at the annual ASHG meeting, addresses are given in honor of the society and a number of award winners. A summary of each of these addresses is given below. On the next pages, we have printed the Presidential Address and the addresses for the William Allan Award. The other addresses, accompanied by pictures of the speakers, can be found at www.ashg.org.

  6. 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

  7. 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. PMID:26220795

  8. Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations

    PubMed Central

    2013-01-01

    Background Detecting mutations in disease genes by full gene sequence analysis is common in clinical diagnostic laboratories. Sanger dideoxy terminator sequencing allows for rapid development and implementation of sequencing assays in the clinical laboratory, but it has limited throughput, and due to cost constraints, only allows analysis of one or at most a few genes in a patient. Next-generation sequencing (NGS), on the other hand, has evolved rapidly, although to date it has mainly been used for large-scale genome sequencing projects and is beginning to be used in the clinical diagnostic testing. One advantage of NGS is that many genes can be analyzed easily at the same time, allowing for mutation detection when there are many possible causative genes for a specific phenotype. In addition, regions of a gene typically not tested for mutations, like deep intronic and promoter mutations, can also be detected. Results Here we use 20 previously characterized Sanger-sequenced positive controls in disease-causing genes to demonstrate the utility of NGS in a clinical setting using standard PCR based amplification to assess the analytical sensitivity and specificity of the technology for detecting all previously characterized changes (mutations and benign SNPs). The positive controls chosen for validation range from simple substitution mutations to complex deletion and insertion mutations occurring in autosomal dominant and recessive disorders. The NGS data was 100% concordant with the Sanger sequencing data identifying all 119 previously identified changes in the 20 samples. Conclusions We have demonstrated that NGS technology is ready to be deployed in clinical laboratories. However, NGS and associated technologies are evolving, and clinical laboratories will need to invest significantly in staff and infrastructure to build the necessary foundation for success. PMID:23418865

  9. Clinical Specificities in Obesity Care: The Transformations and Dissolution of 'Will' and 'Drives'

    PubMed

    Vogel, Else

    2014-06-17

    Public debate about who or what is to blame for the rising rates of obesity and overweight shifts between two extreme opinions. The first posits overweight as the result of a lack of individual will, the second as the outcome of bodily drives, potentially triggered by the environment. Even though apparently clashing, these positions are in fact two faces of the same liberal coin. When combined, drives figure as a complication on the road to health, while a strong will should be able to counter obesity. Either way, the body's propensity to eat is to be put under control. Drawing on fieldwork in several obesity clinics and prevention sites in the Netherlands, this paper first traces how this 'logic of control' presents itself in clinical practices targeted at overweight people, and then goes on to explore how these practices move beyond that logic. Using the concepts of 'will' and 'drives' as analytical tools, I sketch several modes of ordering reality in which bodies, subjects, food and the environment are configured in different ways. In this way it appears that in clinical practices the terms found in public discourse take on different meanings and may even lose all relevance. The analysis reveals a richness of practiced ideals. The paper argues, finally, that making visible these alternative modes of ordering opens up a space for normative engagements with obesity care that move beyond the logic of control and its critiques. PMID:24934390

  10. 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

  11. Magnetic content addressable memories

    NASA Astrophysics Data System (ADS)

    Jiang, Zhenye

    Content Addressable Memories are designed with comparison circuits built into every bit cell. This parallel structure can increase the speed of searching from O(n) (as with Random Access Memories) to O(1), where n is the number of entries being searched. The high cost in hardware limits the application of CAM within situations where higher searching speed is extremely desired. Spintronics technology can build non-volatile Magnetic RAM with only one device for one bit cell. There are various technologies involved, like Magnetic Tunnel Junctions, off-easy-axis programming method, Synthetic Anti-Ferromagnetic tri-layers, Domain Wall displacement, Spin Transfer Torque tri-layers and etc. With them, particularly the Tunnel Magneto-Resistance variation in MTJ due to difference in magnetization polarity of the two magnets, Magnetic CAM can be developed with reduced hardware cost. And this is demonstrated by the discussion in this dissertation. Six MCAM designs are discussed. In the first design, comparand (C), local information (S) and their complements are stored into 4 MTJs connected in XOR gate pattern. The other five designs have one or two stacks for both information storage and comparison, and full TMR ratio can be taken advantage of. Two challenges for the five are specifically programming C without changing S and selectively programming a cell out of an array. The solutions to specific programming are: by confining the programming field for C in a ring structure design; by using field programming and spin polarized current programming respectively for C and S in the SAF+DW and SAF+STT tri-layer design; by making use of the difference in thresholds between direct mode and toggle mode switching in the SAF+SAF design. The problem of selective programming is addressed by off-easy-axis method and by including SAF tri-layers. Cell with STT tri-layers for both C and S can completely avoid the problems of specific and selective programming, but subject to the limit of

  12. 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

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

    PubMed

    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

  14. Pulmonary Hemodynamics Simulations Before Stage 2 Single Ventricle Surgery: Patient-Specific Parameter Identification and Clinical Data Assessment.

    PubMed

    Arbia, Gregory; Corsini, Chiara; Baker, Catriona; Pennati, Giancarlo; Hsia, Tain-Yen; Vignon-Clementel, Irene E

    2015-09-01

    Single ventricle heart defects involve pathologies in which the heart has only one functional pumping chamber. In these conditions, treatment consists of three staged procedures. At stage 1 pulmonary flow is provided through an artificial shunt from the systemic circulation. Representative hemodynamics models able to explore different virtual surgical options can be built based on pre-operative imaging and patient data. In this context, the specification of boundary conditions is necessary to compute pressure and flow in the entire domain. However, these boundary conditions are rarely the measured variables. Moreover, to take into account the rest of the circulation outside of the three-dimensional modeled domain, a number of reduced order models exist. A simplified method is presented to iteratively, but automatically, tune reduced model parameters from hemodynamic data clinically measured before stage 2 surgery. Patient-specific local hemodynamics around the distal systemic-to-pulmonary shunt anastomosis and the connected pulmonary arteries are also analyzed. Multi-scale models of pre-stage 2 single ventricle patients are developed, including a 3D model of shunt-pulmonary connection and a number of pulmonary arteries. For each pulmonary outlet a total downstream resistance is identified, consistent with measured flow split and pressures. Target pressures such as minimum, maximum or average over one or both lungs are considered, depending on the clinical measurement. When possible, both steady and pulsatile identifications are performed. The methodology is demonstrated with six patient-specific models: the clinical target data are well-matched, except for one case where clinical data were subsequently found inconsistent. Inhomogeneous pressure, swirling blood flow patterns and very high wall shear stress 3D maps highlight similarities and differences among patients. Steady and pulsatile tuning results are similar. This work demonstrates (1) how to use routine

  15. 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…

  16. 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...

  17. Considering specific clinical features as evidence of pathogenic copy number variants.

    PubMed

    Preiksaitiene, Egle; Molytė, Alma; Kasnauskiene, Jurate; Ciuladaite, Zivile; Utkus, Algirdas; Patsalis, Philippos C; Kučinskas, Vaidutis

    2014-05-01

    Since the introduction of high-resolution microarray technologies, it has become apparent that structural chromosomal rearrangements can lead to a wide variety of clinical manifestations, including developmental delay/intellectual disability (DD/ID). It has been shown previously that the diagnostic yield of genome-wide array-based identification of submicroscopic alterations in patients with ID varies widely and depends on the patient selection criteria. More attempts have recently been made to define the phenotypic clues of pathogenic copy number variants (CNVs). The aim of this study was to investigate a well-phenotyped cohort of patients with DD/ID and determine whether certain clinical features may serve as indicators for pathogenic CNVs. A retrospective analysis was conducted for patients with DD/ID (n = 211) who were tested using genome-wide chromosomal microarray technologies and a review of the clinical data was performed. Pathogenic CNVs were detected in 29 patients. In comparison with individuals who had normal molecular karyotyping results (n = 182), malformations of the musculoskeletal system; congenital malformations of the CNS (particularly hydrocephalus and congenital malformations of the corpus callosum); minor anomalies of the eye, face, and neck subgroup (particularly downward-slanting palpebral fissures, minor anomalies of the ear, and micrognathia); brachydactyly; and umbilical hernia were more common in patients with chromosomal alterations. A multivariate logistic regression analysis allowed the identification of three independent pathogenic CNV predictors: congenital malformations of the corpus callosum, minor anomalies of the ear, and brachydactyly. Insights into the chromosomal phenotype may help to increase the diagnostic yield of microarray technologies and sharpen the distinction between chromosomal alterations and other conditions. PMID:24535828

  18. Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO

    PubMed Central

    Kitley, Joanna; Woodhall, Mark; Leite, M. Isabel; Palace, Jackie; Waters, Patrick

    2015-01-01

    Objective: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. Methods: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody–positive NMO/NMO spectrum disorder. Results: The AQP4 M23 (40–61,440) and AQP4 M1 (<20–20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1–192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. Conclusion: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies. PMID:26140280

  19. Selection of disease-specific biomarkers by integrating inflammatory mediators with clinical informatics in AECOPD patients: a preliminary study.

    PubMed

    Chen, Hong; Song, Zhenju; Qian, Mengjia; Bai, Chunxue; Wang, Xiangdong

    2012-06-01

    Systemic inflammation is a major factor influencing the outcome and quality of patient with chronic obstructive pulmonary disease (COPD) and acute exacerbations (AECOPD). Because of the inflammatory complexity, a great challenge is still confronted to optimize the identification and validation of disease-specific biomarkers. This study aimed at developing a new protocol of specific biomarker evaluation by integrating proteomic profiles of inflammatory mediators with clinical informatics in AECOPD patients, understand better their function and signal networks. Plasma samples were collected from healthy non-smokers or patients with stable COPD (sCOPD) or AECOPD on days 1 and 3 of the admission and discharging day (day 7-10). Forty chemokines were measured using a chemokine multiplex antibody array. Clinical informatics was achieved by a Digital Evaluation Score System (DESS) for assessing severity of patients. Chemokine data was compared among different groups and its correlation with DESS scores was performed by SPSS software. Of 40 chemokines, 30 showed significant difference between sCOPD patients and healthy controls, 16 between AECOPD patients and controls and 13 between AECOPD patients and both sCOPD and controls, including BTC, IL-9, IL-18Bpa, CCL22,CCL23, CCL25, CCL28, CTACK, LIGHT, MSPa, MCP-3, MCP-4 and OPN. Of them, some had significant correlation with DESS scores. There is a disease-specific profile of inflammatory mediators in COPD and AECOPD patients which may have a potential diagnostics together with clinical informatics of patients. Our preliminary study suggested that integration of proteomics with clinical informatics can be a new way to validate and optimize disease-special biomarkers. PMID:21883889

  20. Specific Primers for Rapid Detection of Microsporum audouinii by PCR in Clinical Samples▿

    PubMed Central

    Roque, H. D.; Vieira, R.; Rato, S.; Luz-Martins, M.

    2006-01-01

    This report describes application of PCR fingerprinting to identify common species of dermatophytes using the microsatellite primers M13, (GACA)4, and (GTG)5. The initial PCR analysis rendered a specific DNA fragment for Microsporum audouinii, which was cloned and sequenced. Based on the sequencing data of this fragment, forward (MA_1F) and reverse (MA_1R) primers were designed and verified by PCR to establish their reliability in the diagnosis of M. audouinii. These primers produced a singular PCR band of 431 bp specific only to strains and isolates of M. audouinii, based on a global test of 182 strains/isolates belonging to 11 species of dermatophytes. These findings indicate these primers are reliable for diagnostic purposes, and we recommend their use in laboratory analysis. PMID:17005755

  1. Type- and subtype-specific detection of influenza viruses in clinical specimens by rapid culture assay.

    PubMed

    Ziegler, T; Hall, H; Sánchez-Fauquier, A; Gamble, W C; Cox, N J

    1995-02-01

    A rapid culture assay which allows for the simultaneous typing and subtyping of currently circulating influenza A(H1N1), A(H3N2), and B viruses in clinical specimens was developed. Pools of monoclonal antibodies (MAbs) against influenza A and B viruses and MAbs HA1-71 and HA2-76, obtained by immunizing mice with the denatured hemagglutinin subfragments HA1 and HA2 of influenza virus A/Victoria/3/75, were used for immunoperoxidase staining of antigens in infected MDCK cells. MAb HA1-71 reacted exclusively with influenza A viruses of the H3 subtype, while MAb HA2-76 reacted with subtypes H1, H3, H4, H6, H8, H9, H10, H11, and H12, as determined with 78 human, 4 swine, and 10 avian influenza virus reference strains subtyped by the hemagglutination inhibition test. To determine if the technique can be used as a rapid diagnostic test, 263 known influenza virus-positive frozen nasal or throat swabs were inoculated into MDCK cells. After an overnight incubation, the cells were fixed and viral antigens were detected by immunoperoxidase staining. Influenza A viruses of the H1 and H3 subtypes were detected in 31 and 113 specimens, respectively. The subtypes of 10 influenza A virus-positive specimens could not be determined because they contained too little virus. Influenza B viruses were detected in 84 specimens, and 25 specimens were negative. We conclude that this assay is a rapid, convenient, non-labor-intensive, and relatively inexpensive test for detecting, typing, and subtyping influenza viruses in clinical specimens. PMID:7714186

  2. Factors affecting the response to the specific treatment of several forms of clinical anestrus in high producing dairy cows.

    PubMed

    López-Gatius, F; Mirzaei, A; Santolaria, P; Bech-Sàbat, G; Nogareda, C; García-Ispierto, I; Hanzen, Ch; Yániz, J L

    2008-06-01

    This study was designed to examine estrous response rates to the therapeutic treatment of clinical anestrus in high producing dairy cows and to identify the factors that could affect these rates. Cows with silent ovulation (Subestrus group), cystic ovarian disease (Cyst group) or ovarian hypofunction (OH group) were given specific treatment for their disorder. Data were derived from 1764 treatments in cows producing a mean of 45.4 kg of milk upon treatment including: 889 subestrous cows, 367 cystic cows and 508 cows with ovarian hypofunction. Cows showing estrus following treatment exhibited a similar pregnancy rate to cows attaining natural estrus used as reference: 33% (337/1006) and 35% (626/1796), respectively. No significant differences in pregnancy rates were observed among the Subestrus, Cyst and OH groups (34% (196/571), 34% (44/130), 32% (97/305), respectively. Based on the odds ratio, an estrous response for all groups was less likely to occur in cows that had suffered previous anestrus, compared to cows that were anestrous for the first time, whereas the likelihood of an estrous response increased in cows treated after 90 days in milk. Our results indicate that previous anestrus and a late stage of lactation can have a negative and positive effect, respectively, on the estrous response to the specific treatment of clinical anestrus shown by high producing dairy cows. Treatment targeted at each type of clinical anestrus can render similar pregnancy rates to those shown by cows in natural estrus. PMID:18359070

  3. 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

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

    PubMed

    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

  5. [Oral glucocorticoid-induced psychiatric side-effects: focus on clinical specificities, incidence, risk factors and treatment].

    PubMed

    Ricoux, A; Guitteny-Collas, M; Sauvaget, A; Delvot, P; Pottier, P; Hamidou, M; Vanelle, J-M

    2013-05-01

    Oral glucocorticoids have been used for several decades and psychiatric side-effects may occur. This review will discuss relevant data of the clinical specificities, the incidence, the risk factors for the occurrence of these episodes and the preventive and curative medications of these episodes. We performed a literature review by using PubMed database. We selected and discussed articles and studies with high standard of evidence. The occurrence of psychiatric symptoms is quite frequent. The varying intensity of clinical features ranges from minor signs (impregnation) to acute psychotic episodes which may occur from 5 to 30% of patients. Affective symptoms or disorders are the most prominent clinical features. Delirium may occur and suicidal risk could be increased. The significant predictive factors are prednisone dosage more than 40 mg/day, particularly weight-based dosage, and a history of psychiatric disorders. When a reduced dosage of glucocorticoids is not sufficient to control the symptomatology, curative medication is mainly based on atypical antipsychotics such as olanzapine. Studies about neuropsychiatric complications of glucocorticoids present various and heterogeneous results. Further prospective clinical studies should be based on a close cooperation between physicians and consultation liaison psychiatrists. This collaboration is required for an optimized management of the patient who receive glucocorticoids. PMID:23374903

  6. 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

  7. Expression of fibroblast specific protein-1 in pleural tuberculosis and its clinical biological significance

    PubMed Central

    2014-01-01

    Background Fibroblast specific protein-1 (S100A4) is related with many fibrotic diseases, but its role in the pathogenesis of pleural fibrosis has not been fully elucidated. Then we aim to investigate the expression and effect of fibroblast specific protein-1 (S100A4) in pleural tuberculosis and, subsequently, pleural fibrosis. Methods The expression of S100A4 in pleura was examined in 30 patients with pleural tuberculosis and 5 control (disease-free) patients by immunohistochemistry using the streptavidin-peroxidase (S-P) conjugated method. Results The expression of S100A4 in pleura was mainly distributed in the nucleus and cytoplasm of fibroblasts and vascular endothelial cells, and the positive rate was 90.0% (27 out of 30 patients with pleural tuberculosis). There were no expressions of S100A4 in the control group. In the pleura of all 30 patients with pleural tuberculosis, S100A4 had a higher expression in the two- to eight-week duration of the disease. Conclusions S100A4 plays an important role in the phenotypic transformation of pleural mesothelial cells and the development of pleural fibrosis. PMID:24885536

  8. [The immunological mechanisms contributing to the clinical efficacy of allergen specific immunotherapy (SIT) in allergic diseases].

    PubMed

    Asher, Ilan; Mahlab-Guri, Keren; Sthoeger, Zev

    2013-09-01

    The prevalence of allergic diseases has increased dramatically in the western world. In the last 2 decades, the frequency of asthma and allergic rhinitis has doubled. Allergen specific immunotherapy [SIT] has been used successfully for more than 100 years for the treatment of allergic disorders. Allergen SIT provides not only symptomatic relief, but it is potentially curative. The immunologic mechanisms of allergen SIT include all parts of the immune system. Regulatory T cells (TR1, Treg), have a major pivotal role in the success of immunotherapy. Along with the regulatory T cells, elevated suppressor cytokines (IL-10), suppression of TH2 cells, increasing titer of specific IgG4 and gradual decline in the number and function of basophils and mast cells also contribute to the success of the treatment (SIT). The above immune mechanisms are connected and related to each other acting at different times with the treatment with SIT. In this review we focused on the current knowledge and understanding of the different immune mechanisms which are involved in the success of SIT. PMID:24364093

  9. [The specific clinical features of acute sensorineural loss of hearing associated with vertigo].

    PubMed

    Pal'chun, V T; Guseva, A L; Levina, Yu V; Chistov, S D

    2016-01-01

    The objective of the present study was to estimate the prevalence of vertigo and to determine the type of the lesion of the vestibular analyzer in the patients presenting with acute sensorineural loss of hearing (ASNLH). The secondary objective was to evaluate the possibility of the restoration of the auditory thresholds. The results of the examination and treatment of 94 patients suffering from ASNLH are presented. It was shown that the development of acute sensorineural loss of hearing was accompanied by unilateral peripheral vestibulopathy in 22.3% of the patients. In 5.3% of these cases, dizziness could be attributed to benign paroxysmal positional vertigo and canalolythias is of the posterior semicircular canal on the side of hearing impairment. It is concluded that the presence of the clinical signs of lesions of the vestibular analyzer and peripheral vestibular dysfunction in the form of latent spontaneous nystagmus without gaze fixation and/or asymmetric nystagmus with unilateral weakness in the caloric test is a negative prognostic factor for the restoration of the auditory thresholds in the patients presenting with acute sensorineural loss of hearing. PMID:26977560

  10. 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. PMID:24215524

  11. 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. PMID:22858988

  12. 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. PMID:27095254

  13. Rectal microbicides: clinically relevant approach to the design of rectal specific placebo formulations

    PubMed Central

    2011-01-01

    Background The objective of this study is to identify the critical formulation parameters controlling distribution and function for the rectal administration of microbicides in humans. Four placebo formulations were designed with a wide range of hydrophilic characteristics (aqueous to lipid) and rheological properties (Newtonian, shear thinning, thermal sensitive and thixotropic). Aqueous formulations using typical polymers to control viscosity were iso-osmotic and buffered to pH 7. Lipid formulations were developed from lipid solvent/lipid gelling agent binary mixtures. Testing included pharmaceutical function and stability as well as in vitro and in vivo toxicity. Results The aqueous fluid placebo, based on poloxamer, was fluid at room temperature, thickened and became shear thinning at 37°C. The aqueous gel placebo used carbopol as the gelling agent, was shear thinning at room temperature and showed a typical decrease in viscosity with an increase in temperature. The lipid fluid placebo, myristyl myristate in isopropyl myristate, was relatively thin and temperature independent. The lipid gel placebo, glyceryl stearate and PEG-75 stearate in caprylic/capric triglycerides, was also shear thinning at both room temperature and 37°C but with significant time dependency or thixotropy. All formulations showed no rectal irritation in rabbits and were non-toxic using an ex vivo rectal explant model. Conclusions Four placebo formulations ranging from fluid to gel in aqueous and lipid formats with a range of rheological properties were developed, tested, scaled-up, manufactured under cGMP conditions and enrolled in a formal stability program. Clinical testing of these formulations as placebos will serve as the basis for further microbicide formulation development with drug-containing products. PMID:21385339

  14. 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

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

    PubMed

    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

  16. Site-specific IGFBP-1 hyper-phosphorylation in fetal growth restriction: clinical and functional relevance.

    PubMed

    Abu Shehab, Majida; Khosravi, Javad; Han, Victor K M; Shilton, Brian H; Gupta, Madhulika B

    2010-04-01

    Phosphorylation enhances IGFBP-1 binding to IGF-I, thereby limiting the bioavailability of IGF-I that may be important in fetal growth. Our goal in this study was to determine whether changes in site-specific IGFBP-1 phosphorylation were unique to fetal growth restriction. To establish a link, we compared IGFBP-1 phosphorylation (sites and degree) in amniotic fluid from FGR (N = 10) and controls (N = 12). The concentration of serine phosphorylated IGFBP-1 showed a negative correlation with birth weight in FGR (P = 0.049). LC-MS/MS analysis revealed all four previously identified phosphorylation sites (Ser98, Ser101, Ser119, and Ser169) to be common to FGR and control groups. Relative phosphopeptide intensities (LC-MS) between FGR and controls demonstrated 4-fold higher intensity for Ser101 (P = 0.026), 7-fold for Ser98/Ser101 (P = 0.02), and 23-fold for Ser169 (P = 0.002) in the FGR group. Preliminary BIAcore data revealed 4-fold higher association and 1.7-fold lower dissociation constants for IGFBP-1/IGF-I in FGR. A structural model of IGFBP-1 bound to IGF-I indicates that all the phosphorylation sites are on relatively mobile regions of the IGFBP-1 sequence. Residues Ser98, Ser101, and Ser169 are close to structured regions that are involved in IGF-I binding and, therefore, could potentially make direct contact with IGF-I. On the other hand, residue Ser119 is in the middle of the unstructured linker that connects the N- and C-terminal domains of IGFBP-1. The model is consistent with the assumption that residues Ser98, Ser101, and Ser169 could directly interact with IGF-I, and therefore phosphorylation at these sites could change IGF-I interactions. We suggest that site-specific increase in IGFBP-1 phosphorylation limits IGF-I bioavailability, which directly contributes to the development of FGR. This study delineates the potential role of higher phosphorylation of IGFBP-1 in FGR and provides the basis to substantiate these findings with larger sample size. PMID

  17. 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

  18. 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

    2016-01-01

    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 [(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. PMID:27601313

  19. 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. PMID:1273628

  20. 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

  1. Clinical Characteristics of Adults with Chronic Rhinosinusitis and Specific Antibody Deficiency

    PubMed Central

    Kashani, Sara; Carr, Tara F.; Grammer, Leslie C.; Schleimer, Robert P.; Hulse, Kathryn E.; Kato, Atsushi; Kern, Robert C.; Conley, David B.; Chandra, Rakesh K.; Tan, Bruce K.; Peters, Anju T.

    2015-01-01

    Background Specific antibody deficiency (SAD) involves a deficient response to a polysaccharide vaccine in the setting of normal IgG levels and chronic infections. Patients with chronic rhinosinusitis (CRS) are often evaluated for SAD. There is limited data describing patients with CRS and SAD. Objective To better characterize the role of SAD in CRS. Methods We reviewed electronic records of adults with CRS who were evaluated for immunodeficiency with quantitative immunoglobulin levels and pre- and post-antibody titers to a pneumococcal polysaccharide vaccine (PPV). Results 14 pneumococcal serotypes were determined in 239 subjects from 2002–2009. 64 subjects had adequate protective titers of 1.3 μg/mL or higher in 7 or more serotypes out of the 14 serotypes checked. 56 (23%) had less than 7 protective titers post-PPV and were diagnosed with SAD. 119 subjects had an adequate response to the vaccine with 7 or more serotypes being higher than 1.3 μg/mL (>50% response) and were characterized as “responders”. Subjects with SAD received more antibiotic courses relative to responders in the two years following immunization (3.19 ± 2.64 vs. 2.19 ± 2.24, p<0.05). Ten of 56 subjects (17.9%) with SAD received immunoglobulin (Ig) replacement therapy. Subjects receiving Ig had fewer numbers of protective pneumococcal titers post PPV and had more pneumonia (40.0%) versus subjects with SAD not receiving Ig (10.9%). Conclusions Of 239 CRS patients with normal IgG levels evaluated for immunodeficiency, 56 (23.4%) had SAD. A majority of patients with SAD may not need Ig replacement however, a subset of patients with SAD benefit from Ig replacement. PMID:25609325

  2. Governing healthcare: finding meaning in a clinical practice guideline for the management of non-specific low back pain.

    PubMed

    Wilson, Nicky; Pope, Catherine; Roberts, Lisa; Crouch, Robert

    2014-02-01

    Clinical practice guidelines produced by NICE - the National Institute for Health and Care Excellence - are seen as key mechanisms to regulate and standardise UK healthcare practice, but their development is known to be problematic, and their adoption and uptake variable. Examining what a guideline or health policy means to different audiences, and how it means something to those communities, provides new insight about interpretive discourses. In this paper we present a micro-analysis of the response of healthcare professionals to publication of a single NICE guideline in 2009 which proposed a re-organisation of professional services for chronic non-specific low back pain. Adopting an interpretive approach, we seek to understand both the meaning of the guideline and the socio-political events associated with it. Drawing on archived policy documents related to the development and publication of the guideline, texts published in professional journals and on web-sites, and semi-structured interview data from professionals associated with the debate, we identify a key discourse that positions the management of chronic non-specific low back pain within physician jurisdiction. We examine the emergence of this discourse through policy-related symbolic artifacts taking the form of specific languages, objects and acts. This discourse effectively resisted and displaced the service reorganisation proposed by the guideline and, in so doing, ensured medical hegemony within practice and professional organisations concerned with the management of non-specific low back pain. PMID:24565151

  3. 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

  4. 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

    2015-01-01

    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

  5. [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. PMID:25680645

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

    PubMed Central

    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. PMID:26609369

  7. Patient-specific modelling of abdominal aortic aneurysms: The influence of wall thickness on predicted clinical outcomes.

    PubMed

    Conlisk, Noel; Geers, Arjan J; McBride, Olivia M B; Newby, David E; Hoskins, Peter R

    2016-06-01

    Rupture of abdominal aortic aneurysms (AAAs) is linked to aneurysm morphology. This study investigates the influence of patient-specific (PS) AAA wall thickness on predicted clinical outcomes. Eight patients under surveillance for AAAs were selected from the MA(3)RS clinical trial based on the complete absence of intraluminal thrombus. Two finite element (FE) models per patient were constructed; the first incorporated variable wall thickness from CT (PS_wall), and the second employed a 1.9mm uniform wall (Uni_wall). Mean PS wall thickness across all patients was 1.77±0.42mm. Peak wall stress (PWS) for PS_wall and Uni_wall models was 0.6761±0.3406N/mm(2) and 0.4905±0.0850N/mm(2), respectively. In 4 out of 8 patients the Uni_wall underestimated stress by as much as 55%; in the remaining cases it overestimated stress by up to 40%. Rupture risk more than doubled in 3 out of 8 patients when PS_wall was considered. Wall thickness influenced the location and magnitude of PWS as well as its correlation with curvature. Furthermore, the volume of the AAA under elevated stress increased significantly in AAAs with higher rupture risk indices. This highlights the sensitivity of standard rupture risk markers to the specific wall thickness strategy employed. PMID:27056256

  8. 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. PMID:27151293

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

    PubMed

    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

    2015-01-01

    We have been 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 the present 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 better 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 from the anus. When the luminal side of the colon was washed with phosphate-buffered saline, most of the nanospheres were flushed. However, fluorescence persisted in areas where 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 remained bound to tumors even after vigorous washing. The nanospheres nonspecifically bound to normal mucosa were easily removed through mild washing. These results indicate that the nanospheres combined with colonoscopy, will be a clinically-valuable diagnostic tool for early-stage primary colon carcinoma. PMID:24976331

  10. Preclinical and Clinical Performance of the Efoora Test, a Rapid Test for Detection of Human Immunodeficiency Virus-Specific Antibodies

    PubMed Central

    Arens, Max Q.; Mundy, Linda M.; Amsterdam, Daniel; Barrett, J. Tom; Bigg, Dan; Bruckner, David; Hanna, Bruce; Prince, Harry; Purington, Timothy; Hanna, Todd; Hewitt, Ross; Kalinka, Carolyn; Koppes, Thomas; Maxwell, Sarz; Moe, Ardis; Doymaz, Mehmet; Poulter, Melinda; Saber-Tehrani, Maryam; Simard, Lorenzo; Wilkins-Carmody, Donna; Vidaver, John; Berger, Cheryl; Davis, Alan H.; Alzona, Mortimer T.

    2005-01-01

    Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized

  11. Imaging, virtual planning, design, and production of patient-specific implants and clinical validation in craniomaxillofacial surgery.

    PubMed

    Dérand, Per; Rännar, Lars-Erik; Hirsch, Jan-M

    2012-09-01

    The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes(®), Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and

  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. Using pathology-specific laboratory profiles in Clinical Pathology to reduce inappropriate test requesting: two completed audit cycles

    PubMed Central

    2012-01-01

    Background Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Methods Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs’ request forms. Results Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p < 0.001); 2) the provisional diagnosis on the request forms was 52.8% in the trial district and 42% in the control district (P < 0.001); 3) the decrease of the number of tests on each request form was much more marked in the trial district (8.73 vs. 10.77; p < 0.001). Conclusions The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the

  14. Addressivity in cogenerative dialogues

    NASA Astrophysics Data System (ADS)

    Hsu, Pei-Ling

    2014-03-01

    Ashraf Shady's paper provides a first-hand reflection on how a foreign teacher used cogens as culturally adaptive pedagogy to address cultural misalignments with students. In this paper, Shady drew on several cogen sessions to showcase his journey of using different forms of cogens with his students. To improve the quality of cogens, one strategy he used was to adjust the number of participants in cogens. As a result, some cogens worked and others did not. During the course of reading his paper, I was impressed by his creative and flexible use of cogens and at the same time was intrigued by the question of why some cogens work and not others. In searching for an answer, I found that Mikhail Bakhtin's dialogism, especially the concept of addressivity, provides a comprehensive framework to address this question. In this commentary, I reanalyze the cogen episodes described in Shady's paper in the light of dialogism. My analysis suggests that addressivity plays an important role in mediating the success of cogens. Cogens with high addressivity function as internally persuasive discourse that allows diverse consciousnesses to coexist and so likely affords productive dialogues. The implications of addressivity in teaching and learning are further discussed.

  15. 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

  16. Efficacy of a piglet-specific commercial inactivated vaccine against Porcine circovirus type 2 in clinical field trials

    PubMed Central

    Han, Kiwon; Seo, Hwi Won; Oh, Yeonsu; Park, Changhoon; Kang, Ikjae; Jang, Hyun; Chae, Chanhee

    2013-01-01

    The efficacy of a piglet-specific inactivated Porcine circovirus type 2 (PCV2) vaccine was evaluated with clinical field trials, as recommended by the Republic of Korea’s Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected on the basis of their history of postweaning multisystemic wasting syndrome. On each farm 60, 1-week-old pigs were randomly allocated to 1 of 2 treatment groups: vaccination at 1 and 3 wk of age or no vaccination. The 2-dose schedule of vaccination with inactivated PCV2 vaccine improved the average daily weight gain from birth to 16 wk of age, the PCV2 load in the blood, and the frequency and severity of lymph node lesions. Inactivated PCV2 vaccine seems to be very effective in controlling PCV2 infection under field conditions. PMID:24101803

  17. Clinical and radiological signs of ABPA associated with airways infection with Aspergillus in the absence of specific IgE.

    PubMed

    Sunzini, F; Barbato, C; Canofari, C; Lugari, L; Perricone, R; Bergamini, A

    2016-09-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus that mainly affects patients with asthma. For diagnosis, elevated serum IgE level are needed according to Greenberger and Patterson criteria. We report a case of 43 years-old woman who developed ABPA with productive cough, fever and radiological findings of multiple confluent areas of consolidation in both upper lobes. Laboratory tests showed elevated peripheral eosinophil counts (9.3 x 10(3)/ml). In bronchial washing A. galactomannans and A. Fumigatus were isolated, although we found normal levels of serum IgE, and the absence of serum IgG and IgE antibodies to Aspergillus and A. galactomannans. In conclusion, clinical and radiological signs of ABPA can be associated with Aspergillus infection also in the absence of a specific serum antibody reaction. PMID:27608478

  18. 3D-manufactured patient-specific models of congenital heart defects for communication in clinical practice: feasibility and acceptability

    PubMed Central

    Biglino, Giovanni; Capelli, Claudio; Wray, Jo; Schievano, Silvia; Leaver, Lindsay-Kay; Khambadkone, Sachin; Giardini, Alessandro; Derrick, Graham; Jones, Alexander; Taylor, Andrew M

    2015-01-01

    Objectives To assess the communication potential of three-dimensional (3D) patient-specific models of congenital heart defects and their acceptability in clinical practice for cardiology consultations. Design This was a questionnaire-based study in which participants were randomised into two groups: the ‘model group’ received a 3D model of the cardiac lesion(s) being discussed during their appointment, while the ‘control group’ had a routine visit. Setting Outpatient clinic, cardiology follow-up visits. Participants 103 parents of children with congenital heart disease were recruited (parental age: 43±8 years; patient age: 12±6 years). In order to have a 3D model made, patients needed to have a recent cardiac MRI examination; this was the crucial inclusion criterion. Interventions Questionnaires were administered to the participants before and after the visits and an additional questionnaire was administered to the attending cardiologist. Main outcome measures Rating (1–10) for the liking of the 3D model, its usefulness and the clarity of the explanation received were recorded, as well as rating (1–10) of the parental understanding and their engagement according to the cardiologist. Furthermore, parental knowledge was assessed by asking them to mark diagrams, tick keywords and provide free text answers. The duration of consultations was recorded and parent feedback collected. Results Parents and cardiologists both found the models to be very useful and helpful in engaging the parents in discussing congenital heart defects. Parental knowledge was not associated with their level of education (p=0.2) and did not improve following their visit. Consultations involving 3D models lasted on average 5 min longer (p=0.02). Conclusions Patient-specific models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment. However, in

  19. Clinical Efficacy of a Specifically Targeted Antimicrobial Peptide Mouth Rinse: Targeted Elimination of Streptococcus mutans and Prevention of Demineralization

    PubMed Central

    Sullivan, R.; Santarpia, P.; Lavender, S.; Gittins, E.; Liu, Z.; Anderson, M.H.; He, J.; Shi, W.; Eckert, R.

    2011-01-01

    Background/Aims Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective ‘targeting region’ comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a ‘killing region’ consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. Methods In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. Results and Conclusions C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic. PMID:21860239

  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. PMID:25743760

  2. 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. PMID:25239539

  3. A patient-specific aperture system with an energy absorber for spot scanning proton beams: Verification for clinical application

    SciTech Connect

    Yasui, Keisuke; Toshito, Toshiyuki; Omachi, Chihiro; Kibe, Yoshiaki; Hayashi, Kensuke; Shibata, Hiroki; Tanaka, Kenichiro; Nikawa, Eiki; Asai, Kumiko; Shimomura, Akira; Kinou, Hideto; Isoyama, Shigeru; Mizoe, Jun-etsu; Fujii, Yusuke; Takayanagi, Taisuke; Hirayama, Shusuke; Nagamine, Yoshihiko; Shibamoto, Yuta; Komori, Masataka

    2015-12-15

    Purpose: In the authors’ proton therapy system, the patient-specific aperture can be attached to the nozzle of spot scanning beams to shape an irradiation field and reduce lateral fall-off. The authors herein verified this system for clinical application. Methods: The authors prepared four types of patient-specific aperture systems equipped with an energy absorber to irradiate shallow regions less than 4 g/cm{sup 2}. The aperture was made of 3-cm-thick brass and the maximum water equivalent penetration to be used with this system was estimated to be 15 g/cm{sup 2}. The authors measured in-air lateral profiles at the isocenter plane and integral depth doses with the energy absorber. All input data were obtained by the Monte Carlo calculation, and its parameters were tuned to reproduce measurements. The fluence of single spots in water was modeled as a triple Gaussian function and the dose distribution was calculated using a fluence dose model. The authors compared in-air and in-water lateral profiles and depth doses between calculations and measurements for various apertures of square, half, and U-shaped fields. The absolute doses and dose distributions with the aperture were then validated by patient-specific quality assurance. Measured data were obtained by various chambers and a 2D ion chamber detector array. Results: The patient-specific aperture reduced the penumbra from 30% to 70%, for example, from 34.0 to 23.6 mm and 18.8 to 5.6 mm. The calculated field width for square-shaped apertures agreed with measurements within 1 mm. Regarding patient-specific aperture plans, calculated and measured doses agreed within −0.06% ± 0.63% (mean ± SD) and 97.1% points passed the 2%-dose/2 mm-distance criteria of the γ-index on average. Conclusions: The patient-specific aperture system improved dose distributions, particularly in shallow-region plans.

  4. Clinical Markers in Italian-Speaking Children with and without Specific Language Impairment: A Study of Non-Word and Real Word Repetition as Predictors of Grammatical Ability

    ERIC Educational Resources Information Center

    Dispaldro, Marco; Leonard, Laurence B.; Deevy, Patricia

    2013-01-01

    Background: In many languages a weakness in non-word repetition serves as a useful clinical marker of specific language impairment (SLI) in children. However, recent work in Italian has shown that the repetition of real words may also have clinical utility. For young typically developing Italian children, real word repetition is more predictive of…

  5. 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

  6. 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

  7. 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

  8. Evaluating health information technology: provider satisfaction with an HIV-specific, electronic clinical management and reporting system.

    PubMed

    Magnus, Manya; Herwehe, Jane; Andrews, Laura; Gibson, Laura; Daigrepont, Nathan; De Leon, Jordana M; Hyslop, Newton E; Styron, Steven; Wilcox, Ronald; Kaiser, Michael; Butler, Michael K

    2009-02-01

    Health information technology (HIT) offers the potential to improve care for persons living with HIV. Provider satisfaction with HIT is essential to realize benefits, yet its evaluation presents challenges. An HIV-specific, electronic clinical management and reporting system was implemented in Louisiana's eight HIV clinics, serving over 7500. A serial cross-sectional survey was administered at three points between April 2002 and July 2005; qualitative methods were used to augment quantitative. Multivariable methods were used to characterize provider satisfaction. The majority of the sample (n = 196; T1 = 105; T2 = 46; T3 = 45) was female (80.0%), between ages of 25 and 50 years (68.3%), frequent providers at that clinic (53.7% more than 4 days per week), and had been at the same clinic for a year or more (85.0%). Improvements in satisfaction were observed in patient tracking ( p < 0.05), distribution of educational materials ( p < 0.04), and belief that electronic systems improve care ( p < 0.05). Provider self-reports of time to complete critical functions decreased for all tasks, two significantly so. Time (in minutes) to find current CD4 count decreased at each time point (mean 3.9 [standard deviation {SD} 5.8], 2.9 [2.3], 2.1 [2.6], p>0.05), current viral load decreased at each time point (mean 4.0 [SD 5.6], 2.9 [2.5], 1.8 [2.6], p = 0.08], current antiretroviral status decreased at each time point (mean 3.9 [SD 4.7], 2.9 [3.7], 1.5 [1.1], p < 0.04), history of antiretroviral use decreased at each time point (mean 15.1 [SD 21.9], 6.0 [5.4], 5.4 [7.2], p < 0.04]. Time savings were realized, averaging 16.1 minutes per visit ( p < 0.04). Providers were satisfied with HIT in multiple domains, and significant time savings were realized. PMID:19133750

  9. 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.

  10. 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…

  11. Address of the President

    ERIC Educational Resources Information Center

    Ness, Frederic W.

    1976-01-01

    The president of the Association of American Colleges addresses at the 62nd annual meeting the theme of the conference: "Looking to the Future--Liberal Education in a Radically Changing Society." Contributions to be made by AAC are examined. (LBH)

  12. 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…

  13. Space sciences - Keynote address

    NASA Technical Reports Server (NTRS)

    Alexander, Joseph K.

    1990-01-01

    The present status and projected future developments of the NASA Space Science and Applications Program are addressed. Emphasis is given to biochemistry experiments that are planned for the Space Station. Projects for the late 1990s which will study the sun, the earth's magnetosphere, and the geosphere are briefly discussed.

  14. A highly specific q-RT-PCR assay to address the relevance of the JAK2WT and JAK2V617F expression levels and control genes in Ph-negative myeloproliferative neoplasms.

    PubMed

    Fantasia, Francesca; Di Capua, Emma Nora; Cenfra, Natalia; Pessina, Gloria; Mecarocci, Sergio; Rago, Angela; Cotroneo, Ettore; Busanello, Anna; Equitani, Francesco; Lo-Coco, Francesco; Nervi, Clara; Cimino, Giuseppe

    2014-04-01

    In Ph- myeloproliferative neoplasms, the quantification of the JAK2V617F transcripts may provide some advantages over the DNA allele burden determination. We developed a q-RT-PCR to assess the JAK2WT and JAK2V617F mRNA expression in 105 cases (23 donors, 13 secondary polycythemia, 22 polycythemia vera (PV), 38 essential thrombocythemia (ET), and 9 primary myelofibrosis (PMF)). Compared with the standard allele-specific oligonucleotide (ASO)-PCR technique, our assay showed a 100 % concordance rate detecting the JAK2V617F mutation in 22/22 PV (100 %), 29/38 (76.3 %) ET, and 5/9 (55.5 %) PMF cases, respectively. The sensitivity of the assay was 0.01 %. Comparing DNA and RNA samples, we found that the JAK2V617F mutational ratios were significantly higher at the RNA level both in PV (p = 0.005) and ET (p = 0.001) samples. In PV patients, JAK2WT expression levels positively correlated with the platelets (PLTs) (p = 0.003) whereas a trend to negative correlation was observed with the Hb levels (p = 0.051). JAK2V617F-positive cases showed the lowest JAK2WT and ABL1 mRNA expression levels. In all the samples, the expression pattern of beta-glucoronidase (GUSB) was more homogeneous than that of ABL1 or β2 microglobulin (B2M). Using GUSB as normalizator gene, a significant increase of the JAK2V617F mRNA levels was seen in two ET patients at time of progression to PV. In conclusion, the proposed q-RT-PCR is a sensitive and accurate method to quantify the JAK2 mutational status that can also show clinical correlations suggesting the impact of the residual amount of the JAK2WT allele on the Ph- MPN disease phenotype. Our observations also preclude the use of ABL1 as a housekeeping gene for these neoplasms. PMID:24173087

  15. Excerpts from keynote address

    SciTech Connect

    Creel, G.C.

    1995-06-01

    Excerpts from the keynote principally address emissions issues in the fossil power industry as related to heat rate improvements. Stack emissions of both sulfur and nitrogen oxides are discussed, and a number of examples are given: (1) PEPCO`s Potomac River Station, and (2) Morgantown station`s NOX reduction efforts. Circulating water emissions are also briefly discussed, as are O & M costs of emission controls.

  16. Holographic content addressable storage

    NASA Astrophysics Data System (ADS)

    Chao, Tien-Hsin; Lu, Thomas; Reyes, George

    2015-03-01

    We have developed a Holographic Content Addressable Storage (HCAS) architecture. The HCAS systems consists of a DMD (Digital Micromirror Array) as the input Spatial Light Modulator (SLM), a CMOS (Complementary Metal-oxide Semiconductor) sensor as the output photodetector and a photorefractive crystal as the recording media. The HCAS system is capable of performing optical correlation of an input image/feature against massive reference data set stored in the holographic memory. Detailed system analysis will be reported in this paper.

  17. Comparative Proteomic Analyses of Avirulent, Virulent, and Clinical Strains of Mycobacterium tuberculosis Identify Strain-specific Patterns*

    PubMed Central

    Jhingan, Gagan Deep; Kumari, Sangeeta; Jamwal, Shilpa V.; Kalam, Haroon; Arora, Divya; Jain, Neharika; Kumaar, Lakshmi Krishna; Samal, Areejit; Rao, Kanury V. S.; Kumar, Dhiraj; Nandicoori, Vinay Kumar

    2016-01-01

    Mycobacterium tuberculosis is an adaptable intracellular pathogen, existing in both dormant as well as active disease-causing states. Here, we report systematic proteomic analyses of four strains, H37Ra, H37Rv, and clinical isolates BND and JAL, to determine the differences in protein expression patterns that contribute to their virulence and drug resistance. Resolution of lysates of the four strains by liquid chromatography, coupled to mass spectrometry analysis, identified a total of 2161 protein groups covering ∼54% of the predicted M. tuberculosis proteome. Label-free quantification analysis of the data revealed 257 differentially expressed protein groups. The differentially expressed protein groups could be classified into seven K-means cluster bins, which broadly delineated strain-specific variations. Analysis of the data for possible mechanisms responsible for drug resistance phenotype of JAL suggested that it could be due to a combination of overexpression of proteins implicated in drug resistance and the other factors. Expression pattern analyses of transcription factors and their downstream targets demonstrated substantial differential modulation in JAL, suggesting a complex regulatory mechanism. Results showed distinct variations in the protein expression patterns of Esx and mce1 operon proteins in JAL and BND strains, respectively. Abrogating higher levels of ESAT6, an important Esx protein known to be critical for virulence, in the JAL strain diminished its virulence, although it had marginal impact on the other strains. Taken together, this study reveals that strain-specific variations in protein expression patterns have a meaningful impact on the biology of the pathogen. PMID:27151218

  18. Comparing Rapid and Specific Detection of Brucella in Clinical Samples by PCR-ELISA and Multiplex-PCR Method

    PubMed Central

    Mohammad Hasani, Sharareh; Mirnejad, Reza; Amani, Jafar; Vafadar, Mohamad javad

    2016-01-01

    Background: Rapid diagnosis and differentiation of Brucella is of high importance due to the side effects of antibiotics for the treatment of brucellosis. This study aimed to identify and compare PCR-ELISA as a more accurate diagnositc test with other common molecular and serological tests. Methods: In this experimental and sectional study, during March 2014 to Sep 2015, 52 blood samples of suspected patients with clinical symptoms of brucellosis were evaluated in medical centers all over Iran with serum titers higher than 1:80. Using two pairs of specific primers of Brucella abortus, B. melitensis and DIG-dUTP, Fragment IS711 (The common gene fragment in B. melitensis and B. abortus) was amplified. DIG-ELISA was performed using specific probes of these 2 species of Brucella and patterns were subsequently analyzed, then positive responses were compared by detecting gel electrophoresis. Results: PCR-ELISA method detected all 28 samples from 52 positive samples. Its sensitivity was 6.0 pg concentration of genomic DNA of Brucella. In gel electrophoresis method, 22 samples of all positive samples were detected. PCR-ELISA was more efficient than PCR and bacterial culture method at P-value <0.05. Conclusion: PCR-ELISA molecular method is more sensitive than other molecular methods, lack of mutagenic color and also a semi-quantitative ability. This method is more effective and more accurate compared to PCR, serology and culture of bacteria. PCR-ELISA does not have false responses. The limitation of this method is detection of bacteria in the genus compared to Multiplex PCR and Gel Electrophoresis. PMID:27499776

  19. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 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....

  20. 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....

  1. 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

  2. Over- and Undercontrolled Clinic Referral Problems of Jamaican and American Children and Adolescents: The Culture General and the Culture Specific.

    ERIC Educational Resources Information Center

    Lambert, Michael C.; And Others

    1989-01-01

    Studied clinical referrals of two different societies (Jamaica, where Afro-British culture discourages child aggression, and United States, where uncontrolled child behavior appears more accepted) to determine influence of cultural factors in clinical referral patterns. Found significant difference in clinic-referred problems of American and…

  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. 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

  5. Delegate Assembly Address

    ERIC Educational Resources Information Center

    Johnson, Jerry A.

    1976-01-01

    The report on proposed reorganization of the American Occupational Therapy Association details historical developments, demands for change, and a general rationale for reorganization, as well as specific recommendations for action. (GW)

  6. Addressing Environmental Health Inequalities.

    PubMed

    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. Pharmacological levels of Withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    PubMed

    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; Vanden Berghe, Wim

    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. 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

  9. 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.

  10. Bax: Addressed to kill.

    PubMed

    Renault, Thibaud T; Manon, Stéphen

    2011-09-01

    The pro-apoptototic protein Bax (Bcl-2 Associated protein X) plays a central role in the mitochondria-dependent apoptotic pathway. In healthy mammalian cells, Bax is essentially cytosolic and inactive. Following a death signal, the protein is translocated to the outer mitochondrial membrane, where it promotes a permeabilization that favors the release of different apoptogenic factors, such as cytochrome c. The regulation of Bax translocation is associated to conformational changes that are under the control of different factors. The evidences showing the involvement of different Bax domains in its mitochondrial localization are presented. The interactions between Bax and its different partners are described in relation to their ability to promote (or prevent) Bax conformational changes leading to mitochondrial addressing and to the acquisition of the capacity to permeabilize the outer mitochondrial membrane. PMID:21641962

  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 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

  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

    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. PMID:26224434

  13. 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. PMID:24000836

  14. [Quality Management and Quality Specifications of Laboratory Tests in Clinical Studies--Challenges in Pre-Analytical Processes in Clinical Laboratories].

    PubMed

    Ishibashi, Midori

    2015-01-01

    The cost, speed, and quality are the three important factors recently indicated by the Ministry of Health, Labour and Welfare (MHLW) for the purpose of accelerating clinical studies. Based on this background, the importance of laboratory tests is increasing, especially in the evaluation of clinical study participants' entry and safety, and drug efficacy. To assure the quality of laboratory tests, providing high-quality laboratory tests is mandatory. For providing adequate quality assurance in laboratory tests, quality control in the three fields of pre-analytical, analytical, and post-analytical processes is extremely important. There are, however, no detailed written requirements concerning specimen collection, handling, preparation, storage, and shipping. Most laboratory tests for clinical studies are performed onsite in a local laboratory; however, a part of laboratory tests is done in offsite central laboratories after specimen shipping. As factors affecting laboratory tests, individual and inter-individual variations are well-known. Besides these factors, standardizing the factors of specimen collection, handling, preparation, storage, and shipping, may improve and maintain the high quality of clinical studies in general. Furthermore, the analytical method, units, and reference interval are also important factors. It is concluded that, to overcome the problems derived from pre-analytical processes, it is necessary to standardize specimen handling in a broad sense. PMID:26524888

  15. 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

  16. 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…

  17. Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specific cell-permeable peptide inhibitor.

    PubMed

    Martins, Leila R; Perera, Yasser; Lúcio, Paulo; Silva, Maria G; Perea, Silvio E; Barata, João T

    2014-01-15

    Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identification of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efficacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL. PMID:24473900

  18. The Alberta Health Technology Assessment (HTA) Ambassador Program: The Development of a Contextually Relevant, Multidisciplinary Clinical Practice Guideline for Non-specific Low Back Pain: A Review

    PubMed Central

    Peter, Aaron; Taenzer, Paul

    2011-01-01

    ABSTRACT Purpose: To describe the development of a contextually relevant multidisciplinary clinical practice guideline (CPG) for non-specific low back pain (LBP) and to discuss its value to the management of LBP and the practice of physiotherapy. Method: To mitigate an identified knowledge gap for Alberta primary-care practitioners in the management of non-specific LBP, a collaborative process was developed to engage multidisciplinary health care providers in designing a primary-care CPG for non-specific LBP. A comprehensive review of published LBP guidelines identified the seven highest-quality CPGs; these were used to inform a multidisciplinary guideline development group (GDG) as they developed the CPG. Results: The GDG constructed a CPG for non-specific LBP along with point-of-care decision-support and patient-education tools. Conclusions: The Ambassador Program on Low Back Pain worked with front-line clinicians from across Alberta to review the best available evidence in developing a CPG responsive to the Alberta context. This CPG is intervention specific and provides a wide range of primary-care practitioners with the best available evidence to inform their clinical decisions in managing non-specific LBP. PMID:22654233

  19. [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). PMID:25377675

  20. 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...

  1. 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…

  2. 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. PMID:25033032

  3. 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.

  4. [Chronic cytomegalovirus infection that present specific clinical course--a case of a boy with common variable immunodeficiency].

    PubMed

    Wada, Y; Sato, T; Kitajima, H; Kubo, M

    1995-04-01

    We describe an 8-year-old boy with CVID and chronic CMV infection. Although at onset he was diagnosed as IgA deficiency, 4 years after his clinical manifestations because compatible to CVID. During his clinical course he had suffered from various disorders as follows; AIHA, interstitial pneumonia, hemophagocytic syndrome, chronic gastroenterocolitis and so forth. At the age of 8 the PCR of CMV-DNA of biopsy specimen from colon, lung and bone marrow were confirmed to be positive. Hematological examinations revealed abnormal cellular immunity such as decreased CD 4/8 ratio with increased HLA- DR+ CD 8+ T cell, decrease of absolute blood lymphocytes count and reduced response of lymphocytes to blastogenetic agents. These findings brought us to diagnose him as having CVID complicated with chronic CMV infection. This case gives us some impact to speculate what role CMV infection plays in CVID, Whose etiology is unknown. PMID:7553061

  5. Developing a Physiotherapy-Specific Preliminary Clinical Decision-Making Tool for Oxygen Titration: A Modified Delphi Study

    PubMed Central

    Duong, Michelle; Bertin, Kendra; Henry, Renee; Singh, Deepti; Timmins, Nolla; Brooks, Dina; Mathur, Sunita

    2014-01-01

    ABSTRACT Purpose: To develop and evaluate a preliminary clinical decision-making tool (CDMT) to assist physiotherapists in titrating oxygen for acutely ill adults in Ontario. Methods: A panel of 14 experienced cardiorespiratory physiotherapists was recruited. Factors relating to oxygen titration were identified using a modified Delphi technique. Four rounds of questionnaires were conducted, during which the goals were to (1) generate factors, (2) reduce factors and debate contentious factors, (3) finalize factors and develop the preliminary CDMT, and (4) evaluate the usability of the tool in a clinical context. Results: The panel reached consensus on a total of 89 factors, which were compiled to create the preliminary CDMT. The global tool reached consensus for sensibility, receiving a mean score of 6/7 on a 7-point Likert-type scale (1=unacceptable; 7=excellent). Five of the nine individual components of evaluation of the tool achieved scores ≥6.0; the remaining four had mean scores between 5.4 and 5.9. Conclusion: This study produced a preliminary CDMT for oxygen titration, which the panel agreed was highly comprehensible and globally sensible. Further research is necessary to evaluate the sensibility and applicability of the tool in a clinical setting. PMID:25125782

  6. Patient-Specific CT-Based Instrumentation versus Conventional Instrumentation in Total Knee Arthroplasty: A Prospective Randomized Controlled Study on Clinical Outcomes and In-Hospital Data

    PubMed Central

    Kotela, Andrzej; Lorkowski, Jacek; Kucharzewski, Marek; Wilk-Frańczuk, Magdalena; Śliwiński, Zbigniew; Frańczuk, Bogusław; Łęgosz, Paweł  ; Kotela, Ireneusz

    2015-01-01

    Total knee arthroplasty (TKA) is a frequently performed procedure in orthopaedic surgery. Recently, patient-specific instrumentation was introduced to facilitate correct positioning of implants. The aim of this study was to compare the early clinical results of TKA performed with patient-specific CT-based instrumentation and conventional technique. A prospective, randomized controlled trial on 112 patients was performed between January 2011 and December 2011. A group of 112 patients who met the inclusion and exclusion criteria were enrolled in this study and randomly assigned to an experimental or control group. The experimental group comprised 52 patients who received the Signature CT-based implant positioning system, and the control group consisted of 60 patients with conventional instrumentation. Clinical outcomes were evaluated with the KSS scale, WOMAC scale, and VAS scales to assess knee pain severity and patient satisfaction with the surgery. Specified in-hospital data were recorded. Patients were followed up for 12 months. At one year after surgery, there were no statistically significant differences between groups with respect to clinical outcomes and in-hospital data, including operative time, blood loss, hospital length of stay, intraoperative observations, and postoperative complications. Further high-quality investigations of various patient-specific systems and longer follow-up may be helpful in assessing their utility for TKA. PMID:26301241

  7. 2014 ASHG Awards and Addresses

    PubMed Central

    2015-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the presidential address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  8. 2013 ASHG Awards and Addresses

    PubMed Central

    2014-01-01

    Each year at the annual meeting of The American Society of Human Genetics (ASHG), addresses are given in honor of The Society and a number of award winners. A summary of each of these addresses is given below. On the following pages, we have printed the Presidential Address and the addresses for the William Allan Award, the Curt Stern Award, and the Victor A. McKusick Leadership Award. Webcasts of these addresses, as well as those of many other presentations, can be found at http://www.ashg.org.

  9. Circumsporozoite-Specific T Cell Responses in Children Vaccinated with RTS,S/AS01E and Protection against P falciparum Clinical Malaria

    PubMed Central

    Olotu, Ally; Moris, Philippe; Mwacharo, Jedidah; Vekemans, Johan; Kimani, Domtila; Janssens, Michel; Kai, Oscar; Jongert, Erik; Lievens, Marc; Leach, Amanda; Villafana, Tonya; Savarese, Barbara; Marsh, Kevin; Cohen, Joe; Bejon, Philip

    2011-01-01

    Background RTS,S/AS01E is the lead candidate pre-erythrocytic malaria vaccine. In Phase IIb field trials the safety profile was acceptable and the efficacy was 53% (95%CI 31%–72%) for protecting children against clinical malaria caused by P. falciparum. We studied CS-specific T cell responses in order to identify correlates of protection. Methods and Findings We used intracellular cytokine staining (for IL2, IFNγ, and TNFα), ex-vivo ELISPOTs (IFNγ and IL2) and IFNγ cultured ELISPOT assays to characterize the CS-specific cellular responses in 407 children (5–17 months of age) in a phase IIb randomized controlled trial of RTS,S/AS01E (NCT00380393). RTS,S/ AS01E vaccinees had higher frequencies of CS-specific CD4+ T cells producing IFNγ, TNFα or IL2 compared to control vaccinees. In a multivariable analysis TNFα+ CD4+ T cells were independently associated with a reduced risk for clinical malaria among RTS,S/AS01E vaccinees (HR = 0.64, 95%CI 0.49–0.86, p = 0.002). There was a non-significant tendency towards reduced risk among control vaccinees (HR = 0.80, 95%CI 0.62–1.03, p = 0.084), albeit with lower CS-specific T cell frequencies and higher rates of clinical malaria. When data from both RTS,S/AS01E vaccinees and control vaccinees were combined (with adjusting for vaccination group), the HR was 0.74 (95%CI 0.62–0.89, p = 0.001). After a Bonferroni correction for multiple comparisons (n-18), the finding was still significant at p = 0.018. There was no significant correlation between cultured or ex vivo ELISPOT data and protection from clinical malaria. The combination of TNFα+ CD4+ T cells and anti-CS antibody statistically accounted for the protective effect of vaccination in a Cox regression model. Conclusions RTS,S/AS01E induces CS-specific Th1 T cell responses in young children living in a malaria endemic area. The combination of anti-CS antibody concentrations titers and CS-specific TNFα+ CD4+ T cells could account for

  10. 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. PMID:27226436

  11. 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…

  12. 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…

  13. 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…

  14. 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 offered…

  15. Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: correlation with clinical disease stages.

    PubMed

    Rosen, Hugo R; Miner, Camette; Sasaki, Anna W; Lewinsohn, David M; Conrad, Andrew J; Bakke, Antony; Bouwer, H G Archie; Hinrichs, David J

    2002-01-01

    Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, affecting approximately 2% of the world's population. The immune mechanisms responsible for the highly variable natural history in a given individual are unknown. We used a multiparameter flow cytometric technique to functionally and phenotypically characterize HCV-specific effector T cells in the peripheral blood of 32 individuals with different stages of hepatitis C disease (resolved, mild chronic, advanced chronic) and normal controls. We found the highest frequencies of virus-specific effector cells with an activated memory phenotype (CD45RO+CD69+) in subjects who had resolved HCV infection, either spontaneously or with antiviral therapy. Effector cells from patients with resolved infection produced Th1 type cytokines following stimulation with nonstructural antigens (NS3 and NS4), whereas effector cells from chronically infected patients produced Th1 type cytokines predominantly following stimulation with the HCV core antigen. Stimulation with superantigen staphylococcal enterotoxin (SEB) induced the same levels of cytokine production in the different patient groups. Among the HCV-seropositive patients, viral load inversely correlated with the Th1 effector cell response to NS3. Interleukin (IL)-4 was produced only in response to the control antigens, but not in response to the HCV recombinant proteins. Taken together, these findings suggest that a vigorous HCV-specific CD4+ Th1 response, particularly against the nonstructural proteins of the virus, may be associated with viral clearance and protection from disease progression. Prospective studies using this new flow cytometric assay will be required to determine whether antiviral therapy modifies the frequency, specificity, and function of these virus-specific effector cells. PMID:11786976

  16. 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…

  17. Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis.

    PubMed

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

    2014-07-15

    The adoptive transfer of myelin-reactive T cells into wild-type hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem inflammation and ataxia, which characterize disease in IFN-γRKO hosts (atypical EAE). In this article, 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

  18. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone.

    PubMed

    Salido-Guadarrama, Alberto Ivan; Morales-Montor, Jorge Gustavo; Rangel-Escareño, Claudia; Langley, Elizabeth; Peralta-Zaragoza, Oscar; Cruz Colin, Jose Luis; Rodriguez-Dorantes, Mauricio

    2016-06-01

    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 'gray area' (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

  19. Functional Genetic Diversity among Mycobacterium tuberculosis Complex Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival

    PubMed Central

    Homolka, Susanne; Niemann, Stefan; Russell, David G.; Rohde, Kyle H.

    2010-01-01

    Tuberculosis exerts a tremendous burden on global health, with ∼9 million new infections and ∼2 million deaths annually. The Mycobacterium tuberculosis complex (MTC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are more genetically and functionally diverse than appreciated previously. The impact of this natural variation on the virulence and clinical manifestations of the pathogen remains largely unknown. This report examines the effect of genetic diversity among MTC clinical isolates on global gene expression and survival within macrophages. We discovered lineage-specific transcription patterns in vitro and distinct intracellular growth profiles associated with specific responses to host-derived environmental cues. Strain comparisons also facilitated delineation of a core intracellular transcriptome, including genes with highly conserved regulation across the global panel of clinical isolates. This study affords new insights into the genetic information that M. tuberculosis has conserved under selective pressure during its long-term interactions with its human host. PMID:20628579

  20. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

    PubMed

    Singh, Harjeet; Figliola, Matthew J; Dawson, Margaret J; Olivares, Simon; Zhang, Ling; Yang, Ge; Maiti, Sourindra; Manuri, Pallavi; Senyukov, Vladimir; Jena, Bipulendu; Kebriaei, Partow; Champlin, Richard E; Huls, Helen; Cooper, Laurence J N

    2013-01-01

    Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼10(10) T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion. PMID:23741305

  1. Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells

    PubMed Central

    Singh, Harjeet; Figliola, Matthew J.; Dawson, Margaret J.; Olivares, Simon; Zhang, Ling; Yang, Ge; Maiti, Sourindra; Manuri, Pallavi; Senyukov, Vladimir; Jena, Bipulendu; Kebriaei, Partow; Champlin, Richard E.; Huls, Helen; Cooper, Laurence J. N.

    2013-01-01

    Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼1010 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion. PMID:23741305

  2. 21 CFR 20.119 - Lists of names and addresses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Lists of names and addresses. 20.119 Section 20... PUBLIC INFORMATION Availability of Specific Categories of Records § 20.119 Lists of names and addresses. Names and addresses of individuals in Food and Drug Administration records shall not be sold or...

  3. 21 CFR 20.119 - Lists of names and addresses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Lists of names and addresses. 20.119 Section 20... PUBLIC INFORMATION Availability of Specific Categories of Records § 20.119 Lists of names and addresses. Names and addresses of individuals in Food and Drug Administration records shall not be sold or...

  4. 21 CFR 20.119 - Lists of names and addresses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Lists of names and addresses. 20.119 Section 20... PUBLIC INFORMATION Availability of Specific Categories of Records § 20.119 Lists of names and addresses. Names and addresses of individuals in Food and Drug Administration records shall not be sold or...

  5. 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…

  6. Total hip arthroplasty by using a cementless ultrashort stem: a subject-specific finite element analysis for a young patient clinical case.

    PubMed

    Epasto, Gabriella; Foti, Albina; Guglielmino, Eugenio; Rosa, Michele A

    2013-07-01

    In this article, a subject-specific finite element analysis has been developed to study a clinical case of a surgically misaligned hip prosthesis with an ultrashort stem. It was set out to study the strain energy density pattern, comparing the results obtained with computed tomography images. The authors developed two other numerical models: the first one analyzes the stress and strain distributions in the healthy femur (without prosthesis) and the second one analyzes the same boneimplant biomechanical system of the clinical case but assuming the prosthesis in the proper position. The misaligned prosthesis produced an overload at the proximal posterior plane of the femur, as confirmed by computed tomography images, which detect the formation of new bone. The numerical model of the correctly positioned prosthesis demonstrated that the bone is not overloaded and that the position of neutral axis does not significantly shift from the physiological condition. PMID:23636754

  7. 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

  8. Using patient-specific induced pluripotent stem cells to interrogate the pathogenicity of a novel retinal pigment epithelium-specific 65 kDa cryptic splice site mutation and confirm eligibility for enrollment into a clinical gene augmentation trial.

    PubMed

    Tucker, Budd A; Cranston, Cathryn M; Anfinson, Kristin A; Shrestha, Suruchi; Streb, Luan M; Leon, Alejandro; Mullins, Robert F; Stone, Edwin M

    2015-12-01

    Retinal pigment epithelium-specific 65 kDa (RPE65)-associated Leber congenital amaurosis is an autosomal recessive disease that results in reduced visual acuity and night blindness beginning at birth. It is one of the few retinal degenerative disorders for which promising clinical gene transfer trials are currently underway. However, the ability to enroll patients in a gene augmentation trial is dependent on the identification of 2 bona fide disease-causing mutations, and there are some patients with the phenotype of RPE65-associated disease who might benefit from gene transfer but are ineligible because 2 disease-causing genetic variations have not yet been identified. Some such patients have novel mutations in RPE65 for which pathogenicity is difficult to confirm. The goal of this study was to determine if an intronic mutation identified in a 2-year-old patient with presumed RPE65-associated disease was truly pathogenic and grounds for inclusion in a clinical gene augmentation trial. Sequencing of the RPE65 gene revealed 2 mutations: (1) a previously identified disease-causing exonic leucine-to-proline mutation (L408P) and (2) a novel single point mutation in intron 3 (IVS3-11) resulting in an A>G change. RT-PCR analysis using RNA extracted from control human donor eye-derived primary RPE, control iPSC-RPE cells, and proband iPSC-RPE cells revealed that the identified IVS3-11 variation caused a splicing defect that resulted in a frameshift and insertion of a premature stop codon. In this study, we demonstrate how patient-specific iPSCs can be used to confirm pathogenicity of unknown mutations, which can enable positive clinical outcomes. PMID:26364624

  9. Hemodynamics in pulmonary arterial hypertension (PAH): do they explain long-term clinical outcomes with PAH-specific therapy?

    PubMed Central

    2010-01-01

    Background Pulmonary arterial hypertension (PAH) has witnessed dramatic treatment advances over the past decade. However, with the exception of epoprostenol, data from short-term randomized controlled trials (RCTs) have not shown a benefit of these drugs on survival. There remains a need to differentiate between available therapies and current endpoint responses which in turn, could be used to guide treatment selection and provide long-term prognostic information for patients. Methods We performed a systematic literature search of MEDLINE and EMBASE databases for RCTs of PAH-specific therapy published between January 1980 and May 2009. Articles were selected if they contained a placebo comparator and described hemodynamic changes from baseline. We applied the weighted mean change in hemodynamic variables to the equation developed by the National Institutes of Health (NIH) Registry to estimate long-term survival with each therapy. Results Ten RCTs involving 1,635 patients met the inclusion criteria. Suitable hemodynamic data were identified for bosentan, sitaxentan, sildenafil, epoprostenol, beraprost and treprostinil. 77.6% of patients were female and the mean (SD) age was 46.5 ± 4.9 years. 55.5% of patients had idiopathic PAH (iPAH), 23.9% PAH related to connective tissue disease, and 18.2% PAH related to congenital heart disease. Based on the effects observed in short-term trials and, relative to placebo, all analyzed therapies improved survival. The estimated 1-year survival was 78.4%, 77.8%, 76.1%, 75.8%, 75.2%, and 74.1% for epoprostenol, bosentan, treprostinil, sitaxentan, sildenafil, and beraprost, respectively. These estimates are considerably lower than the 1-year observed survival reported in several open-label and registry studies with PAH-specific therapies: 88% - 97%. Conclusion When applied to the NIH Registry equation, hemodynamic changes from baseline appear to underestimate the survival benefits observed with long-term PAH therapy. PMID:20170553

  10. Introduction: the need to address older women's mental health issues.

    PubMed

    Malatesta, Victor J

    2007-01-01

    Women are the primary consumers of mental health services. Ironically, research addressing their unique needs lags behind that of men's issues. The aging process introduces an important variable that accentuates the relative lack of information and specific treatment guidelines for older women who are confronted by mental health problems. This volume offers a comprehensive overview for the health professional who is seeking a greater depth of understanding with respect to the study of mental health problems in general, and how these issues pertain specifically to women and the aging process. A second goal of this project is to provide the practicing therapist and counselor with a research update and a broad clinical perspective offered by seasoned clinicians. Using current psychiatric diagnosis as a framework, the contributions address the range of mental health problems, including dementia and cognitive impairment, schizophrenia, alcohol abuse, mood and anxiety disorders, traumatic and dissociative conditions, sexual and eating disorders, and personality disorders. It is hoped that this book will inform, inspire and encourage students and health professionals in their work with middle aged and older women who are facing mental health challenges. PMID:17588876

  11. 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. PMID:27219506

  12. 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

    Rivero-Buceta, Eva; Sun, Liang; Martínez-Gualda, Belén; Doyagüez, Elisa G; Donckers, Kim; Quesada, Ernesto; Camarasa, María-José; Delang, Leen; San-Félix, Ana; Neyts, Johan; Leyssen, Pieter

    2016-08-01

    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

  13. Photosensitive biosensor array system using optical addressing without an addressing circuit on array biochips

    NASA Astrophysics Data System (ADS)

    Ahn, Chang-Geun; Ah, Chil Seong; Kim, Tae-Youb; Park, Chan Woo; Yang, Jong-Heon; Kim, Ansoon; Sung, Gun Yong

    2010-09-01

    This paper introduces a photosensitive biosensor array system with a simple photodiode array that detects photocurrent changes caused by reactions between probe and target molecules. Using optical addressing, the addressing circuit on the array chip is removed for low-cost application, and real cell addressing is achieved using an externally located computer-controllable light-emitting diode array module. The fabricated biosensor array chip shows a good dynamic range of 1-100 ng/mL under prostate-specific antigen detection, with an on-chip resolution of roughly 1 ng/mL.

  14. Clinically diagnosed insomnia and risk of all-cause and diagnosis-specific disability pension: a nationwide cohort study.

    PubMed

    Jansson, Catarina; Alexanderson, Kristina; Kecklund, Göran; Akerstedt, Torbjörn

    2013-01-01

    Background. Insomnia and disability pension are major health problems, but few population-based studies have examined the association between insomnia and risk of disability pension. Methods. We conducted a prospective nationwide cohort study based on Swedish population-based registers including all 5,028,922 individuals living in Sweden on December 31, 2004/2005, aged 17-64 years, and not on disability or old age pension. Those having at least one admission/specialist visit with a diagnosis of disorders of initiating and maintaining sleep (insomnias) (ICD-10: G47.0) during 2000/2001-2005 were compared to those with no such inpatient/outpatient care. All-cause and diagnosis-specific incident disability pension were followed from 2006 to 2010. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated by Cox regression. Results. In models adjusted for prior sickness absence, sociodemographic factors, and inpatient/specialized outpatient care, associations between insomnia and increased risks of all-cause disability pension (IRR 1.35, 95% CI 1.09-1.67) and disability pension due to mental diagnoses (IRR 1.86, 95% CI 1.38-2.50) were observed. After further adjustment for insomnia medications these associations disappeared. No associations between insomnia and risk of disability pension due to cancer, circulatory, or musculoskeletal diagnoses were observed. Conclusion. Insomnia seems to be positively associated with all-cause disability pension and disability pension due to mental diagnoses. PMID:24490078

  15. Clinically Diagnosed Insomnia and Risk of All-Cause and Diagnosis-Specific Disability Pension: A Nationwide Cohort Study

    PubMed Central

    Alexanderson, Kristina; Kecklund, Göran; Åkerstedt, Torbjörn

    2013-01-01

    Background. Insomnia and disability pension are major health problems, but few population-based studies have examined the association between insomnia and risk of disability pension. Methods. We conducted a prospective nationwide cohort study based on Swedish population-based registers including all 5,028,922 individuals living in Sweden on December 31, 2004/2005, aged 17–64 years, and not on disability or old age pension. Those having at least one admission/specialist visit with a diagnosis of disorders of initiating and maintaining sleep (insomnias) (ICD-10: G47.0) during 2000/2001–2005 were compared to those with no such inpatient/outpatient care. All-cause and diagnosis-specific incident disability pension were followed from 2006 to 2010. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated by Cox regression. Results. In models adjusted for prior sickness absence, sociodemographic factors, and inpatient/specialized outpatient care, associations between insomnia and increased risks of all-cause disability pension (IRR 1.35, 95% CI 1.09–1.67) and disability pension due to mental diagnoses (IRR 1.86, 95% CI 1.38–2.50) were observed. After further adjustment for insomnia medications these associations disappeared. No associations between insomnia and risk of disability pension due to cancer, circulatory, or musculoskeletal diagnoses were observed. Conclusion. Insomnia seems to be positively associated with all-cause disability pension and disability pension due to mental diagnoses. PMID:24490078

  16. Clinical implementation of enhanced dynamic wedges into the Pinnacle treatment planning system: Monte Carlo validation and patient-specific QA

    NASA Astrophysics Data System (ADS)

    Ahmad, Munir; Deng, Jun; Lund, Molly W.; Chen, Zhe; Kimmett, James; Moran, Meena S.; Nath, Ravinder

    2009-01-01

    The goal of this work is to present a systematic Monte Carlo validation study on the clinical implementation of the enhanced dynamic wedges (EDWs) into the Pinnacle3 (Philips Medical Systems, Fitchburg, WI) treatment planning system (TPS) and QA procedures for patient plan verification treated with EDWs. Modeling of EDW beams in the Pinnacle3 TPS, which employs a collapsed-cone convolution superposition (CCCS) dose model, was based on a combination of measured open-beam data and the 'Golden Segmented Treatment Table' (GSTT) provided by Varian for each photon beam energy. To validate EDW models, dose profiles of 6 and 10 MV photon beams from a Clinac 2100 C/D were measured in virtual water at depths from near-surface to 30 cm for a wide range of field sizes and wedge angles using the Profiler 2 (Sun Nuclear Corporation, Melbourne, FL) diode array system. The EDW output factors (EDWOFs) for square fields from 4 to 20 cm wide were measured in virtual water using a small-volume Farmer-type ionization chamber placed at a depth of 10 cm on the central axis. Furthermore, the 6 and 10 MV photon beams emerging from the treatment head of Clinac 2100 C/D were fully modeled and the central-axis depth doses, the off-axis dose profiles and the output factors in water for open and dynamically wedged fields were calculated using the Monte Carlo (MC) package EGS4. Our results have shown that (1) both the central-axis depth doses and the off-axis dose profiles of various EDWs computed with the CCCS dose model and MC simulations showed good agreement with the measurements to within 2%/2 mm; (2) measured EDWOFs used for monitor-unit calculation in Pinnacle3 TPS agreed well with the CCCS and MC predictions within 2%; (3) all the EDW fields satisfied our validation criteria of 1% relative dose difference and 2 mm distance-to-agreement (DTA) with 99-100% passing rate in routine patient treatment plan verification using MapCheck 2D diode array.

  17. Clinical implementation of enhanced dynamic wedges into the Pinnacle treatment planning system: Monte Carlo validation and patient-specific QA.

    PubMed

    Ahmad, Munir; Deng, Jun; Lund, Molly W; Chen, Zhe; Kimmett, James; Moran, Meena S; Nath, Ravinder

    2009-01-21

    The goal of this work is to present a systematic Monte Carlo validation study on the clinical implementation of the enhanced dynamic wedges (EDWs) into the Pinnacle(3) (Philips Medical Systems, Fitchburg, WI) treatment planning system (TPS) and QA procedures for patient plan verification treated with EDWs. Modeling of EDW beams in the Pinnacle(3) TPS, which employs a collapsed-cone convolution superposition (CCCS) dose model, was based on a combination of measured open-beam data and the 'Golden Segmented Treatment Table' (GSTT) provided by Varian for each photon beam energy. To validate EDW models, dose profiles of 6 and 10 MV photon beams from a Clinac 2100 C/D were measured in virtual water at depths from near-surface to 30 cm for a wide range of field sizes and wedge angles using the Profiler 2 (Sun Nuclear Corporation, Melbourne, FL) diode array system. The EDW output factors (EDWOFs) for square fields from 4 to 20 cm wide were measured in virtual water using a small-volume Farmer-type ionization chamber placed at a depth of 10 cm on the central axis. Furthermore, the 6 and 10 MV photon beams emerging from the treatment head of Clinac 2100 C/D were fully modeled and the central-axis depth doses, the off-axis dose profiles and the output factors in water for open and dynamically wedged fields were calculated using the Monte Carlo (MC) package EGS4. Our results have shown that (1) both the central-axis depth doses and the off-axis dose profiles of various EDWs computed with the CCCS dose model and MC simulations showed good agreement with the measurements to within 2%/2 mm; (2) measured EDWOFs used for monitor-unit calculation in Pinnacle(3) TPS agreed well with the CCCS and MC predictions within 2%; (3) all the EDW fields satisfied our validation criteria of 1% relative dose difference and 2 mm distance-to-agreement (DTA) with 99-100% passing rate in routine patient treatment plan verification using MapCheck 2D diode array. PMID:19098353

  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. 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

  20. Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice.

    PubMed

    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

  1. 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

  2. Identification of women at risk of depression in pregnancy: using women's accounts to understand the poor specificity of the Whooley and Arroll case finding questions in clinical practice.

    PubMed

    Darwin, Zoe; McGowan, Linda; Edozien, Leroy C

    2016-02-01

    Antenatal mental health assessment is increasingly common in high-income countries. Despite lacking evidence on validation or acceptability, the Whooley questions (modified PHQ-2) and Arroll 'help' question are used in the UK at booking (the first formal antenatal appointment) to identify possible cases of depression. This study investigated validation of the questions and women's views on assessment. Women (n = 191) booking at an inner-city hospital completed the Whooley and Arroll questions as part of their routine clinical care then completed a research questionnaire containing the Edinburgh postnatal depression scale (EPDS). A purposive subsample (n = 22) were subsequently interviewed. The Whooley questions 'missed' half the possible cases identified using the EPDS (EPDS threshold ≥10: sensitivity 45.7 %, specificity 92.1 %; ≥13: sensitivity 47.8 %, specificity 86.1 %), worsening to nine in ten when adopting the Arroll item (EPDS ≥10: sensitivity 9.1 %, specificity 98.2 %; ≥13: sensitivity 9.5 %, specificity 97.1 %). Women's accounts indicated that under-disclosure relates to the context of assessment and perceived relevance of depression to maternity services. Depression symptoms are under-identified in current local practice. While validated tools are needed that can be readily applied in routine maternity care, psychometric properties will be influenced by the context of disclosure when implemented in practice. PMID:25647071

  3. Magnitude and Complexity of Rectal Mucosa HIV-1-Specific CD8+ T-Cell Responses during Chronic Infection Reflect Clinical Status

    PubMed Central

    Critchfield, J. William; Young, Delandy H.; Hayes, Timothy L.; Braun, Jerome V.; Garcia, Juan C.; Pollard, Richard B.; Shacklett, Barbara L.

    2008-01-01

    Background The intestinal mucosa displays robust virus replication and pronounced CD4+ T-cell loss during acute human immunodeficiency virus type 1 (HIV-1) infection. The ability of HIV-specific CD8+ T-cells to modulate disease course has prompted intensive study, yet the significance of virus-specific CD8+ T-cells in mucosal sites remains unclear. Methods and Findings We evaluated five distinct effector functions of HIVgag-specific CD8+ T-cells in rectal mucosa and blood, individually and in combination, in relationship to clinical status and antiretroviral therapy (ART). In subjects not on ART, the percentage of rectal Gag-specific CD8+ T-cells capable of 3, 4 or 5 simultaneous effector functions was significantly related to blood CD4 count and inversely related to plasma viral load (PVL) (p<0.05). Polyfunctional rectal CD8+ T-cells expressed higher levels of MIP-1β and CD107a on a per cell basis than mono- or bifunctional cells. The production of TNFα, IFN-γ, and CD107a by Gag-specific rectal CD8+ T-cells each correlated inversely (p<0.05) with PVL, and MIP-1β expression revealed a similar trend. CD107a and IFN-γ production were positively related to blood CD4 count (p<0.05), with MIP-1β showing a similar trend. IL-2 production by rectal CD8+ T-cells was highly variable and generally low, and showed no relationship to viral load or blood CD4 count. Conclusions The polyfunctionality of rectal Gag-specific CD8+ T-cells appears to be related to blood CD4 count and inversely related to PVL. The extent to which these associations reflect causality remains to be determined; nevertheless, our data suggest a potentially important role for mucosal T-cells in limiting virus replication during chronic infection. PMID:18974782

  4. 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. PMID:24758452

  5. Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor

    PubMed Central

    Zozio, Thierry; Allix, Caroline; Gunal, Selami; Saribas, Zeynep; Alp, Alpaslan; Durmaz, Riza; Fauville-Dufaux, Maryse; Rastogi, Nalin; Sola, Christophe

    2005-01-01

    Background Population-based bacterial genetics using repeated DNA loci is an efficient approach to study the biodiversity and phylogeographical structure of human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis. Indeed large genetic diversity databases are available for this pathogen and are regularly updated. No population-based polymorphism data were yet available for M. tuberculosis in Turkey, at the crossroads of Eurasia. Results A total of 245 DNAs from Mycobacterium tuberculosis clinical isolates from tuberculosis patients residing in Turkey (Malatya n = 147 or Ankara n = 98) were genotyped by spoligotyping, a high-throughput genotyping method based on the polymorphism of the Direct Repeat locus. Thirty-three spoligotyping-defined clusters including 206 patients and 39 unique patterns were found. The ST41 cluster, as designated according to the international SpolDB3 database project, represented one fourth and when gathered to three genotypes, ST53, ST50 and ST284, one half of all the isolates. Out of 34 clinical isolates harboring ST41 which were further genotyped by IS6110 and by MIRU-VNTR typing, a typical 2-copy IS6110-RFLP pattern and a "215125113322" MIRU-VNTR pattern were observed among 21 clinical isolates. Further search in various databases confirms the likely Turkish-phylogeographical specificity of this clonal complex. Conclusion We described a new phylogeographically-specific clone of M. tuberculosis, designated LAM7-TUR. Further investigations to assess its frequency within all regions of Turkey and its phylogeographical origin and phylogenetic position within the global M. tuberculosis phylogenetic tree will shed new light on its endemicity in Asia Minor. PMID:16045794

  6. Clinical challenges of classification based targeted therapies for non-specific low back pain: What do physiotherapy practitioners and managers think?

    PubMed Central

    Sheeran, Liba; Coales, Philippa; Sparkes, Valerie

    2015-01-01

    Background Classification of non-specific low back pain (NSLBP) was recommended to better target care and so maximise treatment potential. This study investigated physiotherapy practitioners' (PPs) and managers' (PMs) views, experiences and perceptions of barriers and enablers for using classification systems (CSs) to better target treatment for NSLBP in the NHS primary care setting. Design Qualitative focus group and interviews. Methods Data from semi-structured interviews of three PMs and a focus group with five PPs, considered local opinion leaders in physiotherapy, was thematically analysed. Results Five themes emerged (i) CS knowledge: PPs and PMs were aware of CSs and agreed with its usefulness. PPs were mostly aware of CSs informing specific treatments whilst PMs were aware of prognosis based CSs. (ii) Using CSs: PPs classify by experience and clinical reasoning skills, shifting between multiple CSs. PMs were confident that evidence-based practice takes place but believed CSs may not be always used. (iii) Advantages/disadvantages of CSs: Effective targeting of treatments to patients was perceived as advantageous; but the amount of training required was perceived as disadvantageous. (iv) Barriers: Patients' expectations, clinicians' perceptions, insufficiently complex CSs, lack of training resources. (v) Enablers: Development of sufficiently complex CSs, placed within the clinical reasoning process, mentoring, positive engagement with stakeholders and patients. Conclusions PPs and PMs were aware of CSs and agreed with its usefulness. The current classification process was perceived to be largely influenced by individual practitioner knowledge and clinical reasoning skills rather than being based on one CS alone. Barriers and enablers were identified for future research. PMID:25511448

  7. Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72.

    PubMed

    van Blitterswijk, Marka; Gendron, Tania F; Baker, Matthew C; DeJesus-Hernandez, Mariely; Finch, NiCole A; Brown, Patricia H; Daughrity, Lillian M; Murray, Melissa E; Heckman, Michael G; Jiang, Jie; Lagier-Tourenne, Clotilde; Edbauer, Dieter; Cleveland, Don W; Josephs, Keith A; Parisi, Joseph E; Knopman, David S; Petersen, Ronald C; Petrucelli, Leonard; Boeve, Bradley F; Graff-Radford, Neill R; Boylan, Kevin B; Dickson, Dennis W; Rademakers, Rosa

    2015-12-01

    . In the cerebellum, our analysis suggested that transcripts were less likely to be truncated and, excitingly, we discovered that intron containing transcripts were associated with poly(GP) levels [digital molecular barcoding cerebellum (intron 1a): r = 0.33, p = 0.02, and (intron 1b): r = 0.49, p = 0.0004] and poly(GA) levels [digital molecular barcoding cerebellum (intron 1a): r = 0.34, p = 0.02, and (intron 1b): r = 0.38, p = 0.007]. In summary, we report decreased expression of specific C9ORF72 transcripts and provide support for the presence of truncated transcripts as well as pre-mRNAs that may serve as templates for RAN translation. We further show that higher C9ORF72 levels may have beneficial effects, which warrants caution in the development of new therapeutic approaches. PMID:26437865

  8. 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. PMID:23564273

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

    Dumitrescu, Logan; Diggins, Kirsten E; Goodloe, Robert; Crawford, Dana C

    2016-01-01

    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

  14. 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

  15. Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: a preliminary clinical validation.

    PubMed

    Sermesant, M; Chabiniok, R; Chinchapatnam, P; Mansi, T; Billet, F; Moireau, P; Peyrat, J M; Wong, K; Relan, J; Rhode, K; Ginks, M; Lambiase, P; Delingette, H; Sorine, M; Rinaldi, C A; Chapelle, D; Razavi, R; Ayache, N

    2012-01-01

    Cardiac resynchronisation therapy (CRT) is an effective treatment for patients with congestive heart failure and a wide QRS complex. However, up to 30% of patients are non-responders to therapy in terms of exercise capacity or left ventricular reverse remodelling. A number of controversies still remain surrounding patient selection, targeted lead implantation and optimisation of this important treatment. The development of biophysical models to predict the response to CRT represents a potential strategy to address these issues. In this article, we present how the personalisation of an electromechanical model of the myocardium can predict the acute haemodynamic changes associated with CRT. In order to introduce such an approach as a clinical application, we needed to design models that can be individualised from images and electrophysiological mapping of the left ventricle. In this paper the personalisation of the anatomy, the electrophysiology, the kinematics and the mechanics are described. The acute effects of pacing on pressure development were predicted with the in silico model for several pacing conditions on two patients, achieving good agreement with invasive haemodynamic measurements: the mean error on dP/dt(max) is 47.5±35mmHgs(-1), less than 5% error. These promising results demonstrate the potential of physiological models personalised from images and electrophysiology signals to improve patient selection and plan CRT. PMID:21920797

  16. Addressing problems of employee performance.

    PubMed

    McConnell, Charles R

    2011-01-01

    Employee performance problems are essentially of 2 kinds: those that are motivational in origin and those resulting from skill deficiencies. Both kinds of problems are the province of the department manager. Performance problems differ from problems of conduct in that traditional disciplinary processes ordinarily do not apply. Rather, performance problems are addressed through educational and remedial processes. The manager has a basic responsibility in ensuring that everything reasonable is done to help each employee succeed. There are a number of steps the manager can take to address employee performance problems. PMID:21537142

  17. Pathogen group specific risk factors for clinical mastitis, intramammary infection and blind quarters at the herd, cow and quarter level in smallholder dairy farms in Jimma, Ethiopia.

    PubMed

    Tolosa, T; Verbeke, J; Ayana, Z; Piepers, S; Supré, K; De Vliegher, S

    2015-07-01

    A cross-sectional study on clinical mastitis, intramammary infection (IMI) and blind quarters was conducted on 50 smallholder dairy farms in Jimma, Ethiopia. A questionnaire was performed, and quarters of 211 cows were sampled and bacteriologically cultured. Risk factors at the herd, cow, and quarter level for clinical mastitis and (pathogen-specific) intramammary infection were studied using multilevel modeling. As well, factors associated with quarters being blind were studied. Eleven percent of the cows and 4% of the quarters had clinical mastitis whereas 85% of the cows and 51% of the quarters were infected. Eighteen percent of the cows had one or more blind quarter(s), whereas 6% of the quarters was blind. Non-aureus staphylococci were the most frequently isolated pathogens in both clinical mastitis cases and IMI. The odds of clinical mastitis was lower in herds where heifers were purchased in the last year [odds ratio (OR) with 95% confidence interval: 0.11 (0.01-0.90)], old cows (>4 years) [OR: 0.45 (0.18-1.14)], and quarters not showing teat injury [OR: 0.23 (0.07-0.77)]. The odds of IMI caused by any pathogen was higher in herds not practicing teat drying before milking (opposed to drying teats with 1 towel per cow) [OR: 1.68 (1.05-2.69)], cows in later lactation (>180 DIM opposed to ≤90 DIM) [OR: 1.81 (1.14-2.88)], cows with a high (>3) body condition score (BCS) [OR: 1.57 (1.06-2.31)], right quarters (opposed to a left quarter position) [OR: 1.47 (1.10-1.98)], and quarters showing teat injury [OR: 2.30 (0.97-5.43)]. Quarters of cows in herds practicing bucket-fed calf feeding (opposed to suckling) had higher odds of IMI caused by Staphylococcus aureus [OR: 6.05 (1.31-27.90)]. Except for BCS, IMI caused by non-aureus staphylococci was associated with the same risk factors as IMI caused by any pathogen. No access to feed and water immediately after milking [OR: 2.41 (1.26-4.60)], higher parity [OR: 3.60 (1.20-10.82)] and tick infestation [OR: 2.42 (1

  18. 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)

  19. Chemical Address Tags of Fluorescent Bioimaging Probes

    PubMed Central

    Shedden, Kerby; Rosania, Gus R.

    2010-01-01

    Chemical address tags can be defined as specific structural features shared by a set of bioimaging probes having a predictable influence on cell-associated visual signals obtained from these probes. Here, using a large image dataset acquired with a high content screening instrument, machine vision and cheminformatics analysis have been applied to reveal chemical address tags. With a combinatorial library of fluorescent molecules, fluorescence signal intensity, spectral, and spatial features characterizing each one of the probes' visual signals were extracted from images acquired with the three different excitation and emission channels of the imaging instrument. With multivariate regression, the additive contribution from each one of the different building blocks of the bioimaging probes towards each measured, cell-associated image-based feature was calculated. In this manner, variations in the chemical features of the molecules were associated with the resulting staining patterns, facilitating quantitative, objective analysis of chemical address tags. Hierarchical clustering and paired image-cheminformatics analysis revealed key structure-property relationships amongst many building blocks of the fluorescent molecules. The results point to different chemical modifications of the bioimaging probes that can exert similar (or different) effects on the probes' visual signals. Inspection of the clustered structures suggests intramolecular charge migration or partial charge distribution as potential mechanistic determinants of chemical address tag behavior. PMID:20104576

  20. [Use of a program-specific website to disseminate data on antimicrobial susceptibility of clinical isolates from the Tigecycline Evaluation and Surveillance Trial (TEST)].

    PubMed

    Leclercq, R; Goulenok, C; Loncle-Provot, V

    2008-03-01

    Tigecycline Evaluation and Surveillance Trial (TEST) is an international surveillance study designed to assess the in vitro activity of tigecycline and 11 comparators against a range of important clinical pathogens from both the community and the hospital. The updated data obtained from the TEST program are integrated in a database server and available with a web application. The website has been designed to disseminate data collected from the international TEST program to the medical community and has been developed to be user-friendly. The use of this program-specific website can be made in a timely manner to extract antimicrobial resistance data of major microorganisms based on chosen selection criteria. This article describes how to use this web-based program for different analyse-types and the multiple options to display search results. Data can be presented in a table or as a graph or diagram, according to the source of the isolate, type of unit, resistance pattern of the pathogen. The website also allows the user to compare the data of antimicrobial testing at a national or regional level. It provides within a few minutes details on the activity of tigecycline and 11 comparators against clinical isolates collected all around the world. Main results of the TEST program on the in vitro activities of tigecyline against more 65,000 clinical isolates throughout the world are presented. The internet gives infectious diseases specialists and microbiologists the opportunity to have immediate access to continuously updated surveillance data. The TEST website should be helpful to clinicians to better select agents in severe infections, particularly for empirical treatment, that is at a time when the choice of the most appropriate antibiotic is essential for the outcome of the patient. PMID:18276097

  1. Clinically important improvement in the WOMAC and predictor factors for response to non-specific non-steroidal anti-inflammatory drugs in osteoarthritic patients: a prospective study

    PubMed Central

    2012-01-01

    Background The aims of the present study were first to detect MCID for WOMAC in a Moroccan population, and second, to identify the best pre-treatment predictors on the change of health after treatment by non-specific, non-steroidal anti-inflammatory drugs (NSAIDs), and to evaluate whether the predictors were dependent on the choice of the response criterion. Methods The study involved 173 patients with osteoarthritis in whom primary care physicians decided to start treatment with non-selective NSAIDs. Assessments at admission and after 6 weeks were conducted. In order to determine the threshold levels associated with a definition of clinically important improvement, the receiver operating characteristic method was used. Three different measures of response to a 6-week NSAIDs treatment were used: one indirect measure (MCID in the total WOMAC score), one direct measure (transition question) and a combination of both criteria. Results Eighty patients (46.3%) reported "a slightly better" general health status compared to that of 6 weeks before NSAIDs treatment. The MCID proportion is a 16.0% reduction in WOMAC. The most stable pre-treatment predictors on the improvement of health after treatment by NSAIDs were the absence of previous knee injury and a high level of education. Conclusions In our data, a 16.0% reduction of the total WOMAC score from baseline was associated with the highest degree of improvement on the transition scale category. This cut-off point had good accuracy, and should be appropriate for use in the interpretation of clinical studies results, as well as in clinical care. PMID:22269793

  2. 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. PMID:27524055

  3. EGFR protein expression using a specific intracellular domain antibody and PTEN and clinical outcomes in squamous cell lung cancer patients with EGFR-tyrosine kinase inhibitor therapy

    PubMed Central

    Chang, Hyun; Oh, Jisu; Zhang, Xianglan; Kim, Yu Jung; Lee, Jae Ho; Lee, Choon-Taek; Chung, Jin-haeng; Lee, Jong-Seok

    2016-01-01

    Purpose The aim of this research was to examine the molecular and clinical features that are related with EGFR-tyrosine kinase inhibitor (EGFR-TKI) efficacy in previously treated patients with squamous cell carcinoma of the lung (SCCL). Materials and methods This retrospective study included 67 SCCL patients with obtainable lung cancer tissue and records on EGFR-TKI treatment response and survival. EGFR protein expression in lung cancer tissue was measured by immunohistochemistry with a specific antibody that recognizes the intracellular domain (ID) of EGFR. PTEN expression in lung cancer tissue was also evaluated with immunohistochemistry. PI3KCA gene amplification was detected by quantitative real-time polymerase chain reaction, and FGFR1 amplification was assessed by fluorescent in situ hybridization. Results EGFR ID expression (hazard ratio [HR] 0.53, P=0.022) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) (HR 0.43, P=0.022) were significantly related with progression-free survival following EGFR-TKIs treatment. PTEN expression (HR 0.52, P=0.025) was significantly related to overall survival. The group of EGFR-positive or PTEN-positive patients with ECOG PS of 0 or 1 had better clinical outcomes than patients who were EGFR-negative and PTEN-negative or who had poor ECOG PS with longer median progression-free survival (2.1 vs 1.0 months, P=0.05) and overall survival (6.2 vs 2.1 months, P=0.05). Conclusion EGFR expression using an ID-specific antibody and PTEN protein expression may be used to identify SCCL patients who might benefit from EGFR-TKI treatment. PMID:27578983

  4. In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer

    PubMed Central

    Yasuda, Hiroyuki; 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

    2015-01-01

    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. PMID:26515464

  5. 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…

  6. Communities Address Barriers to Connectivity.

    ERIC Educational Resources Information Center

    Byers, Anne

    1996-01-01

    Rural areas lag behind urban areas in access to information technologies. Public institutions play a critical role in extending the benefits of information technologies to those who would not otherwise have access. The most successful rural telecommunications plans address barriers to use, such as unawareness of the benefits, technophobia, the…

  7. 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…

  8. State of the Lab Address

    ScienceCinema

    King, Alex

    2013-03-01

    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.

  9. State of the Lab Address

    SciTech Connect

    King, Alex

    2010-01-01

    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.

  10. Relations of Anxiety Sensitivity, Control Beliefs, and Maternal Over-Control to Fears in Clinic-Referred Children with Specific Phobia

    PubMed Central

    Kane, Elisabeth J; Braunstein, Kara; Ollendick, Thomas H.; Muris, Peter

    2014-01-01

    The relations of fear to anxiety sensitivity, control beliefs, and maternal overprotection were examined in 126 7- to 13-year-old clinically referred children with specific phobias. Results indicated that anxiety sensitivity and control beliefs were significant predictors of children’s fear levels, accounting for approximately 48% of the total variance. Unexpectedly, age, gender, and maternal overprotection did not emerge as significant predictors of fear in the overall sample. In subsequent analyses, anxiety sensitivity was found to be a consistent, significant predictor for both girls and boys, for both younger and older children, and for children with and without an additional anxiety disorder diagnosis. Control beliefs were only a significant predictor for girls, younger children, and children with an additional anxiety diagnosis. Maternal overprotection was not a significant predictor for any group. Children with an additional anxiety disorder diagnosis had higher levels of fear, anxiety sensitivity, and maternal overprotection, as well as lower levels of control beliefs than the non-additional anxiety disorder subgroup. Future directions and clinical implications are explored. PMID:26273182

  11. 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.

  12. A Site-Specific Integrative Plasmid Found in Pseudomonas aeruginosa Clinical Isolate HS87 along with A Plasmid Carrying an Aminoglycoside-Resistant Gene.

    PubMed

    Bi, Dexi; Xie, Yingzhou; Tai, Cui; Jiang, Xiaofei; Zhang, Jie; Harrison, Ewan M; Jia, Shiru; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

    2016-01-01

    Plasmids play critical roles in bacterial fitness and evolution of Pseudomonas aeruginosa. Here two plasmids found in a drug-resistant P. aeruginosa clinical isolate HS87 were completely sequenced. The pHS87b plasmid (11.2 kb) carries phage-related genes and function-unknown genes. Notably, pHS87b encodes an integrase and has an adjacent tRNAThr-associated attachment site. A corresponding integrated form of pHS87b at the tRNAThr locus was identified on the chromosome of P. aeruginosa, showing that pHS87b is able to site-specifically integrate into the 3'-end of the tRNAThr gene. The pHS87a plasmid (26.8 kb) displays a plastic structure containing a putative replication module, stability factors and a variable region. The RepA of pHS87a shows significant similarity to the replication proteins of pPT23A-family plasmids. pHS87a carries a transposon Tn6049, a truncated insertion sequence ΔIS1071 and a Tn402-like class 1 integron which contains an aacA4 cassette that may confer aminoglycoside resistance. Thus, pHS87b is a site-specific integrative plasmid whereas pHS87a is a plastic antibiotic resistance plasmid. The two native plasmids may promote the fitness and evolution of P. aeruginosa. PMID:26841043

  13. 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. PMID:26571130

  14. [Clinical significance of tumor markers in prostatic carcinoma--comparative study of prostatic acid phosphatase, prostate specific antigen and gamma-seminoprotein].

    PubMed

    Yoshiki, T; Okada, K; Oishi, K; Yoshida, O

    1987-12-01

    We measured the prostatic acid phosphatase (PAP), gamma-Seminoprotein (gamma-Sm) and prostate specific antigen (PA) in the serum of 862 patients with various urologic diseases including 89 patients with prostatic cancer. We used a PAP radioimmunoassay kit, gamma-Sm enzyme immunoassay kit, Markit-F-PA enzyme immunoassay kit and PA test Wako enzyme immunoassay kit. Serum PA level in advanced prostatic carcinoma (stage C, D) tended to be higher than that in early stage cancer (stage A, B). The Wako kit gave a higher PA than the Markit-F in each stage. The sensitivity rate of Wako PA test was the highest (81%) of all kits. The specificity rate of PAP was the highest (83%), and the accuracy rate of Markit-F PA was the highest (79%). The positive rate in the combined assay of PAP, gamma-Sm and PA in prostatic cancer was higher than that in the single assay of each tumor marker. We regarded PAP, gamma-Sm and PA as clinically different tumor markers, because their serum level did not correlate definitely. No apparent correlation was found between histopathological grade and the level of each tumor marker. The level of PAP, gamma-Sm and PA in the reactivated patients was significantly higher than that of the well-controlled patients. In the reactivated patients, the positive rate of Markit-F PA was the highest (89%) of all the kits. PMID:2452559

  15. A Site-Specific Integrative Plasmid Found in Pseudomonas aeruginosa Clinical Isolate HS87 along with A Plasmid Carrying an Aminoglycoside-Resistant Gene

    PubMed Central

    Tai, Cui; Jiang, Xiaofei; Zhang, Jie; Harrison, Ewan M.; Jia, Shiru; Deng, Zixin; Rajakumar, Kumar; Ou, Hong-Yu

    2016-01-01

    Plasmids play critical roles in bacterial fitness and evolution of Pseudomonas aeruginosa. Here two plasmids found in a drug-resistant P. aeruginosa clinical isolate HS87 were completely sequenced. The pHS87b plasmid (11.2 kb) carries phage-related genes and function-unknown genes. Notably, pHS87b encodes an integrase and has an adjacent tRNAThr-associated attachment site. A corresponding integrated form of pHS87b at the tRNAThr locus was identified on the chromosome of P. aeruginosa, showing that pHS87b is able to site-specifically integrate into the 3’-end of the tRNAThr gene. The pHS87a plasmid (26.8 kb) displays a plastic structure containing a putative replication module, stability factors and a variable region. The RepA of pHS87a shows significant similarity to the replication proteins of pPT23A-family plasmids. pHS87a carries a transposon Tn6049, a truncated insertion sequence ΔIS1071 and a Tn402-like class 1 integron which contains an aacA4 cassette that may confer aminoglycoside resistance. Thus, pHS87b is a site-specific integrative plasmid whereas pHS87a is a plastic antibiotic resistance plasmid. The two native plasmids may promote the fitness and evolution of P. aeruginosa. PMID:26841043

  16. Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

    PubMed

    Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

    2016-09-01

    The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. PMID:27553466

  17. Hypothyroidism in Clinical Practice

    PubMed Central

    Qari, Faiza

    2014-01-01

    Background: Hypothyroidism is the most common endocrine disease that was seen in the clinical practice especially for family physicians. Methods: This review article covered the important practical clinical issues for managing overt hypothyroidism, subclinical hypothyroidism and hypothyroidism during pregnancy. Conclusions: The clinical issues were addressed by clinical scenario followed by questions and stressed on the important clinical points. PMID:25161963

  18. 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, as well…

  19. OXA-46, a new class D beta-lactamase of narrow substrate specificity encoded by a blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate.

    PubMed

    Giuliani, Francesco; Docquier, Jean-Denis; Riccio, Maria Letizia; Pagani, Laura; Rossolini, Gian Maria

    2005-05-01

    A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a bla(VIM-1) metallo-beta-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D beta-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of Burkholderia cepacia and in unidentified bacteria from a wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in E. coli and purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D beta-lactamases. PMID:15855521

  20. 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. PMID:19637074

  1. 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

  2. A System for Addressing Incidental Findings in Neuroimaging Research

    PubMed Central

    Cramer, Steven C.; Wu, Jennifer; Hanson, Joseph A.; Nouri, Sarvenaz; Karnani, Diraj; Chuang, Tony M.; Le, Vu

    2011-01-01

    When healthy subjects undergo brain imaging, incidental findings are not rare. The optimal response to such findings has been the focus of considerable discussion. The current report describes the operations and results of a system that provides review of incidental findings by an appropriate medical professional. A web-based system was created whereby investigators performing brain MRI scans on healthy subjects could refer images with suspected concerns to a board certified radiologist who had a Certificate of Added Qualification in Neuroradiology. The specific details of this system are described. Among 27 scans suspected by an investigator of having a significant finding, all but one were referred by a researcher with a PhD. The most common concerns described by these investigators were for the possible presence of a cyst or of enlarged ventricles. The most common findings reported by the radiologist were Virchow-Robin spaces and cysts. Findings were generally of low clinical significance, with 1 major exception. Identifying the optimal response to incidental findings in neuroimaging research remains a challenge. The current report describes a system for providing expert assistance and so addresses these issues in the setting of suspected incidental findings. To our knowledge the current system is the first to provide a specific means for evaluation of incidental findings in neuroimaging research. PMID:21224007

  3. 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

  4. 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.

  5. 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.

  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. PMID:25875982

  8. 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

  9. 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.

  10. Global-Address Space Networking (GASNet) Library

    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 spacemore » 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.« less

  11. Characterization of a specific Mycobacterium paratuberculosis recombinant clone expressing 35,000-molecular-weight antigen and reactivity with sera from animals with clinical and subclinical Johne's disease.

    PubMed Central

    El-Zaatari, F A; Naser, S A; Graham, D Y

    1997-01-01

    Johne's disease is a chronic enteritis of ruminants associated with enormous worldwide economic losses for the dairy cow- and goat-rearing industries. Management limitations and eradication programs for this disease have been hampered by the lack of a simple and specific diagnostic test for the detection of subclinical cases. We used a recombinant clone expressing a 35,000-molecular-weight Mycobacterium paratuberculosis antigen (p35 antigen) from a previously constructed expression library of M. paratuberculosis in Escherichia coli. The DNA fragment encoding the p35 gene hybridized only to DNA from Mycobacterium avium complex, but not to DNAs from other mycobacteria and nonmycobacterial organisms. The seroreactivity of p35 was evaluated by immunoblotting against 57 reference serum samples obtained from infected and uninfected animals. p35 was recognized by sera from 100% of animals with advanced Johne's disease (clinical stage) (12 cattle, 2 goats, and 2 sheep) and by sera from 75% of 20 cattle with early infection (subclinical stage). None of the sera from 15 M. paratuberculosis-free cows, 3 Mycobacterium bovis BCG-infected tuberculous cattle, or 3 cows artificially inoculated with multiple doses of viable M. paratuberculosis reacted with p35. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 86, 100, 100, and 75%, respectively. The accuracy of p35 immunoblotting was superior to those of commercially available diagnostic tests for Johne's disease. These results suggest that the p35 recombinant protein has potential for use in the serodiagnosis of animals with Johne's disease at all stages of infection. The DNA fragment encoding p35 may also serve as a probe for identification of M. avium complex infection. PMID:9196196

  12. Interstitial Perfusion Culture with Specific Soluble Factors Inhibits Type I Collagen Production from Human Osteoarthritic Chondrocytes in Clinical-Grade Collagen Sponges.

    PubMed

    Mayer, Nathalie; Lopa, Silvia; 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

  13. Acupoint-specific, frequency-dependent, and improved insulin sensitivity hypoglycemic effect of electroacupuncture applied to drug-combined therapy studied by a randomized control clinical trial.

    PubMed

    Lin, Rong-Tsung; Tzeng, Chung-Yuh; Lee, Yu-Chen; Chen, Ying-I; Hsu, Tai-Hao; Lin, Jaung-Geng; Chang, Shih-Liang

    2014-01-01

    The application of electroacupuncture (EA) to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM). There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz) stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS) activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation. PMID:25024728

  14. Individual differences in the shape bias in preschool children with specific language impairment and typical language development: theoretical and clinical implications.

    PubMed

    Collisson, Beverly Anne; Grela, Bernard; Spaulding, Tammie; Rueckl, Jay G; Magnuson, James S

    2015-05-01

    We investigated whether preschool children with specific language impairment (SLI) exhibit the shape bias in word learning: the bias to generalize based on shape rather than size, color, or texture in an object naming context ('This is a wek; find another wek') but not in a non-naming similarity classification context ('See this? Which one goes with this one?'). Fifty-four preschool children (16 with SLI, 16 children with typical language [TL] in an equated control group, and 22 additional children with TL included in individual differences analyses but not group comparisons) completed a battery of linguistic and cognitive assessments and two experiments. In Experiment 1, children made generalization choices in object naming and similarity classification contexts on separate days, from options similar to a target object in shape, color, or texture. On average, TL children exhibited the shape bias in an object naming context, but children with SLI did not. In Experiment 2, we tested whether the failure to exhibit the shape bias might be linked to ability to detect systematicities in the visual domain. Experiment 2 supported this hypothesis, in that children with SLI failed to learn simple paired visual associations that were readily learned by children with TL. Analyses of individual differences in the two studies revealed that visual paired-associate learning predicted degree of shape bias in children with SLI and TL better than any other measure of nonverbal intelligence or standard assessments of language ability. We discuss theoretical and clinical implications. PMID:25164789

  15. [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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Framework for Address Cooperative Extended Transactions

    1997-12-01

    The Framework for Addressing Cooperative Extended Transactions (FACET) is an object-oriented software framework for building models of complex, cooperative behaviors of agents. it can be used to implement simulation models of societal processes such as the complex interplay of participating individuals and organizations engaged in multiple concurrent transactions in pursuit of their various goals. These transactions can be patterned on, for example, clinical guidelines and procedures, business practices, government and corporate policies, etc. FACET canmore » also address other complex behaviors such as biological life cycles or manufacturing processes. FACET includes generic software objects representing the fundamental classes of agent -- Person and Organization - with mechanisms for resource management, including resolution of conflicting requests for participation and/or use of the agent's resources. The FACET infrastructure supports stochastic behavioral elements and coping mechanisms by which specified special conditions and events can cause an active cooperative process to be preempted, diverting the participants onto appropriate alternative behavioral pathways.« less

  3. 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

  4. Effect of Histological Inflammation on Total and Free Serum Prostate-Specific Antigen Values in Patients Without Clinically Detectable Prostate Cancer

    PubMed Central

    Spajic, Borislav; Reljic, Ante; Katusic, Josip; Popovic, Alek; Grubisic, Igor; Tomas, Davor

    2014-01-01

    Purpose We are often confronted with patients in the "gray zone" (prostate-specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients without prostate cancer (PC). Materials and Methods We studied 106 men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who had no clinical prostatitis. Inflammation observed at biopsies was scored for inflammation type in each biopsy core by use of a four-point scale and was then correlated with tPSA, fPSA, and f/tPSA. Results Different patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type: more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA (p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammation type (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in that the fPSA and f/tPSA were lower in the group with more acute inflammation. Conclusions Subclinical inflammation has a significant influence on fPSA in patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammation is not characterized by elevated tPSA alone but also by a decreased fPSA, a tendency similar to that in PC. PMID:25132947

  5. 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

  6. 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

  7. Addressing Educational Needs of Children with HIV/AIDS.

    ERIC Educational Resources Information Center

    Naude, Hendrina; Pretorius, Etheresia

    2002-01-01

    This paper reviews medical and neuropsychological effects of HIV/AIDS in children and relates these findings specifically to educational difficulties. It then proposes an instructional delivery framework for these children that stresses the importance of addressing their educational needs and includes specific suggestions for reading instruction,…

  8. 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,…

  9. [Prostate specific antigen in patients with prostatic cancer--clinical usefulness of its measurement with sensitive enzyme immunoassay, TOSOH II PA assay].

    PubMed

    Shinka, T; Miyai, M; Sawada, Y; Ohkawa, T

    1994-10-01

    The TOSOH II PA (AIA-PACK PA in the U.S.A.) monoclonal immunoenzyme assay was used and the clinical usefulness of prostate specific antigen (PSA) was evaluated in 39 men with prostatic cancer and 32 men with benign prostatic hyperplasia (BPH) confirmed pathologically. We evaluated the lower limit of detection in this assay by the mean PSA level plue 3 standard deviations in 5 separate experiments with a zero control sera as well as the mean PSA level minus 3 standard deviations in 5 separate experiments with serial dilutions of a known concentration of PSA. PSA concentrations of 0 to 0.25 ng/ml could not be distinguished from the zero control. Therefore, we set the lower limit of detection for the assay as 0.25 ng/ml. At our laboratory, the normal standard value was determined by the mean PSA level plus 3 standard deviations in 79 healthy men as 2.3 ng/ml. Of patients that underwent radical cystoprostatectomy for bladder cancer, all had PSA levels less than 0.25 ng/ml, while only 6% had PAP levels less than 0.11 ng/ml, the lower limit of detection in the TOSOH II PAP assay. We compared TOSOH II PA with Markit PA, a commonly used assay in Japan. Although there was a close linear correlation (r = 0.90) between the TOSOH II PA and Markit PA, the difference of slope in the linear regression lines was great, it was thought due to anti-PSA antibodies in each assay recognizing different epitopes of PSA in the blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7527470

  10. A Systematic Evaluation of Integration Free Reprogramming Methods for Deriving Clinically Relevant Patient Specific Induced Pluripotent Stem (iPS) Cells

    PubMed Central

    Goh, Pollyanna A.; Caxaria, Sara; Casper, Catharina; Rosales, Cecilia; Warner, Thomas T.; Coffey, Pete J.; Nathwani, Amit C.

    2013-01-01

    A systematic evaluation of three different methods for generating induced pluripotent stem (iPS) cells was performed using the same set of parental cells in our quest to develop a feeder independent and xeno-free method for somatic cell reprogramming that could be transferred into a GMP environment. When using the BJ fibroblast cell line, the highest reprogramming efficiency (1.89% of starting cells) was observed with the mRNA based method which was almost 20 fold higher than that observed with the retrovirus (0.2%) and episomal plasmid (0.10%) methods. Standard characterisation tests did not reveal any differences in an array of pluripotency markers between the iPS lines derived using the various methods. However, when the same methods were used to reprogram three different primary fibroblasts lines, two derived from patients with rapid onset parkinsonism dystonia and one from an elderly healthy volunteer, we consistently observed higher reprogramming efficiencies with the episomal plasmid method, which was 4 fold higher when compared to the retroviral method and over 50 fold higher than the mRNA method. Additionally, with the plasmid reprogramming protocol, recombinant vitronectin and synthemax® could be used together with commercially available, fully defined, xeno-free essential 8 medium without significantly impacting the reprogramming efficiency. To demonstrate the robustness of this protocol, we reprogrammed a further 2 primary patient cell lines, one with retinosa pigmentosa and the other with Parkinsons disease. We believe that we have optimised a simple and reproducible method which could be used as a starting point for developing GMP protocols, a prerequisite for generating clinically relevant patient specific iPS cells. PMID:24303062

  11. Gender: addressing a critical focus.

    PubMed

    Thornton, L; Wegner, M N

    1995-01-01

    The definition of gender was addressed at the Fourth World Conference on Women (Beijing, China). After extensive debate, the definition developed by the UN Population Fund in 1995 was adopted: "a set of qualities and behaviors expected from a female or male by society." The sustainability of family planning (FP) programs depends on acknowledgment of the role gender plays in contraceptive decision-making and use. For example, programs must consider the fact that women in many cultures do not make FP decisions without the consent of their spouse. AVSC is examining providers' gender-based ideas about clients and the effects of these views on the quality of reproductive health services. Questions such as how service providers can encourage joint responsibility for contraception without requiring spousal consent or how they can make men feel comfortable about using a male method in a society where FP is considered a woman's issue are being discussed. Also relevant is how service providers can discuss sexual matters openly with female clients in cultures that do not allow women to enjoy their sexuality. Another concern is the potential for physical violence to a client as a result of the provision of FP services. PMID:12294397

  12. 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. PMID:19850183

  13. 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.

  14. Addressing Global Data Sharing Challenges.

    PubMed

    Alter, George C; Vardigan, Mary

    2015-07-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this "uncharted territory," as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  15. Addressing Global Data Sharing Challenges

    PubMed Central

    Alter, George C.

    2015-01-01

    This issue of the Journal of Empirical Research on Human Research Ethics highlights the ethical issues that arise when researchers conducting projects in low- and middle-income countries seek to share the data they produce. Although sharing data is considered a best practice, the barriers to doing so are considerable and there is a need for guidance and examples. To that end, the authors of this article reviewed the articles in this special issue to identify challenges common to the five countries and to offer some practical advice to assist researchers in navigating this “uncharted territory,” as some termed it. Concerns around informed consent, data management, data dissemination, and validation of research contributions were cited frequently as particularly challenging areas, so the authors focused on these four topics with the goal of providing specific resources to consult as well as examples of successful projects attempting to solve many of the problems raised. PMID:26297753

  16. 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.

  17. Clinical pharmacokinetics of meropenem and biapenem in bile and dosing considerations for biliary tract infections based on site-specific pharmacodynamic target attainment.

    PubMed

    Ikawa, Kazuro; Nakashima, Akira; Morikawa, Norifumi; Ikeda, Kayo; Murakami, Yoshiaki; Ohge, Hiroki; Derendorf, Hartmut; Sueda, Taijiro

    2011-12-01

    The present study investigated the pharmacokinetics of meropenem and biapenem in bile and estimated their pharmacodynamic target attainment at the site. Meropenem (0.5 g) or biapenem (0.3 g) was administered to surgery patients (n = 8 for each drug). Venous blood samples and hepatobiliary tract bile samples were obtained at the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo simulation to predict the probability of attaining the pharmacodynamic target (40% of the time above the MIC). Both drugs penetrated similarly into bile, with mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to 0.38 (area under the drug concentration-time curve). The usual regimens of meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions) achieved similar target attainment probabilities in bile (≥ 90%) against Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates. However, against Pseudomonas aeruginosa isolates, meropenem at 1 g q8h and biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively. The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target attainment probability in bile was ≥ 90%) was 1 mg/liter for 0.5 g q8h and 2 mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter for 0.6 g q8h for biapenem. These results help to define the clinical pharmacokinetics of the two carbapenems in bile while also helping to rationalize and optimize the dosing regimens for biliary tract infections based on site-specific pharmacodynamic target attainment. PMID:21947393

  18. Clinical Pharmacokinetics of Meropenem and Biapenem in Bile and Dosing Considerations for Biliary Tract Infections Based on Site-Specific Pharmacodynamic Target Attainment ▿

    PubMed Central

    Ikawa, Kazuro; Nakashima, Akira; Morikawa, Norifumi; Ikeda, Kayo; Murakami, Yoshiaki; Ohge, Hiroki; Derendorf, Hartmut; Sueda, Taijiro

    2011-01-01

    The present study investigated the pharmacokinetics of meropenem and biapenem in bile and estimated their pharmacodynamic target attainment at the site. Meropenem (0.5 g) or biapenem (0.3 g) was administered to surgery patients (n = 8 for each drug). Venous blood samples and hepatobiliary tract bile samples were obtained at the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo simulation to predict the probability of attaining the pharmacodynamic target (40% of the time above the MIC). Both drugs penetrated similarly into bile, with mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to 0.38 (area under the drug concentration-time curve). The usual regimens of meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions) achieved similar target attainment probabilities in bile (≥90%) against Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates. However, against Pseudomonas aeruginosa isolates, meropenem at 1 g q8h and biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively. The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target attainment probability in bile was ≥90%) was 1 mg/liter for 0.5 g q8h and 2 mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter for 0.6 g q8h for biapenem. These results help to define the clinical pharmacokinetics of the two carbapenems in bile while also helping to rationalize and optimize the dosing regimens for biliary tract infections based on site-specific pharmacodynamic target attainment. PMID:21947393

  19. 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.

  20. 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 Central

    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. PMID:26000298

  1. Addressing the vaccine confidence gap.

    PubMed

    Larson, Heidi J; Cooper, Louis Z; Eskola, Juhani; Katz, Samuel L; Ratzan, Scott

    2011-08-01

    Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines. PMID:21664679

  2. 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.

  3. Towards a European Clinical Research Infrastructures Network: the ECRIN programme.

    PubMed

    Demotes-Mainard, Jacques

    2004-01-01

    On the basis of the interconnection of national networks of clinical research centres (CRCs) and clinical trials units (CTUs), the European Clinical Research Infrastructures Network (ECRIN) programme aims to develop an infrastructure allowing for bottom-up harmonisation of the support and training for, and practice of, clinical research, and to provide public sponsors for biotechnology small and medium-sized companies (SMEs) with support for translational research and multicentre clinical studies in Europe. This will be achieved through an application to the next FP6 'Integrated Infrastructure Initiatives' call. However, prior work is required to improve the reciprocal knowledge of partners in the ECRIN consortium and, as a first step, country-specific workshops will be organised by national networks in order to address the organisation of CRC/CTUs and national networks, and their interaction with the national environment of clinical research; this will enable in-depth discussion addressing the bottlenecks hampering transnational studies. PMID:15199684

  4. 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

  5. Vaccine hesitancy: understanding better to address better.

    PubMed

    Kumar, Dewesh; Chandra, Rahul; Mathur, Medha; Samdariya, Saurabh; Kapoor, Neelesh

    2016-01-01

    Vaccine hesitancy is an emerging term in the socio-medical literature which describes an approach to vaccine decision making. It recognizes that there is a continuum between full acceptance and outright refusal of some or all vaccines and challenges the previous understanding of individuals or groups, as being either anti-vaccine or pro-vaccine. The behaviours responsible for vaccine hesitancy can be related to confidence, convenience and complacency. The causes of vaccine hesitancy can be described by the epidemiological triad i.e. the complex interaction of environmental- (i.e. external), agent- (i.e. vaccine) and host (or parent)- specific factors. Vaccine hesitancy is a complex and dynamic issue; future vaccination programs need to reflect and address these context-specific factors in both their design and evaluation. Many experts are of the view that it is best to counter vaccine hesitancy at the population level. They believe that it can be done by introducing more transparency into policy decision-making before immunization programs, providing up-to-date information to the public and health providers about the rigorous procedures undertaken before introduction of new vaccines, and through diversified post-marketing surveillance of vaccine-related events. PMID:26839681

  6. 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. PMID:24837629

  7. The role of protein kinase C-alpha in malignancies of the nervous system and implications for the clinical development of the specific PKC-alpha inhibitor aprinocarsen (Review).

    PubMed

    Lahn, Michael M; Sundell, Karen L; Paterson, Blake M

    2004-02-01

    Antisense oligonucleotide (ASO) technology offers a novel approach for the development of anti-cancer drugs. For example, the ASO aprinocarsen has been developed to specifically inhibit the intracellular signal transduction protein, protein kinase C-alpha (PKC-alpha). The clinical development of such specific or "new targeted" agents in cancer requires a comprehensive understanding of the target protein. This understanding is expected to improve the identification of patients who most likely will benefit from treatment with a specific inhibitor, such as aprinocarsen. In order to better understand the role of PKC-alpha in nervous system malignancies we here review the published literature on PKC-alpha expression in nervous system tumors, including glioblastoma multiforme. In pre-clinical experiments aprinocarsen had demonstrated anti-tumor activity, in particular in animal models of glioblastoma. Thus, clinical study CS10 with aprinocarsen was undertaken in patients with central nervous system (CNS) malignancies. The results of this study and considerations for future clinical studies in CNS tumors are reviewed. PMID:14719093

  8. 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

  9. 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.

  10. 32 CFR 516.7 - Mailing addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. CCCC Chair's Address: Representing Ourselves, 2008

    ERIC Educational Resources Information Center

    Glenn, Cheryl

    2008-01-01

    This article presents the text of the author's address at the fifty-ninth annual convention of the Conference on College Composition and Communication (CCCC) in March 2008. In her address, the author picks up strands of previous Chairs' addresses and weaves them through the fabric of her remarks. What she hopes will give sheen to the fabric is her…

  18. 75 FR 49813 - Change of Address

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... COMMISSION 11 CFR Parts 9405, 9407, 9409, 9410, 9420, and 9428 Change of Address AGENCY: United States... Assistance Commission (EAC) is amending its regulations to reflect a change of address for its headquarters. This technical amendment is a nomenclature change that updates and corrects the address for...

  19. 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...

  20. Site-Specific Clinical Evaluation of the Luminex xTAG Gastrointestinal Pathogen Panel for Detection of Infectious Gastroenteritis in Fecal Specimens

    PubMed Central

    Patel, Anami; Navidad, Jose

    2014-01-01

    We evaluate the clinical performance of the Luminex xTAG gastrointestinal (GI) pathogen in vitro diagnostic (IVD) assay in a comparison between clinical and public health laboratories. The site reproducibility study showed 98.7% sensitivity with high positive and negative agreement values (96.2% and 99.8%, respectively), while assay performance against confirmatory methods resulted in 96.4% sensitivity with similar positive and negative agreement values (90.1% and 99.5%, respectively). High-throughput detection of multiple GI pathogens improved turnaround time, consolidated laboratory workflow, and simplified stool culture practices, thus reducing the overall cost and number of specimens processed. PMID:24899032

  1. Site-specific clinical evaluation of the Luminex xTAG gastrointestinal pathogen panel for detection of infectious gastroenteritis in fecal specimens.

    PubMed

    Patel, Anami; Navidad, Jose; Bhattacharyya, Sanjib

    2014-08-01

    We evaluate the clinical performance of the Luminex xTAG gastrointestinal (GI) pathogen in vitro diagnostic (IVD) assay in a comparison between clinical and public health laboratories. The site reproducibility study showed 98.7% sensitivity with high positive and negative agreement values (96.2% and 99.8%, respectively), while assay performance against confirmatory methods resulted in 96.4% sensitivity with similar positive and negative agreement values (90.1% and 99.5%, respectively). High-throughput detection of multiple GI pathogens improved turnaround time, consolidated laboratory workflow, and simplified stool culture practices, thus reducing the overall cost and number of specimens processed. PMID:24899032

  2. Fine specificity of the antibody response to Epstein-Barr nuclear antigen-2 and other Epstein-Barr virus proteins in patients with clinically isolated syndrome: A peptide microarray-based case-control study.

    PubMed

    Schlemm, Ludwig; Giess, René Markus; Rasche, Ludwig; Pfuhl, Catherina; Wakonig, Katharina; Behrens, Janina Ruth; Scheibenbogen, Carmen; Bellmann-Strobl, Judith; Paul, Friedemann; Reimer, Ulf; Ruprecht, Klemens

    2016-08-15

    We analyzed the fine specificity of antibodies to Epstein-Barr nuclear antigen-2 (EBNA-2) and other Epstein-Barr virus (EBV) proteins in 29 patients with clinically isolated syndrome (CIS, the first clinical manifestation of multiple sclerosis [MS]) and 29 controls with a peptide microarray containing 117 overlapping peptides representing the full-length EBNA-2 protein and 71 peptides from 8 further EBV proteins. While EBV peptide antibodies were elevated in CIS, suggesting that EBV contributes to MS early during disease development, they discriminated groups only slightly better than EBNA-1 antibodies. Thus, the additional value of EBV peptide antibodies as diagnostic biomarkers for CIS appears moderate. PMID:27397076

  3. 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.

  4. Addressing Heart Failure Challenges through Illness-Informed Social Work.

    PubMed

    Hopp, Faith Pratt; Camp, Jessica K; Perry, Tam E

    2015-08-01

    This article describes the role of social workers in addressing the needs of people with heart failure. Although previous studies have explored the role of social workers in health care settings, few studies have addressed the challenges of specific chronic diseases such as heart failure. To address this gap in the literature, this study used qualitative interviews with health care social workers (n = 8) to obtain in-depth information about activities and challenges related to heart failure care. Findings suggest that health care social workers perceive heart failure as characterized by an uncertain illness trajectory, frequent hospitalizations, and difficulties accessing formal and informal care. These findings suggest the importance of what we term illness-informed social work, a practice that combines heart failure knowledge with social work competencies to address the complex psychosocial issues in heart failure care. PMID:26285359

  5. 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

  6. 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

    2013-01-01

    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 Sensors 2013, 13 6688 card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6. PMID:23686145

  7. Using Short Stories to Address Eating Disturbances in Groups

    ERIC Educational Resources Information Center

    Van Lone, Jeffrey S.; Kalodner, Cynthia R.; Coughlin, Janelle W.

    2002-01-01

    Short stories can be an effective group-level intervention for addressing disordered eating attitudes and behaviors. This technique may be used in eating-disorder themed groups or in any group in which members present with eating problems. The authors provide specific guidelines for the use of short stories in group work. An example is provided to…

  8. Racism and the Conspiracy of Silence: Presidential Address

    ERIC Educational Resources Information Center

    Sue, Derald Wing

    2005-01-01

    This presidential address focuses on a specific and daunting assumption about racism that many find disturbing--a belief that no one born and raised in the United States is free from inheriting the racial biases of their forebears. It states explicitly that it is impossible for anyone to not to have racist, sexist, and homophobic attitudes,…

  9. 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…

  10. 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. PMID:23942122

  11. 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

  12. White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

    PubMed Central

    2012-01-01

    There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

  13. Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

    PubMed

    Boch, T; Reinwald, M; Postina, P; Cornely, O A; Vehreschild, J J; Heußel, C P; Heinz, W J; Hoenigl, M; Eigl, S; Lehrnbecher, T; Hahn, J; Claus, B; Lauten, M; Egerer, G; Müller, M C; Will, S; Merker, N; Hofmann, W-K; Buchheidt, D; Spiess, B

    2015-12-01

    The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy. PMID:26497302

  14. 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

  15. Novel Duplicate Address Detection with Hash Function.

    PubMed

    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

  16. 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

  17. 43 CFR 6304.20 - Other uses addressed in special provisions of the Wilderness Act.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... of the Wilderness Act. 6304.20 Section 6304.20 Public Lands: Interior Regulations Relating to Public... (6000) MANAGEMENT OF DESIGNATED WILDERNESS AREAS Uses Addressed in Special Provisions of the Wilderness Act Other Uses Specifically Addressed by the Wilderness Act § 6304.20 Other uses addressed in...

  18. 43 CFR 6304.20 - Other uses addressed in special provisions of the Wilderness Act.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of the Wilderness Act. 6304.20 Section 6304.20 Public Lands: Interior Regulations Relating to Public... (6000) MANAGEMENT OF DESIGNATED WILDERNESS AREAS Uses Addressed in Special Provisions of the Wilderness Act Other Uses Specifically Addressed by the Wilderness Act § 6304.20 Other uses addressed in...

  19. 43 CFR 6304.20 - Other uses addressed in special provisions of the Wilderness Act.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of the Wilderness Act. 6304.20 Section 6304.20 Public Lands: Interior Regulations Relating to Public... (6000) MANAGEMENT OF DESIGNATED WILDERNESS AREAS Uses Addressed in Special Provisions of the Wilderness Act Other Uses Specifically Addressed by the Wilderness Act § 6304.20 Other uses addressed in...

  20. 43 CFR 6304.20 - Other uses addressed in special provisions of the Wilderness Act.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... of the Wilderness Act. 6304.20 Section 6304.20 Public Lands: Interior Regulations Relating to Public... (6000) MANAGEMENT OF DESIGNATED WILDERNESS AREAS Uses Addressed in Special Provisions of the Wilderness Act Other Uses Specifically Addressed by the Wilderness Act § 6304.20 Other uses addressed in...

  1. African American and European American Therapists' Experiences of Addressing Race in Cross-Racial Psychotherapy Dyads

    ERIC Educational Resources Information Center

    Knox, Sarah; Burkard, Alan W.; Johnson, Adanna J.; Suzuki, Lisa A.; Ponterotto, Joseph G.

    2003-01-01

    Using Consensual Qualitative Research, 12 licensed psychologists' overall experiences addressing race in psychotherapy were investigated, as were their experiences addressing race in a specific cross-racial therapy dyad. Results indicated that only African American psychologists reported routinely addressing race with clients of color or when race…

  2. Individual Differences in the Shape Bias in Preschool Children with Specific Language Impairment and Typical Language Development: Theoretical and Clinical Implications

    ERIC Educational Resources Information Center

    Collisson, Beverly Anne; Grela, Bernard; Spaulding, Tammie; Rueckl, Jay G.; Magnuson, James S.

    2015-01-01

    We investigated whether preschool children with specific language impairment (SLI) exhibit the shape bias in word learning: the bias to generalize based on shape rather than size, color, or texture in an object naming context ("This is a wek; find another wek") but not in a non-naming similarity classification context ("See this?…

  3. Clinical Evaluation of Rapid Diagnostic Test Kit Using the Polysaccharide as a Genus-Specific Diagnostic Antigen for Leptospirosis in Korea, Bulgaria, and Argentina

    PubMed Central

    2016-01-01

    Leptospirosis, a zoonotic disease that is caused by many serovars which are more than 200 in the world, is an emerging worldwide disease. Accurate and rapid diagnostic tests for leptospirosis are a critical step to diagnose the disease. There are some commercial kits available for diagnosis of leptospirosis, but the obscurity of a species- or genus-specific antigen of pathogenic Leptospira interrogans causes the reduced sensitivity and specificity. In this study, the polysaccharide derived from lipopolysaccharide (LPS) of nonpathogenic Leptospira biflexa serovar patoc was prepared, and the antigenicity was confirmed by immunoblot and enzyme linked immunosorbent assay (ELISA). The performance of the rapid diagnostic test (RDT) kit using the polysaccharide as a diagnostic antigen was evaluated in Korea, Bulgaria and Argentina. The sensitivity was 93.9%, 100%, and 81.0% and the specificity was 97.9%, 100%, and 95.4% in Korea (which is a rare region occurring with 2 serovars mostly), Bulgaria (epidemic region with 3 serovars chiefly) and Argentina (endemic region with 19 serovars mainly) respectively. These results indicate that this RDT is applicable for global diagnosis of leptospirosis. This rapid and effective diagnosis will be helpful for diagnosis and manage of leptospirosis to use and the polysaccharide of Leptospira may be called as genus specific antigen for diagnosis. PMID:26839470

  4. Clinical Evaluation of Rapid Diagnostic Test Kit Using the Polysaccharide as a Genus-Specific Diagnostic Antigen for Leptospirosis in Korea, Bulgaria, and Argentina.

    PubMed

    Lee, Jin-Woo; Park, Sungman; Kim, Seung Han; Christova, Iva; Jacob, Paulina; Vanasco, Norma B; Kang, Yeon-Mi; Woo, Ye-Ju; Kim, Min Soo; Kim, Young-Jin; Cho, Min-Kee; Kim, Yoon-Won

    2016-02-01

    Leptospirosis, a zoonotic disease that is caused by many serovars which are more than 200 in the world, is an emerging worldwide disease. Accurate and rapid diagnostic tests for leptospirosis are a critical step to diagnose the disease. There are some commercial kits available for diagnosis of leptospirosis, but the obscurity of a species- or genus-specific antigen of pathogenic Leptospira interrogans causes the reduced sensitivity and specificity. In this study, the polysaccharide derived from lipopolysaccharide (LPS) of nonpathogenic Leptospira biflexa serovar patoc was prepared, and the antigenicity was confirmed by immunoblot and enzyme linked immunosorbent assay (ELISA). The performance of the rapid diagnostic test (RDT) kit using the polysaccharide as a diagnostic antigen was evaluated in Korea, Bulgaria and Argentina. The sensitivity was 93.9%, 100%, and 81.0% and the specificity was 97.9%, 100%, and 95.4% in Korea (which is a rare region occurring with 2 serovars mostly), Bulgaria (epidemic region with 3 serovars chiefly) and Argentina (endemic region with 19 serovars mainly) respectively. These results indicate that this RDT is applicable for global diagnosis of leptospirosis. This rapid and effective diagnosis will be helpful for diagnosis and manage of leptospirosis to use and the polysaccharide of Leptospira may be called as genus specific antigen for diagnosis. PMID:26839470

  5. Clinical research in allied health.

    PubMed

    Selker, L G

    1994-01-01

    Allied health professionals in nutrition and medical dietetics, occupational therapy, physical therapy, and speech-language pathology and audiology play both unique and key cross-cutting roles in the furtherance of clinical research. Clinical research in nutrition and medical dietetics uniquely focuses on food nutrient intake and the metabolic utilization of nutrients. Clinical research in occupational therapy has a special focus on the relationship of impairment to disability, the adaptation to disability and the maximization of function. Physical therapy clinical research uniquely targets movement dysfunction and its evaluation and treatment within the context of quality and effective care. Clinical research in speech-language pathology and audiology is singular in its focus on deafness and hearing disorders, voice, speech, language and related disorders, and intersections among these and other neurological and physical conditions. Thus, all of these disciplines are making unique contributions to clinical research. Clinical research in these allied health professions is much more than the above specific foci. Inasmuch as these disciplines are rooted in practice, their contributions to research are inherently clinical. Many, if not most, of these contributions represent further validations of clinical practice or its underlying knowledge base. This means that, at a macro level, clinical research in allied health is very much "applied" research. Within allied health clinical research, this emphasis is redoubled at the "person," or individual level, where considerable attention is given to concepts of function and effectiveness. Clinical research in allied health has played a key cross-cutting role through its emphasis on collaboration. Possibly due to their professional maturation within multidisciplinary academic units, allied health professionals have demonstrated a level of comfort with multidisciplinary and interdisciplinary collaborations unique within many

  6. Content addressable systolic array for sparse matrix computation

    SciTech Connect

    Wing, O.

    1983-01-01

    A systolic array is proposed which is specifically designed to solve a system of sparse linear equations. The array consists of a number of processing elements connected in a ring. Each processing element has its own content addressable memory where the nonzero elements of the sparse matrix are stored. Matrix elements to which elementary operations are applied are extracted from the memory by content addressing. The system of equations is solved in a systolic fashion and the solution is obtained in nz+5n-2 steps where nz is the number of nonzero elements along and below the diagonal and n is the number of equations. 13 references.

  7. 16 CFR 0.2 - Official address.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Official address. 0.2 Section 0.2 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.2 Official address. The principal office of the Commission is at Washington, DC. All communications to...

  8. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS PRIOR NOTICE OF CITIZEN SUITS § 374.6 Addresses. Administrator, U.S. Environmental Protection Agency, 1200...

  9. 10 CFR 218.34 - Addresses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Addresses. 218.34 Section 218.34 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION Procedures § 218.34 Addresses. All..., Economic Regulatory Administration, Department of Energy, 2000 M Street, NW., Washington, DC 20461, and...

  10. 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…

  11. 40 CFR 80.174 - Addresses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Addresses. 80.174 Section 80.174... FUELS AND FUEL ADDITIVES Detergent Gasoline § 80.174 Addresses. (a) The detergent additive sample required under § 80.161(b)(2) shall be sent to: Manager, Fuels and Technical Analysis Group,...

  12. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 11 2014-01-01 2014-01-01 false RUS addresses. 1730.3 Section 1730.3 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain forms referred to in this part...

  13. 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 verb conjugations (Lipski…

  14. 40 CFR 374.6 - Addresses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Addresses. 374.6 Section 374.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS PRIOR NOTICE OF CITIZEN SUITS § 374.6 Addresses. Administrator, U.S. Environmental Protection Agency, 1200...

  15. 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 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...

  16. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 3 2013-07-01 2013-07-01 false Address searches. 674.44 Section 674.44 Education 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...

  17. 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 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...

  18. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 3 2014-07-01 2014-07-01 false Address searches. 674.44 Section 674.44 Education 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...

  19. 34 CFR 674.44 - Address searches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false Address searches. 674.44 Section 674.44 Education 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...

  20. 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.

  1. 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…

  2. Tradition and Change in Swedish Address Forms.

    ERIC Educational Resources Information Center

    Mitchell, Stephen A.

    In most European languages, choice of address form classifies the relation between speakers. The first theoretical framework for analyzing address form usage was established by Brown and Gilman (1960) in their investigation of the semantics of pronoun use in a wide variety of Indo-European languages, which concluded that Europeans use the informal…

  3. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  4. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  5. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  6. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  7. 7 CFR 504.5 - Address.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false Address. 504.5 Section 504.5 Agriculture Regulations... USER FEES § 504.5 Address. Deposits of and requests for microbial patent cultures should be directed to.... University St., Peoria, Illinois 61604; (309) 685-4011....

  8. 25 CFR 2.14 - Record address.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Record address. 2.14 Section 2.14 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROCEDURES AND PRACTICE APPEALS FROM ADMINISTRATIVE ACTIONS § 2.14 Record address. (a) Every interested party who files a document in connection with an...

  9. 25 CFR 2.14 - Record address.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Record address. 2.14 Section 2.14 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROCEDURES AND PRACTICE APPEALS FROM ADMINISTRATIVE ACTIONS § 2.14 Record address. (a) Every interested party who files a document in connection with an...

  10. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    SciTech Connect

    Leana-Cox, J. ); Jenkins, L. ); Palmer, C.G.; Plattner, R. ); Sheppard, L. ); Flejter, W.L. ); Zackowski, J. ); Tsien, F. ); Schwartz, S. )

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  11. Gliadin-Specific T-Cells Mobilized in the Peripheral Blood of Coeliac Patients by Short Oral Gluten Challenge: Clinical Applications

    PubMed Central

    Picascia, Stefania; Mandile, Roberta; Auricchio, Renata; Troncone, Riccardo; Gianfrani, Carmen

    2015-01-01

    Celiac disease (CD) is a common lifelong food intolerance triggered by dietary gluten affecting 1% of the general population. Gliadin-specific T-cell lines and T-cell clones obtained from intestinal biopsies have provided great support in the investigation of immuno-pathogenesis of CD. In the early 2000 a new in vivo, less invasive, approach was established aimed to evaluate the adaptive gliadin-specific T-cell response in peripheral blood of celiac patients on a gluten free diet. In fact, it has been demonstrated that three days of ingestion of wheat-containing food induces the mobilization of memory T lymphocytes reactive against gliadin from gut-associated lymphoid tissue into peripheral blood of CD patients. Such antigen-specific T-cells releasing interferon-γ can be transiently detected by using the enzyme-linked immunospot (ELISPOT) assays or by flow cytometry tetramer technology. This paper discusses the suitability of this in vivo tool to investigate the repertoire of gluten pathogenic peptides, to support CD diagnosis, and to assess the efficacy of novel therapeutic strategies. A systematic review of all potential applications of short oral gluten challenge is provided. PMID:26633487

  12. Clinical Outcomes and Return-to-Sports Participation of 50 Soccer Players After Anterior Cruciate Ligament Reconstruction Through a Sport-Specific Rehabilitation Protocol

    PubMed Central

    Della Villa, Stefano; Boldrini, Lorenzo; Ricci, Margherita; Danelon, Furio; Snyder-Mackler, Lynn; Nanni, Gianni; Roi, Giulio Sergio

    2012-01-01

    Background: Rehabilitation of soccer players after anterior cruciate ligament reconstruction is usually performed without sport-specific guidelines, and the final phases are often left to the team coaches. The possibility of changing this approach has not yet been investigated. Study Design: Case series. Hypothesis: A specific rehabilitation protocol for soccer players, with direct control of the last on-field rehabilitation phases, may lead to complete functional recovery. Methods: Fifty competitive soccer players who followed a sport-specific rehabilitation protocol for soccer were evaluated during the recovery period until their return to competition. The assessment of the functional outcomes was performed using the Knee Outcome Survey–Sports Activity Scale and isokinetic and aerobic fitness tests. Results: The average start of on-field rehabilitation was 90 ± 26 days after surgery; the average time to return to the competitions was 185 ± 52 days. The improvement in the Knee Outcome Survey–Sports Activity Scale during on-field rehabilitation was significant (P < 0.01; from 79 ± 15% to 96 ± 7%). The isokinetic and aerobic fitness tests showed a significant improvement of muscle strength (knee extensors, +55%, P < 0.01; knee flexors, +86%, P < 0.01) and aerobic threshold (+23%, P < 0.01) from the beginning to the end of on-field rehabilitation. Conclusions: Adding on-field rehabilitation to the traditional protocols after anterior cruciate ligament reconstruction may safely lead to complete functional recovery in soccer players. PMID:23016064

  13. Major histocompatibility complex class II dextramers: New tools for the detection of antigen-specific, CD4 T cells in basic and clinical research

    PubMed Central

    Massilamany, Chandirasegaran; Krishnan, Bharathi; Reddy, Jay

    2015-01-01

    The advent of major histocompatibility complex (MHC) tetramer technology has been a major contribution to T cell immunology, because tetramer reagents permit detection of antigen-specific T cells at the single-cell level in heterogeneous populations by flow cytometry. However, unlike MHC class I tetramers, the utility of MHC class II tetramers has been less frequently reported. MHC class II tetramers can be used successfully to enumerate the frequencies of antigen-specific CD4 T cells in cells activated in vitro, but their use for ex vivo analyses continues to be a problem, due in part to their activation dependency for binding with T cells. To circumvent this problem, we recently reported the creation of a new generation of reagents called MHC class II dextramers, which were found to be superior to their counterparts. In this review, we discuss the utility of class II dextramers vis-a-vis tetramers, with respect to their specificity and sensitivity, including potential applications and limitations. PMID:26207337

  14. Training in clinical ethics: launching the clinical ethics immersion course at the Center for Ethics at the Washington Hospital Center.

    PubMed

    Mokwunye, Nneka O; DeRenzo, Evan G; Brown, Virginia A; Lynch, John J

    2012-01-01

    In May 2011, the clinical ethics group of the Center for Ethics at Washington Hospital Center launched a 40-hour, three and one-half day Clinical Ethics Immersion Course. Created to address gaps in training in the practice of clinical ethics, the course is for those who now practice clinical ethics and for those who teach bioethics but who do not, or who rarely, have the opportunity to be in a clinical setting. "Immersion" refers to a high-intensity clinical ethics experience in a busy, urban, acute care hospital. During the Immersion Course, participants join clinical ethicists on working rounds in intensive care units and trauma service. Participants engage in a videotaped role-play conversation with an actor. Each simulated session reflects a practical, realistic clinical ethics case consultation scenario. Participants also review patients' charts, and have small group discussions on selected clinical ethics topics. As ethics consultation requests come into the center, Immersion Course participants accompany clinical ethicists on consultations. Specific to this pilot, because participants' evaluations and course faculty impressions were positive, the Center for Ethics will conduct the course twice each year. We look forward to improving the pilot and establishing the Immersion Course as one step towards addressing the gap in training opportunities in clinical ethics. PMID:22822701

  15. Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome

    PubMed Central

    Alecsandru, D; Valor, L; Sánchez-Ramón, S; Gil, J; Carbone, J; Navarro, J; Rodríguez, J J; Rodríguez-Sainz, C; Fernández-Cruz, E

    2011-01-01

    Recurrent respiratory tract infections (RRTIs) are common clinical conditions in individuals with alterations of the immune function. A prospective open pilot study in a cohort of patients with RRTIs has been performed to assess whether sublingual immunization with a polyvalent bacterial vaccine could exert an immunomodulatory effect on the antigen-specific immunological responses and have an impact on the clinical outcome. Seventeen patients with RRTIs were recruited. An oral polyvalent bacterial preparation (Bactek®) was administered to all patients daily for 6 months. Immunological assessment was performed at baseline and at the end of immunization. Immunological measurements included: T cell-specific proliferations of CD3+CD4+ and CD3+CD8+ to Bactek® antigens, total immunoglobulin levels, antibodies to pneumococcal polysaccharide and tetanus toxoid and B, T and natural killer (NK) cell subsets. There was a significant increase in the proliferative capacity of CD3+CD4+ T cells specific to Bactek® antigens at month 6 in comparison to baseline (P < 0·0001). A significant increase in total CD3+ T cells was also observed (P < 0·05). No significant differences were observed between baseline and month 6 in levels of total immunoglobulins, specific antibodies and B, T or NK cell subsets. A significant reduction in the patient's rate of RRTIs was observed compared with 1 year prior to initiation of therapy (P < 0·0001). The results demonstrate that long-term administration of a sublingual polyvalent bacterial preparation in patients with RRTIs exerts an immune stimulating effect on CD4+ T helper cell responses to bacterial antigens which could be associated with clinical benefit. PMID:21391984

  16. Procoagulant microparticles are increased in patients with Behçet's disease but do not define a specific subset of clinical manifestations.

    PubMed

    Mejía, Juan Carlos; Ortiz, Thaia; Tàssies, Dolors; Solanich, Xavier; Vidaller, Antonio; Cervera, Ricard; Reverter, Joan-Carles; Espinosa, Gerard

    2016-03-01

    Microparticles (MP) are considered a key component in the haemostatic response. Beyond their in vitro procoagulant properties, a number of pieces of evidence points to procoagulant MP as efficient effectors in the haemostatic response and as pathogenic markers of thrombotic disorders and vascular damage. The aim of the present study was to analyze the procoagulant activity of MP and its correlation with clinical manifestations focusing on vascular involvement in patients with Behçet's disease (BD). We analyzed 55 BD patients in inactive phase of the disease (26 men; mean age, 35 ± 15 years) of which 19 had previously suffered from thrombosis (deep venous thrombosis in 17 and ischemic stroke in 2), and 73 healthy controls matched for age and sex. Procoagulant MP were assessed by a functional assay. BD patients showed higher procoagulant MP values than controls (22.89 ± 15.74 nM versus 14.47 ± 7.34 nM; p < 0.0001). Conversely, we did not find differences in the levels of procoagulant MP according to the gender of patients (22.22 ± 16.23 nM for men versus 21.46 ± 16.47 for women; p = 0.846) or to previous and current treatments. Moreover, the plasmatic concentration of MP does not define any clinical phenotype and it was not related to the time of evolution of the disease. Although inactive BD patients had high values of procoagulant MP, they did not differentiate between BD patients with or without thrombosis. PMID:25711877

  17. Milk and Serum J5-Specific Antibody Responses, Milk Production Change, and Clinical Effects following Intramammary Escherichia coli Challenge for J5 Vaccinate and Control Cows▿

    PubMed Central

    Wilson, David J.; Mallard, Bonnie A.; Burton, Jeanne L.; Schukken, Ynte H.; Gröhn, Yrjo T.

    2007-01-01

    Holstein dairy cows (four J5 vaccinates and four controls) selected for no recorded intramammary disease and low somatic cell count (SCC) during the previous lactation were challenged by intramammary infusion of Escherichia coli. Vaccination with J5 was at 8 weeks and again 4 weeks before the anticipated calving date. Cows were challenged at 8 to 16 days in milk (DIM). Shedding of E. coli in milk was significantly higher among controls than vaccinates (no shedding) from 6 h to 21 h postchallenge. From 21 h to 132 h postchallenge, SCC in challenged quarters of controls (5,429,000/ml) was significantly higher than that of vaccinates (490,000/ml). On the day after challenge, milk production in control cows was 8 kg less, while vaccinates gained 0.5 kg, a significant difference. In serum immediately prior to challenge, J5-specific immunoglobulin G1 (IgG1) was significantly higher, IgG2 was nearly significantly higher, and IgM was the same in J5 vaccinates relative to controls. Vaccinates had proportionally more IgG2 in serum postcalving and in the first 12 h following challenge and less IgG2 in milk 24 h after challenge than the controls, approaching statistical significance. The ratio of J5-specific IgG1 and IgG2 combined compared to IgM was significantly higher in vaccinates than in controls in prechallenge serum (ratios of 15.8 and 3.2, respectively) and milk (5.0 and 1.3, respectively). Cows with higher IgM titers in milk 12 h postchallenge produced significantly less milk. Vaccination with J5 was significantly associated with higher production of J5-specific IgG1 and IgG2 in early lactation, reduced SCC, faster clearance of E. coli from milk, and less milk production loss following intramammary challenge. PMID:17460115

  18. Disease Specific Productivity of American Cancer Hospitals

    PubMed Central

    Goldstein, Jeffery A.; Prasad, Vinay

    2015-01-01

    Context Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking. Hypothesis Different institutions are specialized in research of particular diseases. Objective To report disease specific productivity of American cancer hospitals, and propose a summary measure. Method We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and Clinicaltrials.gov for published reports and registrations of clinical trials (respectively) addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure. Results We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list), while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list). Conclusion Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers. PMID:25781329

  19. Strategies intended to address vaccine hesitancy: Review of published reviews.

    PubMed

    Dubé, Eve; Gagnon, Dominique; MacDonald, Noni E

    2015-08-14

    When faced with vaccine hesitancy, public health authorities are looking for effective strategies to address this issue. In this paper, the findings of 15 published literature reviews or meta-analysis that have examined the effectiveness of different interventions to reduce vaccine hesitancy and/or to enhance vaccine acceptance are presented and discussed. From the literature, there is no strong evidence to recommend any specific intervention to address vaccine hesitancy/refusal. The reviewed studies included interventions with diverse content and approaches that were implemented in different settings and targeted various populations. Few interventions were directly targeted to vaccine hesitant individuals. Given the paucity of information on effective strategies to address vaccine hesitancy, when interventions are implemented, planning a rigorous evaluation of their impact on vaccine hesitancy/vaccine acceptance will be essential. PMID:25896385

  20. Development and clinical validation of a real-time PCR assay for PITX2 DNA methylation to predict prostate-specific antigen recurrence in prostate cancer patients following radical prostatectomy.

    PubMed

    Dietrich, Dimo; Hasinger, Oliver; Bañez, Lionel L; Sun, Leon; van Leenders, Geert J; Wheeler, Thomas M; Bangma, Chris H; Wernert, Nicolas; Perner, Sven; Freedland, Stephen J; Corman, John M; Ittmann, Michael M; Lark, Amy L; Madden, John F; Hartmann, Arndt; Schatz, Philipp; Kristiansen, Glen

    2013-03-01

    Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy. PMID:23266319

  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. PMID:16972189

  2. Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

    PubMed Central

    Koga, Michiaki; Kanda, Takashi; Murata, Kenya; Suzuki, Takashi; Kurono, Hiroko; Kunimoto, Masanari; Kaida, Ken-ichi; Mukaino, Akihiro; Sakai, Waka; Maeda, Yasuhiro; Matsuo, Hidenori

    2015-01-01

    Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG. PMID:25790156

  3. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  4. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  5. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  6. 21 CFR 600.2 - Mailing addresses.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... BIOLOGICAL PRODUCTS: GENERAL General Provisions § 600.2 Mailing addresses. (a) Licensed biological products... applications (BLAs) and their amendments and supplements, adverse experience reports, biological product deviation reports, fatality reports, and other correspondence. Biological products samples must not be...

  7. 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 ...

  8. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  9. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  10. 7 CFR 1730.3 - RUS addresses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ELECTRIC SYSTEM OPERATIONS AND MAINTENANCE General § 1730.3 RUS addresses. (a) Persons wishing to obtain... assigned RUS General Field Representative (GFR) or such other office as designated by RUS....

  11. Gender-specific Associations of the Brain-derived Neurotrophic Factor Val66Met Polymorphism with Neurocognitive and Clinical Features in Schizophrenia

    PubMed Central

    Kim, Sung-Wan; Lee, Ju-Yeon; Kang, Hee-Ju; Kim, Seon-Young; Bae, Kyung-Yeol; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang

    2016-01-01

    Objective To explore associations of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with cognitive functioning and psychopathology in patients with schizophrenia. Methods We included 133 subjects meeting the DSM-IV criteria for schizophrenia who were in the post-acute stage of the disease. BDNF Val66Met genotypes were identified via polymerase chain reaction. The computerized neurocognitive function battery, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and Occupational Functioning Scale (SOFAS), and the Subjective Well-being under Neuroleptic Treatment (SWN-K) were administered. Gender-stratified sub-analysis was also conducted to identify gender-specific patterns in the findings. Results In male patients, no significant difference in any measure by BDNF genotype was evident. In female patients, scores on the CDSS and total PANSS and all subscales were significantly higher in valine (Val) carriers. In addition, scores on the SOFAS and SWN-K were significantly lower in Val carriers. In terms of neurocognitive measures, female patients with the Val allele had significantly poorer reaction times and fewer correct responses on the Continuous Performance Test (CPT) and the Trail Making Test (Parts A and B). After adjustment of PANSS total scores and log-transformed CDSS scores, CPT outcomes were significantly poorer in female patients with than in those without the Val allele. Conclusion Gender-specific associations of the Val allele with poor neurocognitive function and more severe psychopathology were evident. Further studies are required to explore the mechanisms of these differences and the potential utility of the BDNF genotype as a predictor of outcome in patients with schizophrenia. PMID:27489381

  12. Nitric Oxide-cGMP Signaling Stimulates Erythropoiesis through Multiple Lineage-Specific Transcription Factors: Clinical Implications and a Novel Target for Erythropoiesis

    PubMed Central

    Ikuta, Tohru; Sellak, Hassan; Odo, Nadine; Adekile, Adekunle D.; Gaensler, Karin M. L.

    2016-01-01

    Much attention has been directed to the physiological effects of nitric oxide (NO)-cGMP signaling, but virtually nothing is known about its hematologic effects. We reported for the first time that cGMP signaling induces human γ-globin gene expression. Aiming at developing novel therapeutics for anemia, we examined here the hematologic effects of NO-cGMP signaling in vivo and in vitro. We treated wild-type mice with NO to activate soluble guanylate cyclase (sGC), a key enzyme of cGMP signaling. Compared to untreated mice, NO-treated mice had higher red blood cell counts and total hemoglobin but reduced leukocyte counts, demonstrating that when activated, NO-cGMP signaling exerts hematopoietic effects on multiple types of blood cells in vivo. We next generated mice which overexpressed rat sGC in erythroid and myeloid cells. The forced expression of sGCs activated cGMP signaling in both lineage cells. Compared with non-transgenic littermates, sGC mice exhibited hematologic changes similar to those of NO-treated mice. Consistently, a membrane-permeable cGMP enhanced the differentiation of hematopoietic progenitors toward erythroid-lineage cells but inhibited them toward myeloid-lineage cells by controlling multiple lineage-specific transcription factors. Human γ-globin gene expression was induced at low but appreciable levels in sGC mice carrying the human β-globin locus. Together, these results demonstrate that NO-cGMP signaling is capable of stimulating erythropoiesis in both in vitro and vivo settings by controlling the expression of multiple lineage-specific transcription factors, suggesting that cGMP signaling upregulates erythropoiesis at the level of gene transcription. The NO-cGMP signaling axis may constitute a novel target to stimulate erythropoiesis in vivo. PMID:26727002

  13. 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

  14. Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [(18)F]Fluspidine-A New Tracer in Clinical Translation for Imaging of σ₁ Receptors.

    PubMed

    Kranz, Mathias; Sattler, Bernhard; Wüst, Nathanael; Deuther-Conrad, Winnie; Patt, Marianne; Meyer, Philipp M; Fischer, Steffen; Donat, Cornelius K; Wünsch, Bernhard; Hesse, Swen; Steinbach, Jörg; Brust, Peter; Sabri, Osama

    2016-01-01

    The enantiomers of [(18)F]fluspidine, recently developed for imaging of σ₁ receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(-)-[(18)F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(-)-[(18)F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [(18)F]fluspidine enantiomers determined from the preclinical studies are comparable with other (18)F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(-)-[(18)F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(-)-[(18)F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies. PMID:27598110

  15. Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers.

    PubMed

    Yuan, Jian-Min; Stepanov, Irina; Murphy, Sharon E; Wang, Renwei; Allen, Sharon; Jensen, Joni; Strayer, Lori; Adams-Haduch, Jennifer; Upadhyaya, Pramod; Le, Chap; Kurzer, Mindy S; Nelson, Heather H; Yu, Mimi C; Hatsukami, Dorothy; Hecht, Stephen S

    2016-05-01

    2-Phenethyl isothiocyanate (PEITC), a natural product found as a conjugate in watercress and other cruciferous vegetables, is an inhibitor of the metabolic activation and lung carcinogenicity of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in F344 rats and A/J mice. We carried out a clinical trial to determine whether PEITC also inhibits the metabolic activation of NNK in smokers. Cigarette smokers were recruited and asked to smoke cigarettes containing deuterium-labeled [pyridine-D4]NNK for an acclimation period of at least 1 week. Then subjects were randomly assigned to one of two arms: PEITC followed by placebo, or placebo followed by PEITC. During the 1-week treatment period, each subject took PEITC (10 mg in 1 mL of olive oil, 4 times per day). There was a 1-week washout period between the PEITC and placebo periods. The NNK metabolic activation ratio [pyridine-D4]hydroxy acid/total [pyridine-D4]NNAL was measured in urine samples to test the hypothesis that PEITC treatment modified NNK metabolism. Eighty-two smokers completed the study and were included in the analysis. Overall, the NNK metabolic activation ratio was reduced by 7.7% with PEITC treatment (P = 0.023). The results of this trial, while modest in effect size, provide a basis for further investigation of PEITC as an inhibitor of lung carcinogenesis by NNK in smokers. Cancer Prev Res; 9(5); 396-405. ©2016 AACR. PMID:26951845

  16. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  17. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  18. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  19. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...

  20. 46 CFR 67.113 - Managing owner designation; address; requirement to report change of address.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Managing owner designation; address; requirement to... Required for Vessel Documentation § 67.113 Managing owner designation; address; requirement to report change of address. The owner of each vessel must designate a managing owner on the Application...